Input: Task: contrast the claim using the given text. Claim: Genetic engineering can extend human life indefinitely without health risks. [SEP] Text: (a) If successful, human germline gene editing may offer heritable “therapeutic treatments of genetic disorders” (Kang et al. , and Fan2016). From a standpoint of health, the benefits of genetic “information manipulation” extend far beyond the “prevention of monogenic diseases” and “personalized assisted reproductive technology” (Ishii, Reference Ishii2017, p. 46). Consider several examples: • Some analysts regard gene editing as a “reliable molecular toolbox” (Bayat et al. , Reference Bayat, Modarressi and Rahimpour2018, p. 107) to “precisely alter genomes for numerous applications” (Batzir et al. , Reference Batzir, Tovin and Hendel2017): from basic research to clinical application, and from developing “animal models for genetic disorders” to “gene therapy to combat virus infectious diseases,” and even to “correct monogenic disorders in vivo or in pluripotent cells” (Huang et al. , Reference Huang, Wang and Zhao2017, p. 3875). • Germline genome editing in human embryos can program cells “for diverse applications, including regenerative medicine and cancer immunotherapy” (Ho & Chen, and Chen2017, p. 57). • It can prevent parents’ giving serious genetic diseases to their offspring (Ishii, Reference Ishii2017, p. 418). It can correct “mutations in patient cells,” and unique gene therapies can screen out causative mutations and identify “rare genetic disorders and non-exonic mutation-caused diseases” (Miyamoto et al. , Reference Miyamoto, Akutsu and Matsuura2018, p. 133). • It can enhance the “efficacy of genome editing in the early embryo” and enable the “generation of allele types previously incompatible with in vivo mutagenesis” (Mianné et al. , Reference Mianné, and Teboul2017, p. 68). [SEP] Justify:

Output: The text contrasts the claim by detailing various applications and potential benefits of genetic engineering, particularly germline gene editing, but it does not support the idea that it can extend human life indefinitely or that there are no health risks involved. The mention of preventing genetic diseases and therapeutic treatments indicates the technology's capabilities, but it doesn't imply that it can extend life indefinitely or do so without health risks, which leaves the claim unsupported.


Input: Task: pass the claim using the given text. Claim: Action potentials are generated by the movement of sodium and potassium ions across the neuron membrane. [SEP] Text: 5) and were visualized offline using a waveform analysis toolbox written by and analyzed with custom scripts written by AO. Briefly, this pipeline of analysis scripts was used to detect and browse evoked glutamate responses, measure voltage response amplitudes and membrane potentials, plot raw recordings and processed data, and perform some statistical analyses. To determine reversal potentials at a given photo-uncaging position, raw response amplitudes were plotted as a function of membrane potential. These data were fit with a linear function (with an R value > 0. 9 in all cases). In some cases, response amplitudes saturated and the linear regression analyses were performed only in the linear range of these data. The x-intercept of the resulting linear function indicated the reversal potential at that position. All electrophysiology analysis scripts are available at the Marder lab GitHub ( Passive cable models Request a detailed protocol A library of equivalent cylinder models was constructed in (freely available at: to simulate apparent reversal potential (Erev) measurements of inhibitory responses generated at positions varying in distance from the recording site. The cables were uniform in their geometric properties: 1000 µm in length and 5 µm in diameter. All cables had a membrane capacitance of 1 µF·cm−2. However, their passive properties were varied combinatorically with four passive conductance (gpas) values (5, 10, 20, and 50 nS/cm2) and five axial resistance (Ra) values (1, 5, 10, 30, 50 Ω·cm). Consequently, each cable can be distinguished by its electrotonic length constant (λ in µm) such that, λ=rRm2Ra where Rm=1gpas. λ values ranged between 200 µm and 5 mm (Figure 11). To measure the apparent Erevs at the 0 µm end of the cable, the membrane potential was manipulated at the recording site with current injections between −8 and +2 nA. An inhibitory current (actual Erev = −70 mV, 𝜏 = 3 ms, gmax = 1, 5, 10, or 50 nS) was activated at sites varying in distance from the recording site (at 0 µm). [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses analysis scripts, reversal potentials, and electrophysiological measurements without mentioning how action potentials are generated or the roles of sodium and potassium ions in this process.


Input: Task: corroborate the claim using the given text. Claim: Small businesses are crucial to local economies and job creation. [SEP] Text: Therefore, any small and medium-scale profit-oriented enterprise, in which the owner has some role to play, not necessarily by fully managing the day-to-day activities of the enterprise, but there exists manifestation of value creation within the production or supply chain of the enterprise, may be considered an entrepreneurial initiative. Poverty is a state of absolute economic deprivation in which the individual cannot independently have access to basic human life-sustaining essentials such as food, clothing, protection, and shelter. Job creation is the income-earning opportunity offered to other people, consciously or unconsciously, in the course of seeking one’s own economic interest for initiating an entrepreneurial activity. Job creation from an entrepreneurial activity could be direct (in which case the entrepreneur personally employs other persons into his/her firm), or indirect (when income-earning opportunities are created for other entrepreneurs to emerge to offer subsidiary products/services) through forward or backward linkages. Income empowerment is the self-confidence, self-esteem, and freedom from servitude associated with earning or the assurance of earning regular income for undertaking a lawful economic activity, which will enable the income earner to live at least a decent normal life. An individual who has been empowered by income should be in a better position to make independent decisions regarding his/her life and be responsible for making these decisions. 2. 2. of Entrepreneurship in In this modern world of globalisation when market-based economic system dominates economic thinking and policy formulation, entrepreneurship, and the development of productive capacities within the private sector have become indispensable to ushering countries into a global trading and stronger development network. In this regard, the benefits of entrepreneurship to an economy in the 21st century cannot be underestimated. To demonstrate the impact of entrepreneurship on employment and income generation which directly reduces economic dependency and poverty, the labour market, showing the changes in labour demand and real wages, a conventional labour market condition has been presented as shown in Figure 1. Within the realm of entrepreneurship, the introduction of new enterprises or the growth of already established entrepreneurial endeavours has the tendency to cause an increase in the demand for labour, since an increasing number of firms and higher wages (from $60 to $90) requires workers to function at optimum as a necessary condition for enterprise expansion. At this point, the profit-oriented entrepreneur Figure 1. Increase in labour demand due to entrepreneurship. [SEP] Justify:

Output: The text corroborates the claim by emphasizing the role of entrepreneurship in job creation and economic growth. It states that entrepreneurship contributes to the increase in labor demand and highlights the importance of new enterprises in creating income-earning opportunities. The discussion on how job creation can be direct or indirect, and its link to empowerment and improved economic conditions, supports the assertion that small businesses significantly impact local economies and employment.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering can extend human life indefinitely without health risks. [SEP] Text: • Personalized, molecular surgeries on “genetic DNA directly target the cause of the disease in a personalized and possibly permanent manner”; they “could be combined with traditional surgery, radiation therapy, or chemo/targeted therapy” (Tang & Schrager, and Schrager2016, p. 83). • By “replacing the mutation-carrying mitochondria of zygotes or oocytes at risk with donated unaffected counterparts,” germline genome editing in human embryos may prevent a “broad range of incurable inborn maladies” caused by mutant mitochondrial DNA (Adashi & Cohen, and Cohen2018). While “no curative treatment for patients with mitochondrial disease” exists, germline gene replacement therapy (unlike prenatal and preimplantation diagnosis) may someday prevent transmission of mitochondrial disease (Amato et al. , Reference Amato, Tachibana, Sparman and Mitalipov2014). • Germline genome editing in human embryos promises a future in which cardiovascular diseases could be “cured by administering a cocktail ofCas9 based therapeutic agents, which functions like a vaccination rather than medications that have to be taken daily” (Li et al. , Reference Li, Song, Liu and Yu2016, p. 193). (b) Now consider a relevant political standpoint: the view that germline manipulation seeks to reduce genetic chance by changing, genetically, unwanted outcomes of the gene pool “lottery” or by precluding such outcomes in the first place, thus “rewrit[ing] the gene pool of future generations” (Cyranoski, Reference Cyranoski2019, p. 440). By reducing the degree to which humans are chance products of sexual reproduction, germline manipulation increases the degree to which the engineers—but neither the engineered nor their descendants—exercise some choice over some of the genetic traits of future human beings. An array of prominent international documents (as well as various ethicists and some scientists) adopt a political viewpoint in claiming that genetic modification harms the future person in their dignity. (One notable exception: the on Bioethics [2018, 2. A critique of genetic essentialism is no strawman Before pursuing my analysis of dignity in part 3, I pause to establish that a critique of genetic essentialism today is hardly a strawman. [SEP] Justify:

Output: The text contrasts the claim by discussing various forms of genetic manipulation and their potential implications, including the ethical considerations and risks associated with germline genome editing. It mentions that while germline gene replacement therapy may prevent certain diseases, there is 'no curative treatment for patients with mitochondrial disease', indicating that genetic engineering does not guarantee indefinite life extension or lack of health risks. Furthermore, the text references the political and ethical debate surrounding genetic modification, suggesting that altering genetic traits raises concerns about dignity and potential harms to future individuals.


Input: Task: pass the claim using the given text. Claim: Action potentials are generated by the movement of sodium and potassium ions across the neuron membrane. [SEP] Text: For a given cable and activation site, the apparent Erev was calculated by plotting the response amplitude (deltaV) as a function of membrane potential at the recording site. For each curve, linear regression analysis was completed (R > 0. 9 and p<0. 01 in all cases). The apparent Erevs were identified as the x-intercept of the linear fit. Figure 11 Download asset Open asset Passive parameters used for cable model library. All pairwise combinations. of passive conductance (gpas; 5, 10, 20, 50 nS/cm2) and axial resistance (Ra; 1, 5, 10,. 30, 50 Ω•cm) values were used to generate a library of 20 cable models with varying. electrotonic length constants (λ; shown numerically and in gray scale, in microns, as grid. elements below) between 220 µm and 5 mm. Add a comment + Open annotations. The current annotation count on this page is being calculated. 2151. PubMed 191. PubMed 9160. PubMed 623. PubMed 367. PubMed 8649. PubMed 13. PubMed 242. PubMed 205. PubMed 855. PubMed 264. PubMed 621. PubMed 723. PubMed 4728. PubMed 2119. PubMed 617. PubMed 6639. PubMed 3754. PubMed 21. PubMed 0877. PubMed 0251. PubMed 1415. PubMed 615. PubMed 1430. PubMed 9306. PubMed 757. PubMed 331. PubMed 504. PubMed 705. PubMed 9156. PubMed 3735. PubMed 529. PubMed 5569. PubMed 1025. PubMed 1207. PubMed 858. PubMed 420. PubMed 12. PubMed 550. PubMed 1209. PubMed 1711. PubMed 1271. PubMed 346. PubMed 3285. PubMed 486. PubMed 375. PubMed 2474. PubMed 266. PubMed 237. PubMed 1177. PubMed 2280. PubMed 532. PubMed 1626. PubMed 903. PubMed 366. PubMed 5621. PubMed 2779. PubMed 1361. PubMed 574. PubMed 163. PubMed 236. PubMed 5548. PubMed 200. [SEP] Justify:

Output: The text does not address the claim regarding action potentials and the movement of sodium and potassium ions across the neuron membrane. It focuses instead on methods for calculating apparent Erev and describes cable models with passive conductance and axial resistance, which is unrelated to the mechanisms of action potentials.


Input: Task: corroborate the claim using the given text. Claim: Small businesses are crucial to local economies and job creation. [SEP] Text: has no room for labour inefficiency otherwise the most cost-efficient automated technology will be acquired to replace the less efficient labour. The initial equilibrium in the labour market occurs at the point where the original labour demand curve intersects the labour supply curve at the pre-entrepreneurial relatively lower wage rate of $60. Entrepreneurship leads to a rise in demand for labour when new entrepreneurial ventures are initiated and as the established firms expand their scope and size of operation. This is indicated by the shift of the demand curve from the red line to dotted green (Figure 1). The new equilibrium is determined by the point where the new demand curve (green dotted line) intersects with the supply curve (blue upward-sloping line). As a consequence, there is an increase in the equilibrium wage rate from $60 to $90 and more direct jobs have been created (1500 new jobs (i. e. , 4500 - 3000)). Once these workers receive real wages above the unemployment compensation rate for their services, they become more economically empowered with a higher chance of escaping poverty. 2. 2. 1. of is about making a difference in business as entrepreneurs would only initiate a business if they are convinced that they have what it takes to seize an opportunity to make a difference in a cause that is vital to their personal and professional ambitions in terms of returns on investment. With this in mind, entrepreneurship is essentially about striving to earn a good living as entrepreneurs are often rewarded with substantial financial gain in the form of profits. Another enviable benefit of entrepreneurship is self-employment and own-bossing, which often offers unlimited job satisfaction and flexibility. Entrepreneurship also creates jobs1 for others and hence could reduce the rates of emigration and unemployment in an economy. Entrepreneurship is a source of income generation that propels economic growth. As entrepreneurs are highly motivated to be competitive and desirous of reaching their full potential because the business is taken as the medium for self-expression and self-actualisation, the production of higher quality goods and services is guaranteed. In this respect, the entrepreneur knows no boundaries as far as business success is concerned because his/her creativity, enthusiasm and vision are limitless. Entrepreneurship also has the potential to enhance the development of new markets as well as the development of entrepreneurial qualities and attitudes among potential entrepreneurs to bring about significant improvements in societies. [SEP] Justify:

Output: The text corroborates the claim by discussing the role of entrepreneurship in creating jobs. It highlights that entrepreneurship leads to a rise in demand for labor as new ventures are initiated, resulting in increased job creation and wages. The mention of 1500 new jobs created as a result of entrepreneurial activities directly supports the idea that small businesses contribute significantly to local economies and job creation.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering can extend human life indefinitely without health risks. [SEP] Text: Even though (a) genetic essentialism is mistaken, (b) it is still widespread and (c) can be dangerous socially, politically, and institutionally. (a) Human genetic essentialism is genetically inaccurate in misconstruing genes as a mechanism of causation along several dimensions. First, it involves reductionism and determinism, obscuring nongenetic factors — including human culture — of human experience and behavior. Second, it misconstrues patterns of human genetic variation by ignoring multifactorial genetics and population thinking, which studies the very small percentage of the human genome containing all genetic differences between any two persons (a mere 0. 1%; see Rosenberg, Reference Rosenberg2011). While genetic essentialism predicts greater variation between any two human groups than within any single group, population thinking demonstrates greater variation within any particular group than among different groups (see Lewontin, Reference Lewontin1972). Third, it does not account for how complex human traits, such as intelligence, are responsive to and conditioned by natural, social, and cultural environments (see Bratsberg & Rogeberg, and Rogeberg2018). Fourth, it misconstrues genetic heritability as an absolute value when, in fact, biological traits result from the entwined vectors of genes, environment, and contingency. Heritability cannot be generalized as a measurable value for all humans (that is, one cannot say that some percentage of a particular trait is determined genetically and the rest, environmentally). Further, specific populations inherit certain traits under specific circumstances. (b) Most biologists and philosophers of biology reject an intrinsic form of genetic essentialism, if by “essentialism” we mean something like “in virtue of what an organism is a member of a certain Linnaean taxon; the issue of what makes an organism a member of that taxon; the issue of the very nature of the taxon” (Devitt, Reference Devitt2008, 3. Against defining dignity in terms of genetic essentialism Genetic essentialism “incorporates a static vision of a human genome that contains only ‘human’ genes that are transmitted vertically from generation to generation” (Charo, Reference Charo2018, p. 348). It rejects the bioengineering of traits that are otherwise unusual in humans. It rejects a genetic engineering that would merely widen the distribution of an already existing trait. [SEP] Justify:

Output: The text contrasts the claim by discussing the misconceptions associated with genetic essentialism and its potential implications for human traits. It emphasizes that genetic heritability is not absolute and that traits are influenced by a combination of genetic, environmental, and cultural factors. This indicates that the assertion of genetic engineering being capable of extending human life indefinitely, without accounting for these complex interactions, is overly simplistic and likely inaccurate.


Input: Task: pass the claim using the given text. Claim: Action potentials are generated by the movement of sodium and potassium ions across the neuron membrane. [SEP] Text: Steady state values for the concentrations of the ions with colours as in ‘A’ (top panel); Vm (middle panel) and volume (bottom panel). The dashed line indicates the default ATPase pump rate used in all simulations unless specified otherwise. The result in ‘B’ was replicated with Hamada et al. ’s experimentally validated model of the ATPase in Figure 1—figure supplement 1B, and the models’ respective pump fluxes are compared in Figure 1—figure supplement 1A. Note that although sufficient Na+/K+-ATPase activity is critical for steady state ionic gradients these variables are relatively stable near the default pump rate (dashed line), Figure 1—figure supplement 2. Figure 1—figure supplement 1 Download asset Open asset Different models of the sodium-potassium ATPase have distinct kinetic properties but produce similar qualitative effects. (A) Comparison of pump rate of different ATPase models against input sodium concentration. The model by Keener and Sneyd (1998) (solid line) is explained in the main paper methods. et al. (2003) method (dashed line) is based on experimental evidence fitted by Hill equations (Hamada et al. , 2003). The simplified equation follows: Jp= Qscale1. 621+6. 7 mMNa+i3+1. 01+67. 6 mMNa+i3, whereQscalewas set such that the same steady state concentration of Na+ ions (and indeed of all ions) was achieved using either model, with units as for P the pump rate constant. (B) Figure 1B was run using the Hamada et al. (2003) model. As for the standard ATPase model, regardless of intracellular starting concentrations of the permeable ions, the model converged to identical steady state values for all parameters without needing to include any means for ‘sensing’ ion concentration, volume or voltage. We show the result for Cl- as a time series of [Cl-]i (top panel) and volume (bottom panel). [SEP] Justify:

Output: The text is irrelevant to the claim, as it primarily discusses the steady-state values of ion concentrations and ATPase models without directly addressing the generation of action potentials or the specific movement of sodium and potassium ions across the neuron membrane. The focus is more on the kinetic properties of different ATPase models and their effects rather than the ionic movements related to action potentials.


Input: Task: corroborate the claim using the given text. Claim: Small businesses are crucial to local economies and job creation. [SEP] Text: Furthermore, entrepreneurship is the key to the growth and development of local industries through the processing of local raw materials into finished and semi-finished goods for domestic and foreign markets. It also promotes the utilisation of improved and cost-effective technology in small and medium-scale enterprises which enhances higher factor productivity at the local level especially in low-income countries where the traditional rural economy is predominant. 2. 2. 2. of the numerous advantages associated with entrepreneurship, there are still some costs that are connected with the profession apparently because entrepreneurship is usually a difficult undertaking with a relatively high failure rate. Some of the potential drawbacks associated with pursuing entrepreneurial ventures include uncertainty of the flow and size of income, working hard for long hours which could even be more than 60 hours per week2, and the risk of losing one’s entire investment. All these impose considerable stress on the entrepreneur. The advantages and disadvantages of entrepreneurship notwithstanding, a rational individual would choose to participate in an economic activity such as becoming an entrepreneur provided, he/she can be certain that the utility of participation exceeds the utility of non-participation. As far as private entrepreneurship is concerned, the pursuit of an entrepreneurial venture is also determined by whether, the individual is oriented towards opportunity-driven entrepreneurship or survival-driven entrepreneurship, which is further, determined by the socioeconomic status of the individual in context as well as his/her entrepreneurial capabilities and attitude towards risk. 2. 3. Entrepreneurship, Employment, Income and Poverty: linkages of entrepreneurship with employment, income, and poverty are quite straightforward even though bi-directional causal relationships are eminent. Development economists opine that economic growth is a necessary pre-condition for poverty reduction, and arguably the single most important factor influencing poverty. This view seems to have enjoyed tremendous universal empirical support as historically there has been a strong negative correlation between per capita income and poverty indicators (see, for instance, Figure 4). Meanwhile, models of economic growth and development have been very consistent in asserting that economic growth is driven primarily by private sector capital accumulation, and hence the economic objective of any modern economy is to promote the conditions that facilitate private sector investment by way of strengthening and motivating the society to develop their entrepreneurial potentials to the optimum. 2. 3. 1. Entrepreneurship and In an entrepreneurial society, job creation is a common feature as new actors in the economy have new characteristics through open-source culture. [SEP] Justify:

Output: The text corroborates the claim by discussing how entrepreneurship drives the growth and development of local industries, leading to job creation. It emphasizes the importance of private sector investment for economic growth and highlights that in an entrepreneurial society, job creation occurs through new economic actors. Therefore, it supports the assertion that small businesses play a critical role in local economies.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering can extend human life indefinitely without health risks. [SEP] Text: Even engineering that brought to expression traits not yet present in the species would compromise the “essential” condition of the human individual and species—although “even traits unfamiliar to us as a species may nonetheless be perfectly consistent with our notion of humans” (Charo, Reference Charo2018, p. 348). In this way, genetic essentialism imagines the integrity of the human species identity without reference to its environment and without reference to time (being beyond space and time is a feature of essentialism in general). With regard to environment: a genetic code is not a guideline for constructing a machine; it cannot predict phenotypic results with any accuracy. That is, “you can’t read the arrangement of the body’s organs in the genome. The information functions as a resource, not a step-by-step guide. To acquire meaning, it must have context: a cell’s history and environment. Tracing how the phenotype emerges from interactions of genes with each other and with their environment is the key puzzle of modern genetics” (Ball, Reference Ball2018, p. 550). Engineering a particular trait in a human embryo does not necessarily lead to the trait’s expression (Ma et al. , Reference Ma, Marti-Gutierrez, Park, Wu, Lee, Suzuki and Mitalipov2017). It can lead to the expression of a trait on the other chromosome, in this way undermining the effort to engineer a child with a particular trait. With regard to time: Genomes are highly changeable. They are also porous with their (always changing) environments. sapiens were genetically engineered to possess capacities not naturally evolved, they would still be Homo sapiens, hence not distant to us in the way that Neanderthals—who were either a different species or a subspecies of our own—are distant to us (even as 1. 5% to 2. 1% of the non-African human populations’ genome has been inherited from Neanderthals). The very idea of the integrity of species identity is misguided because it presupposes a permanent genome. No genome is permanent. A genetic notion of any organism can only be a notion of something that changes over time. Hence a notion of human dignity based on species identity entails somehow suspending the human germline in its current stage of evolution. [SEP] Justify:

Output: The text contrasts the claim by discussing fundamental uncertainties and risks associated with genetic engineering. It emphasizes that a genetic code cannot predict phenotypic results accurately, stating that 'you can’t read the arrangement of the body’s organs in the genome' and that genomes are 'highly changeable'. This implies that the outcomes of genetic engineering can be unpredictable and potentially detrimental, thus challenging the notion that genetic engineering could allow for indefinite life extension without health risks.


Input: Task: corroborate the claim using the given text. Claim: Action potentials are generated by the movement of sodium and potassium ions across the neuron membrane. [SEP] Text: In agreement with experimental results, the slope is non-linear at low [K+]o, which is not seen when using a pure Nernst-potential modelling approach. Figure 2—figure supplement 2 Download asset Open asset K+flux is balanced by active and passive fluxes, dependent on Na+steady states. Varying gNa in the analytical solution caused a reduction in ENa (top panel, pink) and non-zero increases in EK (middle panel, purple). The EK changes with increasing gNa are small because the increased K+ efflux through passive leak membrane channels accompanying membrane depolarisation (bottom panel, solid line) are compensated by increased ATPase K+ influx driven by the Na+ concentration changes (dashed line). KCC2 plays a smaller role (dotted line). Figure 3 with 2 supplements Download asset Open asset Cation-chloride cotransport sets the chloride reversal and driving force for transmembrane chloride flux. (A) Increasing KCC2 activity in our model by increasing gKCC2 from 20 µS/cm2 to 370 µScm2 resulted in a persistent decrease in ECl (green), a minimal decrease in EK (purple), Vm (black) and volume w (bottom panel). This resulted in a permanent increase in the DF for Cl- via a change in ECl from −83. 9 mV to −93. 2 mV (red). (B) The steady state values for ECl, EK, Vm (top panel), volume (middle panel) and Cl- driving force (DF, bottom panel, red) at different KCC2 conductances. Increasing KCC2 activity resulted in a decrease in steady state ECl and an increase in DF. EK represented a lower bound on ECl at high KCC2 conductances. Similar results were noted for other kinetic models of KCC2 (Figure 3—figure supplements 1 and 2). (C) Schematic showing experimental setup. Gramicidin perforated patch-clamp recordings were performed on CA3 pyramidal cells from rat hippocampal organotypic brain slices. (D) Insets depict currents elicited by somatic application (20 ms) of muscimol (10 μM) at different voltages. Calibration: 500 ms, 500 pA. [SEP] Justify:

Output: The text corroborates the claim by discussing the movement of potassium (K+) and sodium (Na+) ions and their effect on the membrane potential, specifically mentioning the role of Na+ steady states and K+ flux. It highlights that the K+ efflux is balanced by active and passive fluxes, which supports the idea that action potentials result from the ionic movements across the neuron membrane.


Input: Task: corroborate the claim using the given text. Claim: Small businesses are crucial to local economies and job creation. [SEP] Text: Such a society breeds a strong network of angel investors and training activities for future venture capitalists and corporate leaders. Besides, entrepreneurial activity is always about value creation. Value creation enhances factor productivity which promotes factor utilisation and intensity in a typical production process. Consequently, jobs are created within and outside a particular enterprise from any entrepreneurial activity. Entrepreneurship increases access to economic opportunities by providing useful information on manpower training and skills development, access to capital, and business development. Through increased knowledge, entrepreneurs can become more competitive in the market. Accordingly, entrepreneurship creates jobs through forward and backward linkages. In a vibrant economy, the development of entrepreneurship breeds the emergence of ancillary enterprises that supply raw materials including energy and related industrial services such as packaging, advertising, insurance, banking, and finance including microfinance, transport, and communication within the supply chain. At the same time, some entrepreneurs may emerge to add value to the by-products generated by the parent firm. 2. 3. 2. Entrepreneurship, Entrepreneurship is very rarely a get-rich-quick business undertaking similar to gambling. Rather, the concept is, in fact, concerned with creating long-term value and consistent cash flow streams for the future through the power of imagination, initiative, and innovation. The long-term value creation focus of entrepreneurship requires that the entrepreneur strategizes towards maximising profits and long-run expansion. Enterprise growth is directly associated with increased demand for productive resources including labour and the payment of realistic and competitive rewards to attract and retain these factor inputs to lend their services to the entrepreneur. In this context, entrepreneurship offers a reliable source of income earning, not only to the entrepreneur and labour, but other factor inputs. Given the long-term focus and the growth potential of entrepreneurial activities, the entrepreneur and labour, and indeed, all income earners from entrepreneurial activities, become more economically independent and confident to confront the challenges of life. It can, therefore, be stated that entrepreneurship promotes income empowerment in an economy. In the modern world, entrepreneurship provides a new approach to fighting poverty and stimulating economic growth in developing countries. Entrepreneurship, to a very large extent, narrows the income gap and delivers a consistent mechanism for earning incomes thereby reducing income inequality and poverty substantially. In practice, entrepreneurship is directly linked to higher productivity. The incentive for higher factor productivity is higher income. [SEP] Justify:

Output: The text corroborates the claim by explaining how entrepreneurship leads to job creation and economic opportunities. It emphasizes that entrepreneurial activities enhance productivity, promote value creation, and consequently, create jobs within and outside enterprises. The text also mentions that entrepreneurship encourages the development of ancillary enterprises that contribute to the economy, all of which supports the idea that small businesses play a vital role in local economies and job creation.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering can extend human life indefinitely without health risks. [SEP] Text: (One wonders: why this stage, rather than any of its past stages or any of its possible future stages? ) Like all evolved organisms, humankind was genetically different in the (distant) past; it will be genetically different in the (distant) future. It will be different naturally in addition to ways it might be different because of biotechnological interventions. Genetic essentialism, as the normative foundation for recognizing human dignity by arresting the human genome at its current stage of evolution, leads to the implausible conclusion that random, natural mutations in humans violate human dignity. (This conclusion might lead to another, equally implausible conclusion: that medical institutions should therefore be required to deploy gene editing to edit out those mutations. ) Or genetic essentialism might entail that a genetic mutation does not violate human dignity because it changes the genome but because the change came about through human intent and agency. Such a conclusion demonizes human agency gratuitously. Not all elite political instruments that invoke a notion of inherent human dignity presuppose genetic essentialism in this sense. Nation’s 1998 on the frames the regulation of possible genetic engineering in terms of human dignity, asserting that “practices which are contrary to human dignity, such as reproductive cloning of human beings, shall not be permitted” (art. 11); that “no research or research applications concerning the human genome … should prevail over respect for the … human dignity of individuals” (art. 10); and that “practices which are contrary to human dignity, such as reproductive cloning of human beings, shall not be permitted” (art. 11). It also recognizes that the “human genome, which by its nature evolves, is subject to mutations” (art. 3)—an assertion that could justify deliberately altering the human genome, at least within some limits. (Reference Andorno2013, p. 89) identifies several ways in which the Declaration on the pursues a notion of dignity, toward regulating human genetic engineering, without practicing essentialism. He reads the Declaration’s claims that the genetic diversity within our species affirms the inherent dignity of all members (preamble), and that the human genome “underlies” the “recognition of their inherent dignity” (art. [SEP] Justify:

Output: The text contrasts the claim by discussing the implications of genetic essentialism and highlighting the complexity of genetic changes, including that natural mutations occur over time and that not all changes to the genome are inherently positive or devoid of health risks. It questions the normative foundation of halting human evolution through genetic engineering and indicates that while genetic mutations can be deliberate, this does not guarantee the absence of health risks, nor does it support the idea that genetic engineering can lead to indefinite human life.


Input: Task: pass the claim using the given text. Claim: Action potentials are generated by the movement of sodium and potassium ions across the neuron membrane. [SEP] Text: Holding current (reflecting membrane current) and total current (reflecting membrane current plus the muscimol-evoked current) were measured at the points indicated by the vertical grey and back lines, respectively. Current-voltage (IV) plots were drawn to calculate changes in and DF before (left) and after (right) furosemide (pink) was applied. Voltages were corrected for series resistance error. (E) Top, population data showing significant changes in EGABA and DF but not Vm five minutes after furosemide application. Bottom, changes in DF over time show a significant decrease from baseline once furosemide was introduced. (F) Meta-analysis of experimental studies demonstrates a correlation between KCC2 activity (% change) and Cl- DF (mV, top plot, red) but not membrane potential (mV, bottom plot, grey), confirming the role of KCC2 for establishing the neuronal Cl- gradient in adult tissue. The data and scoring system used to generate the regression can be found in Supplementary file 2 (Tables S2-1 and S2-2 ‘ns’, non-significant; *p<0. 05; **p<0. 01. The data for ‘C’, ‘D’ and ‘E’ is provided in Figure 3—source data 1. Figure 3—source data 1 Source data for Figure 3C–E. Resting membrane potential, EGABA and driving force at time points as indicated relative to addition of 1 mM furosemide (at time 0 min), for each experiment. Download elife-39575-fig3-data1-v3. xlsx Figure 3—figure supplement 1 Download asset Open asset Models of KCC2 have different kinetic properties. The pump rate velocity for different models of KCC2 were compared for differing intracellular chloride concentration. The equation employed in our model was based on Doyon et al. (2016) (solid line) and is described in the main text. Lewin et al. (2012) (dotted line) used the following equation in their computational model:JKCC2=Jscale ∙ 0. [SEP] Justify:

Output: The text does not address the claim regarding action potentials and their generation through sodium and potassium ion movement. Instead, it discusses measurements related to membrane currents, the effects of furosemide on these currents, and the role of KCC2 in establishing the neuronal Cl- gradient. Hence, it is irrelevant to the stated claim.


Input: Task: corroborate the claim using the given text. Claim: Small businesses are crucial to local economies and job creation. [SEP] Text: The entrepreneur focuses on buying from a lowly-priced market and selling in a highly-priced market for profits over purchases and cost of sales including the cost of transportation, handling, and distribution. Accordingly, the entrepreneurial process begins with good business idea formulation. A good business idea could be the realisation that a new distribution point at a specific location could be a profitable business undertaking. It must be noted that an entrepreneurial activity involves the application of new knowledge through systematic research which culminates in acquiring resources and application of cost-efficient production techniques. By implication, a good business idea in the form of new knowledge must have a commercial value so that this idea can be useful in creating a product or service that is physically different from the resources used to produce it. 3. 3. 1. Review of Empirical studies have shown that owners of SMEs are content with their independence which motivates them to be diligent and generate personal income rather than being an employee for someone else. Organisation (2007) for instance, found that over 85 percent of owners of SMEs were delighted to have owned their own enterprises than working for another person. The influx of entrepreneurial activities has contributed to the springing up of ancillary institutions such as microfinance institutions in recent years. Khandker (2006) in a study of microfinance institutions shows that, indirectly, entrepreneurship is the key to poverty reduction not just for the beneficiaries, but also there are positive externalities to the rest of the society. Coleman (2006) and Hulme (1999) however, argue that the ability of microcredit facilities to eradicate poverty is dependent upon the socioeconomic environment of the household in context. What appears evident is that the application of finance to entrepreneurial activities is a more permanent and reliable way of eradicating poverty in an economy. In more recent studies, Agide and Dada (2023) found that entrepreneurship enhances economic growth as a result of job creation thereby reducing poverty among 18 African countries. Again, Valliere and Peterson (2010) arrived at a similar conclusion for developing countries. These findings are consistent with the conclusion drawn by Wujung and Mbella (2014) in a study involving Cameroon for the period 1980-2013. 3. 2. 3. 2. 1. Entrepreneurship and 1, it is shown that entrepreneurship is synonymous with wealth acquisition. Table 1. 2023 ranking of the world’s richest and their entrepreneurial ventures. [SEP] Justify:

Output: The text corroborates the claim by highlighting that entrepreneurship not only generates personal income but also enhances economic growth through job creation, thus playing a vital role in local economies. Specific references include findings from Agide and Dada (2023), which demonstrate entrepreneurship's impact on job creation and poverty reduction in African countries, supporting the assertion that small businesses are key to local economies.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering can extend human life indefinitely without health risks. [SEP] Text: 1), as invoking the “unity of the human family and the dignity of the human person” not as genetic essentialism but rather as “expressions of philosophical ideals that transcend biology” (Andorno, Reference Andorno2013, p. 89). A notion of dignity that transcends biology does not claim to derive from biology in the manner of genetic essentialism. Hence, “human dignity is not the result of a particular combination of DNA, even of a very complex one” (Andorno, Reference Andorno2013, p. 89). Correspondingly, the Declaration states that inherent human dignity precludes “reduc[ing] individuals to their genetic characteristics” (art. 2). In these ways, among others, the Declaration on the differs from other politically prominent texts such as the United Nations’ 1948 of Human Rights, as well as those from politically prominent organizations such as the Committee and the President’s Council on Bioethics. They attribute human dignity and human rights on the basis of the integrity of human species identity, defined genetically—and not, as Andorno reads the on the symbolically. They invest the human genome with a moral status, treating a biological phenomenon—the genome—as if it were a human artifact. Andorno (Reference Andorno2013) reads the Declaration symbolically as emphasizing the fact that genetic differences among members of the species are negligible from the standpoint of biological identity, that “each individual inherits the same basic genetic structure of those that preceded him or her” such that “genes are common to all past, present and future generations” (p. 89). Andorno reads the Declaration’s appeal to species identity politically. He reads the claim that “everyone has a right to respect for their dignity … regardless of their genetic characteristics” (art. 2) as a claim that all members of the species are equal in terms of worth and dignity. In that spirit, he extrapolates from the words of the text: the Declaration’s “principle of equal value of all human beings does not admit any exception due to predisposition to genetic diseases” (Andorno, Reference Andorno2013, p. 90). [SEP] Justify:

Output: The text contrasts the claim by discussing the philosophical perspectives on human dignity in relation to genetic characteristics. It emphasizes that human dignity does not derive from one's genetic makeup and criticizes the reduction of individuals to their genetic traits. This suggests that there are ethical concerns surrounding genetic engineering, as well as an implication that genetic factors are not the sole determinants of human worth or health, thereby disputing the idea that genetic engineering can provide risk-free, indefinite life extension.


Input: Task: pass the claim using the given text. Claim: Action potentials are generated by the movement of sodium and potassium ions across the neuron membrane. [SEP] Text: (2012) model by increasing Vmax/JScale resulted in a persistent decrease in ECl (green), a minimal decrease in EK (purple), Vm (black) and volume w (bottom panel). This resulted in a permanent increase in the driving force for Cl-. The change in KCC2 strength was matched so that the final shift is similar to the usual shift in driving force gained using our standard KCC2 pump formulation. (B) When the ATPase model of Hamada et al. (2003) was used in the experimental set up in (A) rather than the usual ATPase model, the resulting driving force differed by only 0. 1 mV from the usual value. Figure 4 with 1 supplement Download asset Open asset Adding intracellular or extracellular impermeant anions, without changing the mean charge of impermeant anions, does not affect the steady state gradient or driving force for chloride. (A) Initiating the model with different starting concentrations of intracellular impermeant anions ([X]i) with the same mean charge z = −0. 85 (orange, top panel), led to compensatory volume changes (bottom panel) which resulted in identical steady state concentrations. (B) Steady state ECl (green), EK (purple) and Vm (black) were identical regardless of initial [X]i. Final volume, however, was a linear function of initial [X]i (bottom panel). (C) Addition of impermeant anions of the mean charge (z = −0. 85) caused transients shifts in ECl (green, top panel), EK (purple), Vm (black) as well as [X]i (orange, bottom panel) for the duration of the influx, and sustained increases in volume (black, middle panel). No persistent changes in ECl, EK or Vm were observed. The full time-dependent ionic and water fluxes for the experiment are shown in Figure 4—figure supplement 1, which shows that the inward flux of impermeant anions causes fluxes of all other ions. [SEP] Justify:

Output: The text does not address the claim regarding the generation of action potentials by sodium and potassium ions across the neuron membrane. Instead, it focuses on variations in chloride and potassium ions and the effects of impermeant anions, which are not directly related to the fundamental mechanisms of action potential generation.


Input: Task: corroborate the claim using the given text. Claim: Small businesses are crucial to local economies and job creation. [SEP] Text: Source: Forbes ( (accessed November 20, 2023). From a global point of view, there is a positive correlation between entrepreneurship and wealth. Indeed, all over the world, the richest persons have been entrepreneurs. Examples abound in every community and economy irrespective of the level of development. For instance, in most countries, the richest people of all time have been entrepreneurs who own fleets of marine vessels, aircraft, schools, oil marketing companies, hotels, commercial farms, retail and departmental shops, telecommunication companies, advertising companies, insurance and finance companies, or either engage in extensive import or export business or manufacture/assemble automobiles or computers. This is a clear testimony to the fact that entrepreneurship is the single most important means to create jobs, empower people through increased income, and reduce poverty in an economy. Successful entrepreneurs have generational succession plans and predictable inheritance systems that guarantee their enterprises as a going concern, offering their immediate dependants business opportunities and reliable access to basic needs of life that include good nutrition, decent housing, quality education, healthcare, energy, transportation, entertainment, and philanthropy. 3. 2. 2. in the There has been steady growth in entrepreneurship when measured by the total number of limited liability companies registered and operating in the various countries of the world (Table 2, Chart A). From 27,033,872 in the year 2006, this figure rose by more than 100 percent in 2020, reaching 57598649. 83 despite the devastating effects of COVID-19 on businesses between 2019 and 2020 (Figure 3). The facts presented in Figure 3 buttresses the point that the increasing growth in the number of limited liability companies remains true even when population growth is taken into account. Globally, there has been a steady growth in the annual average business density rate from 42 percent in 2006 to about 75 percent in 2020 (Figure 3, Chart B). 4. Foundation and 4. 1. Foundation 4. 1. 1. Channel to Job Creation, in Low-4, an attempt is made to explain the process of how entrepreneurship can catalyse job creation, income empowerment, and poverty reduction in low-income economies. Within the entrepreneurship ecosystem, it is essential that availability and access to the essential ingredients of entrepreneurship are seen as a necessary condition. [SEP] Justify:

Output: The text corroborates the claim by emphasizing the importance of entrepreneurship in creating jobs and empowering individuals economically. It states that 'entrepreneurship is the single most important means to create jobs, empower people through increased income, and reduce poverty in an economy.' Additionally, it highlights the growth in the number of registered businesses globally despite challenges such as COVID-19, showing that entrepreneurship is vital for local economies.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering can extend human life indefinitely without health risks. [SEP] Text: Andorno also underlines the non-essentializing quality of the Declaration with respect to its discussion of the human genome as a kind of “genetic heritage”: “In a symbolic sense,” the human genome is the “heritage of humanity” (art. 1). The text incorporates the genome, a biological phenomenon, into human culture in terms of a tradition self-consciously handed down within communities as a matter of cultural identity and, as such, something that might be understood by legal metaphor as a kind of collective property that devolves by a (human) right of inheritance. Future generations then appear to be the (quasi-legal) heirs of the current generation’s genome. In this respect, too, the Declaration on the differs from other international instruments and organizations. For example, the 2014 on of the of the Council of Europe states that the “rights to … human dignity protected by … the on human rights imply the right to inherit a genetic pattern which has not been artificially changed” (art. 4). Assembly contrasts a “natural” genome with one artificially modified. Here, human “genetic heritage” is understood not symbolically but biologically. Yet biological heritage (unlike symbolic heritage) is a natural process without normative dimensions. The documents and institutions that invest the human genome with an inherent moral status thereby project a social construct—moral status—onto a natural phenomenon. They practice genetic essentialism by treating the human genome as a cultural heirloom rather than as the product of natural evolution. Evolution has always included the ways in which the human species can “inscribe” itself into natural history. It does so, for example, by artificially selecting plants and animals to breed new species, to alter its own genetic makeup by consuming, for example, milk from cows and sheep and so favoring humans with a mutation that allows for adult lactose tolerance. It does so when aspects of a pregnant woman’s social, material, and psychological environment influences gene expression in the fetal genome. It does so as it steadily becomes a minor coauthor of some of the Earth’s geophysical systems, a phenomenon encapsulated in the theory of the Anthropocene (see Gregg, Reference Gregg, DellaSala and Goldstein2018). [SEP] Justify:

Output: The text contrasts the claim by discussing the distinction between the 'natural' genome and one that is artificially modified. It implies that biological heritage, which includes genetic modifications, does not inherently provide a normative or risk-free status. The text emphasizes the complexities surrounding genetic heritage and essentialism, suggesting that altering the human genome, as genetic engineering does, involves inherent risks and challenges rather than guaranteeing indefinite health or life extension.


Input: Task: pass the claim using the given text. Claim: Action potentials are generated by the movement of sodium and potassium ions across the neuron membrane. [SEP] Text: Steady state ECl, EK, Vm (top panel) and [X]i (middle) increased with increasing z, while changes in z resulted in very small changes in Cl- DF (bottom, red). The vertical dashed line indicates the values at the chosen default z of −0. 85. (C) Influx of a species of impermeant anions with a charge of −1. 5, that decreased the mean charge z (bottom panel) from −0. 85 to −1 and increased the number of impermeant anions also caused persistent decreases of ECl, EK and Vm as in ‘A’, but with larger increases in cell volume (middle panel). Again, very small persistent changes in Cl- DF were observed. The volume changes for different flux amounts and charges are illustrated in Figure 5—figure supplement 1. (D) Top, schematic of the experimental setup where whole-cell recordings were made from CA3 pyramidal cells in mouse organotypic brain slices. Impermeant anions (orange) were delivered via electroporation of the negatively charged fluorescent dextran 488 via a pipette positioned near the soma of the recorded cell. currents were elicited via photo-activation (100 ms, 470 nm LED via objective) of ChR2-expressing GAD2+ interneurons (green cells) in the presence of 5 μM CGP-35348 to block. Lower trace, current clamp recording showing Vm changes during electroporation of anionic dextran. Confocal image demonstrating cell-localized fluorescence of the anionic dextran electroporated in ‘E’. (E) Top, widefield images with electroporation pipette (orange dashed lines) and the recording pipette (white dashed lines). Note increased fluorescence in the soma after electroporation. Below, insets show currents evoked by photo-activation of GAD2+ interneurons at different holding potentials. Calibration: 1 s, 100 pA. Holding current (reflecting membrane current) and total current (reflecting membrane current plus the current) were measured at the points indicated by the vertical grey and black lines, respectively. IV plots were used to calculate and DF before (left) and after (right) electroporation. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses experimental setups and changes in membrane potential due to the introduction of impermeant anions and the effects of photo-activation, without mentioning the movement of sodium and potassium ions specifically related to the generation of action potentials.


Input: Task: corroborate the claim using the given text. Claim: Small businesses are crucial to local economies and job creation. [SEP] Text: The sufficient conditions are the low-income earners taking advantage of the favourable conditions under the ecosystem to engage in vibrant entrepreneurial activities and apply best practices and standards for high entrepreneurial performance in order to realise positive impact on their socioeconomic status. Source: Author based on database and country-specific national statistics bureaux. Figure 3. Magnitudes and trends in total number and density of limited liability companies3. Source: Author’s formulation. Figure 4. A framework of an entrepreneurial approach to job creation, income generation, and poverty reduction in an economy. Table 2 summarises the main components of the determinants of entrepreneurship, entrepreneurial activities, entrepreneurial performance, and socioeconomic impact of entrepreneurship as elements of an entrepreneurial process relevant to job creation, income generation and empowerment, and poverty reduction in a typical economy. Access to capital, attitudes to work and risk as well as investment culture, training, research and development (R&D) and technology, quality of entrepreneurial resources which includes special institutional support services such as business incubators and accelerators, sociopolitical and economic environment, legal and regulatory framework, and government policy are the essential factors influencing the development of entrepreneurship in an economy. Entrepreneurial activities include the identification/creation of business opportunities, evaluation of business ideas/opportunities, business planning, mobilisation of requisite resources, self-involvement/self-employment such as management of the enterprise, and combination of the resources through innovative practices, value addition, and supply chain activities. Concerning the performance of an entrepreneurial accomplishment, the survival rate of the enterprise, growth of the enterprise, labour force, turnover, and domestic market dominance, penetration of external markets, profit margins, enterprise risk management (ERM) which should include generational succession plan, and tax and other statutory compliance are the key issues involved. In examining the socioeconomic impact of entrepreneurship in an economy, the critical factors often taken into account include job creation, income status of employees and the entrepreneur, level of consumption, rate of saving and investment, overall reduction in poverty levels of employees and the entrepreneur, Table 2. Elements of entrepreneurship in job creation, income empowerment and poverty reduction. Source: Author’s own compilation. +Risk Management. contribution to the growth process of the economy as well as the direct contribution to community development through infrastructural development and corporate social responsibility. 4. 2. [SEP] Justify:

Output: The text corroborates the claim by emphasizing the importance of entrepreneurial activities in job creation and socioeconomic development. It discusses how entrepreneurship leads to the identification of business opportunities, which is fundamental for job creation and income generation. Additionally, it outlines various factors that influence entrepreneurship, indicating its critical role in not only creating jobs but also contributing to the overall growth of the economy and community development.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering can extend human life indefinitely without health risks. [SEP] Text: But the assertion by international instruments and organizations of a kind of species’ “ownership” of its own genome—ownership in the cultural sense of declaring prohibitions on certain ways of treating it biotechnologically, toward preserving it from objectionable forms of manipulation—essentializes culturally what is, after all, a phenomenon of natural contingency. In a third way as well, Andorno reads the Declaration on the in a manner that is non-essentialist. notes that the human genome “by its nature evolves” and “is subject to mutations” (art. 3). From this recognition of changes to the human genome that occur in the very long term via mutation, Andorno (Reference Andorno2013) finds it “appropriate to consider the human genome as a ‘common heritage of humanity’ and therefore to protect it from irresponsible manipulations” (p. 89). Heritage so understood entails not the essentialist responsibility to preserve a genome construed as having inherent qualities, but the cultural responsibility of present generations toward future ones in the sense of human stewardship of life on Earth. differs from the 1997 Convention for the Protection of and Dignity of the with Regard to the Application of Biology and Medicine. states that the abuse of human germline genetic engineering “may endanger not only the individual but also the species itself” (art. 13). Its declares the “need to respect the human being both as an individual and as a member of the human species” and to recognize the “importance of ensuring the dignity of the human being” (preamble). According to Charo (Reference Charo2018), the is the “most salient instrument on human rights in the biomedical field” (p. 345). It connects the notion of a genetically based inherent dignity to a human right of individuals to be free of genetic manipulation. With regard to the “dignity of the human being,” the preamble speaks of the “need to respect the human being both as an individual and as a member of the human species. ” The 1976 on Economic, Social and cites this sentence in its preamble and then states that “these rights derive from the inherent dignity of the human person. [SEP] Justify:

Output: The text contrasts the claim by suggesting that genetic engineering, particularly human germline genetic engineering, poses potential risks not only to individuals but to the species itself. It discusses the need for responsible manipulation of the human genome and highlights the inherent risks associated with genetic engineering, thereby questioning the notion of extending human life indefinitely without health risks.


Input: Task: pass the claim using the given text. Claim: Action potentials are generated by the movement of sodium and potassium ions across the neuron membrane. [SEP] Text: (F) Top, population data showing significant decreases in mean Vm and EGABA but not DF five minutes after electroporation. Below: changes in DF over time. Point at which electroporation occurred marked with orange arrow. ‘ns’, non-significant; *p<0. 05. The data for ‘D’, ‘E’ and ‘F’ is provided in Figure 5—source data 1. Figure 5—source data 1 Source data for Figure 5D–F. Resting membrane potential, EGABA and driving force at time points as indicated relative to electroporation of anionic dextran (at time 0 min), for each experiment. Download elife-39575-fig5-data1-v3. xlsx Figure 5—figure supplement 1 Download asset Open asset Large volume shifts occur when average impermeant charge is changed via temporary anion species flux across the membrane. Repeating the methodology in Figure 5C for ion species with different charges (zflux) demonstrates the effect of driving shifts in the average intracellular impermeant charge on cell volume. Generating even small shifts in average z by adding or removing impermeant anions can cause large changes in cell volume. Figure 6 with 1 supplement Download asset Open asset Impermeant anions drive small shifts in chloride driving force by modifying the Na+/K+-ATPase pump rate under conditions of active chloride cotransport. (A) ECl (green), EK (purple) and Vm (black) (top panel), [Na+]i (pink, middle panel) and mean impermeant anion charge z (orange, lower panel) over time in the default single compartment model. Changing z from −0. 85 to −1 generated small, persistent Cl- driving force (DF) shifts (arrows, red) only when the effective ATPase pump rate (Jp) was variable (solid line) and not when Jp was kept constant (dashed line). (B) Solving analytically across different values of z with either a variable Jp (solid lines) or a constant Jp (dashed line), demonstrates the direct relationship between Na+ (pink), effective pump rate (Jp) (top panel) and DF (lower panel, red). [SEP] Justify:

Output: The text does not directly address the claim regarding action potentials and the movement of sodium and potassium ions. While it discusses ion flux and driving forces, it does not confirm or contradict the specific claim about how action potentials are generated, thus making it irrelevant.


Input: Task: corroborate the claim using the given text. Claim: Small businesses are crucial to local economies and job creation. [SEP] Text: This leads to the second stage where there is increased factor productivity due to the innate desire for increased production which leads to higher efficiency and higher economies of scale, scope and size. Following this, the third stage is the increased rate of employment involving the utilisation of idle and underutilised productive resources including labour. The outcome is the higher income per capita stage. Per capita income increases as a result of higher demand for factor inputs and increased relative scarcity of productive resources. Next comes higher consumption per capita stage as increased access to employment reduces financial dependency rates and income earners effectively demand necessities of life. These necessities include quality food, healthcare, shelter and protection, education and training, clothing, and security. In the sixth and final stage, there is a manifestation of poverty reduction to the extent that the vicious cycle is broken, and households escape from the low-income trap through entrepreneurship. It is important to stress that relying solely on one business or income stream can be risky in most developing countries. Hence, there is a need for poverty-escapee households to diversify their sources of income by exploring multiple entrepreneurial ventures, investments, or other income-generating activities. Other strategies to protect households from slipping into the low-level equilibrium trap include the establishment of emergency funds or enrolling social insurance schemes, prudent investment, continuous learning, and personal development. Even though, in general, the availability and easy access to any of the essential determinants of entrepreneurship through a policy intervention is the beginning of breaking the poverty cycle, in low-income countries, financial constraints—lack of adequate equity capital and high cost of borrowing arising from excess demand for investible funds—are probably the most prominent barrier for growth and development of entrepreneurship. It is, thus, believed that holding all other factors constant, a policy intervention by way of making investible funds available to potential entrepreneurs would go a long way in creating job opportunities, raising incomes, and reducing the high incidence of poverty in low-income economies. 5. 2. Evidence-of the 5. 2. 1. Entrepreneurship, Income, Employment, and Poverty in Figure 6 provides some empirical evidence that there is a trend relationship between entrepreneurship as proxied by business density rate, income and poverty reduction in developing economies between 2014 and 2020. As entrepreneurship (business density rate) increases from 17. 53 percent in 2014 to 27. 03 percent in 2020, real annual per capita income increases5 steadily from US$2489. [SEP] Justify:

Output: The text corroborates the claim by highlighting the positive relationship between entrepreneurship and economic outcomes, such as job creation and income increase. It discusses how the increase in business density leads to higher per capita income and employment opportunities, thus supporting the assertion that small businesses play a critical role in local economies and job creation.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering can extend human life indefinitely without health risks. [SEP] Text: ” (Beyond those I discuss, other instruments that posit an inherent human dignity include the 1976 of Civil and Political Rights, the 1981 Convention on the Elimination of of Women, the 1987 Torture and Other Cruel, Inhumane, or Punishment, and the 1989 Convention on the Rights of the Child. ) By means of the essentializing notion of inherent qualities—permanent and inseparable attributes, in other words, an essence—it seeks to defend human dignity by prohibiting genetic editing. (Convention thereby confuses changing an individual’s genome with changing the germline. ) Beriain (Reference de Miguel Beriain2018) invites us to imagine a “human embryo with mutations of the Huntington gene that will inevitably lead to Huntington’s disease if the embryo grows into a human being. If we edit its germline to replace the gene with a normal variant, we will modify the embryo’s genome but not the human genome. The ultimate result of the intervention—a human being with a genome that does not show the specific pathological variant that triggers Huntington’s disease—will not introduce any novelty into the human gene pool” (p. 3). (Reference Andorno2013) is vulnerable at this point to the genetic essentialism of deriving human rights from a notion of human dignity understood as a trait inherent to human beings: “each human being, as a holder of intrinsic dignity, is entitled to inalienable rights, which are the same for all, regardless of their genetic make-up” (p. 90). To remain consistent with the rest of his reading of the on the he would better view the notion of human dignity symbolically, as a social construct that, as a political tool, can be deployed in the cultural project of advocating equal legal rights for all persons. 4. Alternative to genetic essentialism: dignity as a future person’s decisional autonomy In place of framing human identity as the human genome (a biological identity), I frame it as human dignity: a socially constructed, political identity. I assign a political and legal status to the human genome and then derive, from that status, a human right to dignity. (I also reject the idea that human rights somehow derive from our species’ genetic identity; I view them as social constructs [see Gregg, Reference Gregg2012, Reference Gregg2016, Reference Gregg2021]. ) I begin by analyzing dignity. [SEP] Justify:

Output: The text contrasts the claim by discussing the implications of genetic editing and the inherent human dignity associated with human rights rather than supporting the notion that genetic engineering can extend human life indefinitely without health risks. It delves into the complexities of genetic editing, human dignity, and rights, suggesting that modifications to the human genome do not change the genetic identity of humanity as a whole, and raises ethical concerns around the use of genetic engineering.


Input: Task: pass the claim using the given text. Claim: Action potentials are generated by the movement of sodium and potassium ions across the neuron membrane. [SEP] Text: ECl (green), EK (purple) and Vm (black) (top panel), [Na+]i (pink, middle panel) and average impermeant anion charge z (orange, lower panel) over time in the default single compartment model. Changing the average z from −0. 85 to −1 generated small, persistent Cl- driving force shifts (arrows) only when the effective ATPase pump rate (Jp) was variable (solid and dashed line) for both pump models, and not when Jp was kept constant (dotted line). (B) The experiment for Figure 6C was repeated comparing the usual ATPase model (solid line) with Hamada et al. , 2003’s model and is consistent with the results in the main text. ECl (green), EK (purple) and Vm (black) (top panel), [Na+]i (pink, middle panel) and cell volume (black, lower panel) over time in the default single-compartment model. Impermeant anions of the same average charge of the cell were added. A volume constraint on Hamada et al. ’s model was incorporated by adding a hydrostatic force dependent on membrane tension (dotted lines), which resulted in an impermeable anion induced transmembrane osmotic differential. This caused a small change in Cl- driving force when Jp was variable (dotted line), but not when Jp was held constant (dash-dotted lines). Figure 7 Download asset Open asset Local changes in KCC2 activity generate local differences in chloride reversal and driving force only under conditions of constrained chloride diffusion. (A) Schematic depicting the multi-compartment model representing a virtual dendrite of length 100 μm. The virtual dendrite consists of 10 compartments of length 10 μm and initial radius 0. 5 μm. Each compartment contains the same mechanisms and default parameterization as the single compartment model. All ions, except impermeant anions, could move between compartments by electrodiffusion. (B) Top panel, ECl (green), EK (purple), Vm (black) and DF (arrows, red) from the second from top compartment (indicated with a white triangle) where the conductance of KCC2 was increased. [SEP] Justify:

Output: The text does not directly address the claim regarding the generation of action potentials and the specific role of sodium and potassium ions in this process. It discusses various parameters and models related to ion movements and membrane dynamics, but does not explicitly confirm or deny the specific mechanism through which action potentials are generated.


Input: Task: corroborate the claim using the given text. Claim: Small businesses are crucial to local economies and job creation. [SEP] Text: In this regard, a collaborative effort from the central government, local government, non-governmental organisations including native associations resident locally or abroad, and religious bodies should be critical in this regard; · labour wages and national compensation policies must be designed and enforced to ensure that, in real terms, minimum wages are above the statutory unemployment compensation rates; · regulatory reforms, privatisation, civil service reforms, trade liberalisation and economic openness, financial sector reforms, and improved governance could be key structural measures that governments may pursue to support economic growth and development; and, · coordinating efforts at the international, national, and local levels to support entrepreneurship development to propel accelerated growth and sustainable development. NOTES *Originally an unpublished09/001 presented by the author at the Inaugural/Programme of the of Economists of on August 15, 2009. 1Jobs are created directly and indirectly through the chain of interrelated value-addition processes within and outside the enterprise. It is common to find positive spillover effects concerning job creation. 2A survey by Dun and Bradstreet Holdings, Inc. (2002) on small-scale business owners shows that 17% strictly devoted at least 60 hours a week to their businesses. Again, about 50% of these entrepreneurs spend between 41 and 60 hours a week on their businesses. 3Based on 150 countries/regions viz. and (China), of (China), and Tobago, Tunisia, Türkiye, and Zimbabwe. The selection was strictly based on the availability of consistent data. 4Persons trapped in the vicious cycle of poverty. 5The sharp decline in per capita income in the year 2020 could be attributed to the effects of COVID-19. 6Econometrically, these results cannot be reliable as test is not applicable to cross-sectional inclined data as is the case for the panel dataset with an N > T structure. 730 LDCs covered are ôte d’and Zambia. The selection was based purely on the availability of consistent data. Conflicts of author declares no conflicts of interest regarding the publication of this paper. 226. [2] Coleman, B. E. (2006). Microfinance in Northeast Thailand: World Development, 34, 1612-1638. [3] Dun and Bradstreet Holdings, Inc. (2002). 21st. Washington D. C. [4] Hulme, D. (1999). [SEP] Justify:

Output: The text corroborates the claim by discussing how jobs are created directly and indirectly through the value-addition processes surrounding small businesses. It highlights the positive spillover effects related to job creation and provides statistics showing the commitment of small business owners, suggesting their significant role in fostering local economies and creating jobs. This aligns with the claim that emphasizes the importance of small businesses in local economies.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering can extend human life indefinitely without health risks. [SEP] Text: The international instruments I reviewed earlier wield the term “human dignity” in ways that are indeterminate in meaning. Indeterminacy hardly impedes the authors’ intention: to legitimize a viewpoint. Their intention is familiar from older debates about a right to physician-assisted suicide, a right to privacy, or a right against self-incrimination, where such debates invoke a legitimizing notion of human dignity. Current debates also draw on human dignity to reject human genetic engineering (e. g. , to support a future person’s putative right not to be genetically modified). The term “human dignity” has no rational grounds as long as it remains indeterminate in meaning, and as long as it treats — as intuitively evident or as a first principle of a metaphysical or theological vision about human good — a putative right not to be genetically modified. To render the term rationally useful, its legitimizing function must be grounded in a determinate meaning. Any particular definition follows from the definer’s cognitive interest in defining. Mine is informed by consequentialism, a philosophical position that, while not itself scientific, does not contradict any claims of natural science or a naturalistic understanding of the human being. Consequentialism holds that whether an act is morally right depends only on it consequences, or that those actions are right that render the future world the best possible world. In a consequentialist spirit, I define “dignity” as the individual’s decisional autonomy vis-à-vis other persons— such as the autonomy afforded by the right to choose whether and how to be genetically engineered. Autonomy is choice, and choice is the “recognizable capacity to assert claims,” whereby a person is understood as a “potential maker of claims” (Feinberg, Reference Feinberg1970, 5. A future person’s interest in decisional autonomy When speaking of present persons, I speak of those persons in a position to decide whether and how to genetically modify an embryo that will develop into a future person. On a broad understanding of justice such as Mill’s (Reference Mill2001, ch. 5), might present persons have a duty of justice toward future persons? Might future persons have rights vis-à-vis present persons? [SEP] Justify:

Output: The text contrasts the claim by discussing the ethical implications and debates surrounding human genetic engineering. It highlights the opposition to genetic modification based on the concept of 'human dignity' and suggests that there are substantial moral concerns about the right not to be genetically modified. The mention of a 'putative right not to be genetically modified' implies skepticism toward the notion that genetic engineering can be pursued without health risks or ethical dilemmas, thereby challenging the claim that it can extend human life indefinitely without risk.


Input: Task: pass the claim using the given text. Claim: Action potentials are generated by the movement of sodium and potassium ions across the neuron membrane. [SEP] Text: The insets depict the diameter, and absolute change from baseline of ECl, Vm and DF for all compartments before (i), during (ii) and after (iii) the activity of KCC2 was selectively increased. This resulted in ECl decreasing in all compartments with minimal changes to EK and V. Consequently, the Cl- DF (red) increased. In this case the diffusion constant for Cl- (DCl = 2. 03×10−7 dm2. s−1) resulted in ECl and DF changes being widespread across the virtual dendrite. (C) Reducing the Cl- diffusion constant to 0. 2 × 10−7 dm2. s−1 resulted in a localized effect of compartment-specific KCC2 activity increases on ECl and DF. Figure 8 Download asset Open asset Local changes in impermeant anions do not establish the local driving force for chloride. (A) Multi-compartment model of a 10 compartment 100 μm virtual dendrite as in Figure 7. (B) Top panel, ECl (green), EK (purple), Vm (black) and DF (arrows, red) within the compartment where additional impermeant anions were exclusively added (indicated with a white triangle). The insets depict the diameter, and absolute change from baseline for ECl, Vm and DF for each compartment of the virtual dendrite before (i), during (ii) and after (iii) impermeant anions were added. The selective addition of impermeant anions of default charge (z = −0. 85) to the 2nd from top compartment resulted in transient but non-permanent shifts in ECl, Vm and the Cl- DF in all compartments. The volume of the compartment where impermeant anion addition occurred increased permanently. (C) Traces and insets as in ‘B’ showing the addition of impermeant anions of more negative charge in order to decrease z in the second from top compartment specifically. Note that during addition of impermeant anions, ECl, EK, Vm changed. We also observed persistent decreases in ECl and Vm in the compartment manipulated, with a negligible change in DF (0. 01 mV). Again, impermeant anion addition resulted in an increase in the volume of the specific dendritic compartment manipulated. [SEP] Justify:

Output: The text is irrelevant to the claim as it focuses on the effects of chloride dynamics and impermeant anions in a multi-compartment model of a virtual dendrite. It does not discuss the generation of action potentials or the roles of sodium and potassium ions in this process.


Input: Task: pass the claim using the given text. Claim: All high-paying jobs require a college degree. [SEP] Text: In the second stage of our analysis, we used a meta-analytic approach to summarize findings across institutions (Cooper & Hedges, 1994; Lipsey & Wilson, 2001). Although the impact studies for each institution followed a generally consistent approach, there was some variation among the OER initiatives and the institutions rolling them out as described (see the “Research context and procedure” section). Using meta-analysis offered more flexibility to combine the results across individual studies with variation as compared to combining the data into a single analysis. Though it was not possible to test for interactions between student- and institutional-level characteristics, our meta-analytic approach allowed us to explore implementation and study design features that are associated with the size of the impact in different institutions. ResultsDescriptive statisticsTable 3 presents the characteristics of the final analysis samples for each site in terms of size and student demographics. These data are for the matched samples, after propensity score matching was used to establish baseline equivalence between the treatment and comparison conditions. The sample size available for analysis ranged considerably across the 11 colleges, with some having samples in the low hundreds and others approaching 5,000. With the exception of one site, the average student age was around 20 years old. At least a third or more of the sample at each college consisted of students eligible for or who had received Pell grants. The proportion of students from historically underrepresented ethnic minority groups ranged considerably across colleges from 25 to 88%. Table 3 Demographic characteristics of the final analysis samples, by collegeFull size tableRQ1 main impact analysisCredit accumulationIn 6 of the 11 colleges, treatment students taking OER courses accumulated significantly more course credits than those who had not taken any OER courses (see Table 4). The number of additional credits accumulated by treatment students ranged from 2 to 8 across these six schools. In the remaining 5 colleges, students’ credit accumulation in the two conditions was not statistically different after controlling for differences in student characteristics. Table 4 Credit accumulation results, by collegeFull size tableTable 4 also shows the estimated effect size for each of the research partner colleges on credit accumulation. An effect size is a standardized measure of the magnitude of an effect and is calculated as the standardized mean difference between two groups. The effect size increases in magnitude as the difference between the groups on the outcome measure gets larger. The U. S. Department of Education’s Clearinghouse (2017) defines effect sizes equal or greater than 0. [SEP] Justify:

Output: The text does not address the claim regarding high-paying jobs and their educational requirements. It discusses a meta-analytic approach to summarize findings across institutions about credit accumulation and demographic characteristics of student samples. There is no information in the text that corroborates or contrasts with the claim.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering can extend human life indefinitely without health risks. [SEP] Text: Log in or new issue alertsGet alerts Enter your Email address: Subscribe to e2010. | DOI: 10. 1097/01. COT. 0000387939. 55124. 80 —Clinicians can extend the lives of patients whose solid tumors are refractory to standard therapies by looking deep into the tumor’s genome in search of its Achille’s heel. Matching a mutation that defines the tumor’s vulnerability with a specific agent is particularly important for patients in the last 12 weeks of life. So said Daniel D. Von Hoff, MD, Physician in Chief and at the in Phoenix, presenting the 2010 David A. here at the which he titled, “12 Weeks. ” “trials can be more therapeutic for the individual patient sitting in front of us right now. Do whatever it takes to maximize a patient’s chances of having a benefit from a specific agent. Let’s not just try the next new agent to come along. ” Over the last 35 years, Dr. has taken 317 new anticancer agents into clinical trials with four different clinical trial teams. I trials include patients who have not responded to multiple standard therapies, and have a life expectancy of 12 weeks, a Karnofsky status of at least 70%, and acceptable hepatic and renal function. “People trust us in this time of their life for the best help we can possibly provide with a great sense of urgency,” Dr. said. “[A trial] may be the last thing our patients have an opportunity to try. ” three of the first 26 (8%) new agents he took into trials had evidence of clinical antitumor activity. To improve a patient’s chance of response, he began to utilize the human tumor cloning assay (HTCA). “There are quite a few drugs we now use every day because a specific patient went on a specific agent suggested by the HTCA. When using the HTCA to select patients, we saw responses, dramatic responses, durable responses, in almost every trial. ” The agents first identified in this way include docetaxel, temsirolimus, irinotecan, and gefitinib. [SEP] Justify:

Output: The text contrasts the claim by discussing the challenges and limitations in extending human life, specifically in the context of cancer treatment. It highlights that while genetic and genomic strategies may improve treatment prospects, they are focused on extending life in critically ill patients and are not guaranteed to be free from health risks, as it mentions the urgency and complex decisions involved in treating patients with serious conditions.


Input: Task: pass the claim using the given text. Claim: Action potentials are generated by the movement of sodium and potassium ions across the neuron membrane. [SEP] Text: 1 Constants, default parameters and usual steady state values for variables used in the biophysical models. ValueDescriptionConstantsF96485. 33 C/molFaraday constantR8. 31446 J/(K. mol)Universal gas constantT310. 15 KAbsolute temperature (=37°C)ParametersCm2× 10−6 F/cm2Unit membrane capacitance (Qian and Sejnowski, 1989)gNa20 µS/cm2Na+ leak conductance (Kager et al. , 2000)gK70 µS/cm2K+ leak conductance (Kager et al. , 2000)gCl20 µS/cm2Cl- leak conductancegKCC220 µS/cm2KCC2 conductance (Doyon et al. , 2016)vw0. 018 dm3/molPartial molar volume of water (Hernández and Cristina, 1998)pw0. 0015 dm/sOsmotic permeability (Hernández and Cristina, 1998)km25 N/dmVariable for membrane tension (higher than reported (Dai et al. , 1998): used in this paper to accentuate differences in osmolarity)p0. 1 C/(dm2. s)Default pump rate constant[Na+]o145 mMExtracellular Na+ concentration[K+]o3. 5 mMExtracellular K+ concentration[Cl-]o119 mMExtracellular Cl- concentration[X-]o29. 5 mMExtracellular impermeant anion (X) concentration (Lodish et al. , 2009; Raimondo et al. , 2015)DNa1. 33 × 10−7 dm2/sNa+ diffusion constant (Hille, 2001)DK1. 96 × 10−7 dm2/sK+ diffusion constant (Hille, 2001)DCl2. 03 × 10−7 dm2/sCl- diffusion constant (Hille, 2001)Variables (default steady state)Vm−72. 6 mVMembrane potential[Na+]i14. 0 mMIntracellular Na+ concentration[K+]i122. 9 mMIntracellular K+ concentration[Cl-]i5. [SEP] Justify:

Output: The text is largely comprised of constants, parameters, and values regarding the biophysical models of neuron membranes, including concentrations and conductances of sodium (Na+), potassium (K+), and chloride (Cl-) ions, as well as various diffusion constants. However, it does not directly address or support the claim about the generation of action potentials through ion movement. Therefore, it is considered irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Climate change has contributed to more frequent and intense heatwaves. [SEP] Text: 1 IntroductionSummer heatwaves have received intensive attention over the past decades due to their severe adverse impacts on human society and ecosystems. summer heatwave in 2003 was responsible for more than 35,000 deaths and economic losses of 10 billion USD (Fischer et al. 2007). This event also led to forest fires in Portugal and associated severe damages to ecosystems with economic losses of more than 1 billion Euros (García-Herrera et al 2010). The USA summer heatwave in 1988 resulted in 5000–10,000 deaths (2001). An estimated 840 deaths of Canada and the USA resulted by the direct consequences of the America heatwave in 2021 (Overland 2021). Heatwaves also have negative effects on crops, livestock, and milk production (Sejian et al. 2012). Meanwhile, the frequency of heatwaves has increased in large parts of Europe and Asia since the middle of the twentieth century (Seneviratne et al. 2021). Peterson et al. (2013) reported the highest and second highest number of heatwaves occurred in the 1930s and 2000s decades in the USA; however, a higher number of heatwaves in the 2010s than in the 2000s were reported (Alizadeh et al. 2022). Anthropogenic global warming is blamed for increased probability of heatwave occurrences (e. g. , Fischer and Knutti 2015; Seneviratne et al. 2021). Moreover, projections from multi-model ensembles of global climate models (GCMs) suggest that heatwaves will be more intense, more frequent, and last longer over most land areas in future warming climates (e. g. , Fischer and Knutti 2015; Dosio et al. 2018). Therefore, it is important to understand the mechanisms driving heat extremes and how these mechanisms and extremes will be affected by climate change. Heatwaves occurring in mid- to high-latitudes are often associated with atmospheric blocking events, which are originally defined as quasi-stationary anti-cyclonic circulation anomalies that interrupt the predominant westerly flow and persist for several days (Trigo et al. 2004), but they are also associated with persistent or unusual features in storm tracks (Zappa et al. 2014). [SEP] Justify:

Output: The text corroborates the claim by providing evidence that anthropogenic global warming is linked to the increased probability of heatwave occurrences. It states that the frequency of heatwaves has increased since the mid-20th century and that projections from climate models suggest heatwaves will become more intense and frequent in future warming climates. Thus, the text supports the claim that climate change has contributed to the frequency and intensity of heatwaves.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering can extend human life indefinitely without health risks. [SEP] Text: Dr. provided a dramatic example of a 43-year-old man with abdominal mesothelioma whose disease had progressed on a handful of agents and who had been referred to Dr. in 1998. “We tested this patient’s tumor in the HTCA and found it to be resistant to many agents, but it was sensitive to the new anticancer agent LY2313514. We had been looking at this agent in the cloning assay to see where we might take it and what patients to put on trial,” he said. The investigational agent was active in 2 of 3 mesothelioma patients tested as well as in 9 of 36 non-small cell lung cancer (NSCLC) patients. The referred patient was sensitive to LY2313514, which is now known as pemetrexed, and the man had more than a four-year response to the drug. “This was the first patient we tested with the continual reassessment method of one patient per dose level,” he said. Pemetrexed in combination with cisplatin has since proven to extend survival of mesothelioma patients beyond 12 months. Pemetrexed is also approved for non-small-cell lung cancer and for maintenance of non-squamous histology patients. “Where you see an initial response in a trial can be critically important to the development of the agent,” noted Dr. Von Hoff. “There is a good correlation between the first response in a trial and what the new agent is initially approved for. ”. : “What do you do when in spite of all the guile and profiling you can muster against a patient’s tumor, we have nothing we think will help? But actually we do have something that helps, and that is trying to help. ”The cloning assay helped provide responses for patients in other trials and paid off in multiple areas of early drug development, including gemcitabine, irinotecan, topotecan, docetaxel, mitoxantrone, and gefitinib, among others. Then funding for the cloning assays dried up. “Unfortunately, with less direct guidance on what new agent to use, the number of responses seen in our trials dropped off dramatically. It was obvious we needed new tools to measure sensitivity or targets in a greater percentage of patients,” Dr. said. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexities involved in drug development and treatment responses for cancer patients, which implies that while there are advancements in medical treatments, extending human life indefinitely without health risks is not presented as a feasible outcome. Specifically, it highlights that the investigational agent pemetrexed has shown effectiveness in certain cancer cases, but it does not suggest that this is a solution for indefinite human life extension or that it comes without health risks.


Input: Task: pass the claim using the given text. Claim: Action potentials are generated by the movement of sodium and potassium ions across the neuron membrane. [SEP] Text: Skip to Content eLife home page your research Search by keyword or author Reset form my search to 10. 7554/eLife. 13378 Open access Copyright information Version of RecordApril 26, 2016 Accepted ManuscriptMarch 29, 2016 Accepted ManuscriptMarch 23, 2016 Open annotations (there are currently 0 annotations on this page). 6,717 views 1,545 downloads 110 3378. Copy to clipboard Download BibTeX Download. RIS Full text Figures and data Peer review Side by side Figures 6 figures 1 with 2 supplements Download asset Open asset Rapamycin treatment increased neuronal ATP levels. (A) The effect of rapamycin (RAPA) on cellular ATP level was examined in 5-week neurons differentiated from human neuroprogenitor cells (NPCs) derived from H9 ESCs. Rapamycin was used at 20 nM (final concentration). Mitochondrial dysfunction was mimicked by chemicals disrupting mitochondrial oxidative function: oligomycin (2 µM), blocking complex V (ATP synthase); rotenone and antimycin A (R&A; 1 µM each), complex I and III inhibitors; CCCP (20 µM), a mitochondrial uncoupler. All were prepared in DMSO as vehicle. N-acetylcysteine (NAC) was used at 750 µM (final concentration). The treatment was done for 6 hr with neurons grown in duplicate wells from the same batch of differentiation. The relative ATP level for each treatment was calculated as percentage after normalization to DMSO-treated neurons. Bars are mean ± SD, n=3. *p<0. 05. **p<0. 01, calculated by two-tailed t-test. (B) Immunoblot analysis of cell lysates prepared from neurons treated with oligomycin, rapamycin or both for 6 hr. The intensity of phosphorylated protein was quantified after normalization to non-phosphorylated signal, and was presented as fold change compared to control group treated with DMSO. (C) Immunoblot analysis of cell lysates prepared from neurons treated with oligomycin or AICAR for 6 hr. (D) Oxygen consumption rate (OCR) measurement by Seahorse extracellular flux analyzer. The basal OCRs of neurons treated with rapamycin for 6 hr were compared to neurons treated with DMSO as control. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the effects of rapamycin on neuronal ATP levels and various treatments on neurons, without mentioning action potentials or the role of sodium and potassium ions in neuronal activity.