Long ago, I set out to solve a problem, but something happened along the way: I was diverted by an unexpected observation. Thereafter, the direction of my research was guided at each stage by increasing familiarity with the experimental material and what could be done with it. The result was the birth of therapy with cultured keratinocytes. Subsequent developments soon led to the formation of the company Biosurface Technology (later taken over by the Genzyme Corporation), which provided autologous cultures for (...) burn victims in many parts of the world. Further progress by others led to new therapeutic applications of cultured keratinocytes, such as treatment of an ocular disease and gene therapy. Unfortunately, there have developed serious regulatory problems that are a danger to future progress. As described in this brief history, the initial stages of development of cell therapy for the treatment of human disease were possible only because there was no restraint by committees or governmental regulations. BioEssays 30:897–903, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

In this article I rebut conservative objections to five phases of embryonic stem cell research. I argue that researchers using existing embryonic stem cell lines are not complicit in the past destruction of embryos because beneficiaries of immoral acts are not necessary morally tainted. Second, such researchers do not encourage the destruction of additional embryos because fertility clinics presently destroy more spare embryos than researchers need. Third, actually harvesting stem cells from slated-to-be-discarded embryos is not wrong. The embryos (...) are not sacrificed for the good of others because they would have been destroyed anyway. Fourth, harvesting stem cells from embryos that are not doomed is morally acceptable, because preserving frozen embryos is futile therapy. Finally, creating embryos solely for the sake of harvesting stem cells from them is morally acceptable because the assumption that embryos have the right to life has very counterintuitive implications. (shrink)

Howard W. Jones, Jr.'s Personhood Revisited chronicles reproductive technology's debate-evoking history meanwhile exploring the ongoing moral dilemmas of the twenty-first century, including: personhood, in vitro fertilization, conjugal love, eugenics, cloning, stem cell research, and more. Balanced readings on each reproductive topic represent conflicting viewpoints from legal, religious, and scientific perspectives. And Jones' personal experiences, such as meetings with the Vatican, add a unique look into the highly political yet benevolent world of reproductive medicine. Author Howard W. Jones, (...) Jr., alongside Robert Edwards (winner of the Nobel Prize for Medicine 2010), fertilized the first human eggs in vitro. Jones and his wife, Georgeanna Seegar Jones, established the first in vitro fertilization program in the United States, which went on to develop America's first test tube baby in 1981. Book jacket. (shrink)

Tissues are shaped and patterned by mechanical and chemical processes. A key mechanical process is the positioning of the mitotic spindle, which determines the size and location of the daughter cells within the tissue. Recent force and position-fluctuation measurements indicate that pushing forces, mediated by the polymerization of astral microtubules against­ the cell cortex, maintain the mitotic spindle at the cell center in Caenorhabditis elegans embryos. The magnitude of the centering forces suggests that the physical limit on the (...) accuracy and precision of this centering mechanism is determined by the number of pushing microtubules rather than by thermally driven fluctuations. In cells that divide asymmetrically, anti-centering, pulling forces generated by cortically located dyneins, in conjunction with microtubule depolymerization, oppose the pushing forces to drive spindle displacements away from the center. Thus, a balance of centering pushing forces and anti-centering pulling forces localize the mitotic spindles within dividing C. elegans cells. We discuss microtubule-based mechanisms of the mitotic spindle positioning, a key mechanical process that shapes and patterns tissues. The magnitude of the centering forces indicates that the physical limit on the accuracy and precision of centering is set by the number of contributing microtubules rather than by thermally driven fluctuations. (shrink)

This book attempts to marry truth-conditional semantics with cognitive linguistics in the church of computational neuroscience. To this end, it examines the truth-conditional meanings of coordinators, quantifiers, and collective predicates as neurophysiological phenomena that are amenable to a neurocomputational analysis. Drawing inspiration from work on visual processing, and especially the simple/complex cell distinction in early vision (V1), we claim that a similar two-layer architecture is sufficient to learn the truth-conditional meanings of the logical coordinators and logical quantifiers. As a (...) prerequisite, much discussion is given over to what a neurologically plausible representation of the meanings of these items would look like. We eventually settle on a representation in terms of correlation, so that, for instance, the semantic input to the universal operators (e.g. and, all)is represented as maximally correlated, while the semantic input to the universal negative operators (e.g. nor, no)is represented as maximally anticorrelated. On the basis this representation, the hypothesis can be offered that the function of the logical operators is to extract an invariant feature from natural situations, that of degree of correlation between parts of the situation. This result sets up an elegant formal analogy to recent models of visual processing, which argue that the function of early vision is to reduce the redundancy inherent in natural images. Computational simulations are designed in which the logical operators are learned by associating their phonological form with some degree of correlation in the inputs, so that the overall function of the system is as a simple kind of pattern recognition. Several learning rules are assayed, especially those of the Hebbian sort, which are the ones with the most neurological support. Learning vector quantization (LVQ) is shown to be a perspicuous and efficient means of learning the patterns that are of interest. We draw a formal parallelism between the initial, competitive layer of LVQ and the simple cell layer in V1, and between the final, linear layer of LVQ and the complex cell layer in V1, in that the initial layers are both selective, while the final layers both generalize. It is also shown how the representations argued for can be used to draw the traditionally-recognized inferences arising from coordination and quantification, and why the inference of subalternacy breaks down for collective predicates. Finally, the analogies between early vision and the logical operators allow us to advance the claim of cognitive linguistics that language is not processed by proprietary algorithms, but rather by algorithms that are general to the entire brain. Thus in the debate between objectivist and experiential metaphysics, this book falls squarely into the camp of the latter. Yet it does so by means of a rigorous formal, mathematical, and neurological exposition – in contradiction of the experiential claim that formal analysis has no place in the understanding of cognition. To make our own counter-claim as explicit as possible, we present a sketch of the LVQ structure in terms of mereotopology, in which the initial layer of the network performs topological operations, while the final layer performs mereological operations. The book is meant to be self-contained, in the sense that it does not assume any prior knowledge of any of the many areas that are touched upon. It therefore contains mini-summaries of biological visual processing, especially the retinocortical and ventral /what?/ parvocellular pathways computational models of neural signaling, and in particular the reduction of the Hodgkin-Huxley equations to the connectionist and integrate-and-fire neurons Hebbian learning rules and the elaboration of learning vector quantization the linguistic pathway in the left hemisphere memory and the hippocampus truth-conditional vs. image-schematic semantics objectivist vs. experiential metaphysics and mereotopology. All of the simulations are implemented in MATLAB, and the code is available from the book’s website. • The discovery of several algorithmic similarities between visison and semantics. • The support of all of this by means of simulations, and the packaging of all of this in a coherent theoretical framework. (shrink)

Single‐stranded DNA‐protein complex (T‐complex) is proposed to mediate T‐DNA transfer from Agrobacterium to plant cells. A novel model for transfer is presented which incorporates features of both bacterial conjugation and viral infection. Specific protein components of the T‐complex, its ultrastructure and possible functions in the plant cell are discussed.

Barry Commoner has argued that the environmental failure of modern technology is due in large part to the reductionistic character ofmodern science, especially its biological component where the reductionist approach has triumphed in molecular biology. I claim, first, that Commoner has confused reduction in the sense of the reduction of one theory to another with what is better called analysis, or the strategy of breaking a whoie into its parts in order to understand the properties of the whole, this latter (...) being the actual target of his attack. I then argue that his criticisms of molecular biology fail since each of the properties of the cell which he claims cannot be understood in an analytic fashion, such as reproduction, development and inheritance, can be so understood, and that, in fact, each of his putatively nonanalytic accounts of these properties is the result of analysis. Similarly, Commoner’s claim that ecosystenls possess properties that cannot be understood analytically is refuted by comparing ecosystems with automobiles, which Commoner acknowledges are susceptible to analysis, and by showing that there are no essential differences between the two. FinaIly, l observe that while it is false that ecosystems canna! be understood in analytic terms, it is true that they are not usually thus understood, and that the explanation for this is not that scientists subscribe to amistaken philosophy, but that our social institutions for the teaching and application of science do not adequately stress the importance of exploring the connections between the parts of such complex wholes. (shrink)

In Unbiased Stereology, the authors present a practical guide to making unbiased 3D measurements using microscopy. Stereology is the statistical inference of geometric parameters from spatially sampled information; it is considered unbiased when the test probes are positioned in an appropriately random manner. Now that unbiased stereology is required for nerve-cell counts in neurotoxicology by the FDA and by many journals before the acceptance of an article or study, this book is essential reading. It includes only those stereological techniques (...) that have been tried and tested by actual application. Specific topics covered include: random sampling and random geometry; the estimation of feature volume, surface, length, number and mean particle size; as well as statistics for stereologists. (shrink)

Gap junctions are ubiquitous plasma membrane specializations that allow cells to exchange small molecules and ions directly. The isolation, biochemical characterization and molecular cloning of the major protein of rat liver gap junctions lead to a clearer view of these membrane zones that allow cells to ‘talk’ to each other and co‐ordinate their activities in tissues and organs.

The eukaryotic cell is partitioned by membranes into spatially and functionally discrete subcellular organelles. In addition, the cytoplasm itself is partitioned into discrete subregions that carry out specific functions. Such compartmentation can be achieved by localizing proteins and RNAs to different subcellular regions. This review will focus on localized RNAs, with a particular emphasis on RNA localization mechanisms and on the possible biological functions of localization of these RNAs. In recent years, an increasing number of localized RNAs have been (...) identified in a variety of cell types among many animal species. Emphasis here will be on localized RNAs in the most intensively studied systems – Drosophila and Xenopus eggs and early embryos. (shrink)

Background: Hematopoietic stem cell transplantation is a potential cure for a range of life-threatening diseases, but is also associated with a high mortality rate. Nurses encounter a variety of situations wherein they are faced with discussing bad news with hematopoietic stem cell transplantation patients. Research objective: The aim of this study was to explore the experiences and strategies used by Iranian nurses related to truth-telling and communicating bad news to hematopoietic stem cell transplantation patients. Research design: A (...) qualitative approach using content analysis of interview data was conducted. Participants and research context: A total of 18 nurses from the main hematopoietic stem cell transplantation center in Iran participated in semi-structured interviews. Ethical considerations: The Institutional Review Board of the Tabriz University of Medical Sciences and the Hematology-Oncology and Stem Cell Transplantation Research Center affiliated with the Tehran University of Medical Sciences approved the study. Findings: In the first main category, not talking about the disease and potential negative outcomes, the nurses described the strategies of not naming the disease, talking about the truth in indirect ways and telling gradually. In the second main category, not disclosing the sad truth, the nurses described the strategies of protecting patients from upsetting information, secrecy, denying the truth and minimizing the importance of the problem. The nurses used these strategies to minimize psychological harm, avoid patient demoralization, and improve the patient’s likelihood of a fast and full recovery. Discussion: The priority for Iranian hematopoietic stem cell transplantation nurses is to first do no harm and to help patients maintain hope. This reflects the Iranian healthcare environment wherein communicating the truth to hematopoietic stem cell transplantation patients is commonly considered inappropriate and avoided. Conclusion: Iranian nurses require education and support to engage in therapeutic, culturally appropriate communication that emphasizes effective techniques for telling the truth and breaking bad news, thereby potentially improving patient outcomes and protecting patient rights. (shrink)

Spermatogenesis is an elaborate process involving both cell division and differentiation, and cell‐cell interactions. Defects in any of these processes can result in infertility, and in some cases these can be genetic in cause. Mapping experiments have defined at least three regions of the human Y chromosome that are required for normal spermatogenesis. Two of these contain the genes encoding the RNA binding proteins RBM and DAZ, suggesting that the control of RNA metabolism is likely to be (...) an important control point for human spermatogenesis. A similar analysis in mice has shown that at least two regions of the mouse Y chromosome are essential for spermatogenesis. Both genetic and reverse genetic approaches have been used to identify mouse autosomal genes required for spermatogenesis. These studies have shown that genes in a number of different pathways are essential for normal spermatogenesis, and also provide putative models of human infertility. (shrink)

Gap junction intercellular communication channels permit the exchange of small regulatory molecules and ions between neighbouring cells and coordinate cellular activity in diverse tissue and organ systems. These channels have short half‐lives and complex assembly and degradation pathways. Much of the recent work elucidating gap junction biogenesis has featured the use of connexins (Cx), the constituent proteins of gap junctions, tagged with reporter proteins such as Green Fluorescent Protein (GFP) and has illuminated the dynamics of channel assembly in live cells (...) by high‐resolution time‐lapse microscopy. With some studies, however, there are potential short‐comings associated with the GFP chimeric protein technologies. A recent report by Gaietta et al., has highlighted the use of recombinant proteins with tetracysteine tags attached to the carboxyl terminus of Cx43, which differentially labels ‘old’ and ‘new’ connexins thus opening up new avenues for studying temporal and spatial localisation of proteins and in situ trafficking events.1 BioEssays 24:876–880, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

DNA methylation plays a role in the repression of gene expression in animal cells. In the mouse preimplantation embryo, most genes are unmethylated but a wave of de novo methylation prior to gastrulation generates a bimodal pattern characterized by unmethylated CpG island‐containing housekeeping genes and fully modified tissue‐specific genes. Demethylaton of individual genes then takes place during cell type specific differentiation, and this demodification may be a required step in the process of transcriptional activation. DNA modification is also involved (...) in the maintenance of gene repression on the inactive X chromosome in female somatic cells and the marking of parental alleles at genomically imprinted gene loci. (shrink)

In 1964 the Wisconsin virologist Howard Temin proposed the DNA provirus hypothesis to explain the mechanism by which a cancer-producing virus containing only RNA infects and transforms cells. His hypothesis reversed the flow of genetic information, as ordained by the central dogma of molecular biology. Although there was initial opposition to his hypothesis it was widely accepted, after the discovery of reverse transcriptase in 1970. Most accounts of Temin's hypothesis after the discovery portray the hypothesis as heretical, because it (...) challenged the central dogma. Temin himself in his Nobel Prize speech of 1975 narrates a similar story about its reception. But are these accounts warranted? I argue that members of the virology community opposed Temin's provirus hypothesis not simply because it was a counterexample to the central dogma, but more importantly because his experimental evidence for supporting it was inconclusive. Furthermore, I propose that these accounts of opposition to the DNA provirus hypothesis as heretical, written by Temin and others after the discovery of reverse transcriptase, played a significant role in establishing retrovirology as a specialized field. (shrink)

Cost containment by means of prospective payment and other mechanisms is widely seen as a challenge to modern medicine; but the challenge is seldom articulated clearly in terms of core professional values and the moral content of a claim to professionalism. Medical ethics, as it has evolved as a field of study in the past twenty years, has contributed little to the concept of professionalism in medicine. For an investigation of professionalism in the face of cost containment to evolve fruitfully, (...) several things must occur. The true nature of today's challenge to medicine must be appreciated. The balance between tradition and response to social change in defining a professional value system must be appreciated. Physician income must be explicitly addressed as a moral issue. And practical strategies for investigating and affirming core professional values must be developed for health delivery systems and medical education settings. (shrink)

An exploration of Immanuel Kant's account of war and the controversies that have arisen from its interpretation. This book brings the ideas of Kant's critical philosophy to bear on one of the leading political and legal questions of our age: under what circumstances, if any, is recourse to war legally and morally justifiable?

A review of the philosophical debate on theoretical models for the physician-patient relationship over the past fifteen years may point to some of the more productive questions for future research. Contractual models have been criticized for promoting a legalistic and minimalistic image of the relationship, such that another form of model (such as convenant) is required. Shifting from a contractual to a contractarian model (in keeping with Rawls' notion of an original position) provides an adequate response to many criticisms of (...) this type. A deeper criticism, however, is one that advocates a shift to a virtue-based approach. A creative amalgam between a contractarian model and elements of the virtue-based approach, combined with appropriate empirical investigation, may yield richer models in the future. (shrink)

Responding to the rash of books supporting a "new atheism" in recent years, some excellent rebuttals and refutations by Berlinski, Novak, Hart, Day, and others have also been published. The present book, however, is not a continuation of these critical salvos against the likes of Dawkins, Hitchens, Dennett, and Harris, but engages in a fresh reexamination of several important aspects of the "God-question," along with an exploration of the theory of the "faith-instinct"---a theory that emerges from a respectably long tradition, (...) but in recent years has been largely relegated to the sidelines in theology and philosophy. In the first chapter, scientific, metaphysical, and theological approaches are utilized and integrated in relationship to the question of God's existence. The second chapter is devoted to the "problem of evil," differentiated into the special categories often lumped into that all-too-generic term---moral evils, natural evils, suffering as an evil. Chapter 3 concerns the obvious follow-up question concerning what sort of characteristics, personal or otherwise, we can attribute to God---going beyond the question of God's mere "existence," even if and when we are intellectually convinced of this existence. In the second half of the book, the various meanings of "faith" are considered; and the apparent discrepancy of many New Testament descriptions of faith with the conventional Catholic and Protestant concepts of faith is investigated. Some "family resemblances" of supernatural faith seem to emerge. Then a monograph by Tubingen theologian Max Seckler, Instinkt und Glaubenswille ("Instinct and the Will to Believe"), which comments on thought-provoking texts concerning a "faith-instinct" in the works of Thomas Aquinas, is considered; Seckler brings out the philosophical and theological basis for this concept, as well as its reverberations for modern theology. The theory of a faith-instinct, however, leads to the question of the proper and improper, real or substitute, "objects," of the proposed instinct. Finally, if this instinct is, as hypothesized, implanted in human nature itself, for all places and all times, what is the function of the various religions in "activating" or placing obstacles to, the activation of this instinct? How are "false prophets," who may be instrumental in redirecting or misdirecting this instinct, to be recognized? Is faith bolstered or hindered by miracles---do miracles have any important relationship to faith? The book ends with a final consideration of the probable mental outlook of the atheist confronted with claims by theists of varying persuasions. (shrink)

This essay examines neoconservative criticisms of equity planning, and the challenges against the right of government to regulate local development and land use. The specific concern of this essay is how, or if, local development administrators (equity planners), should use their discretionary powers to ensure that city officials and private developers promote and protect the interests of urban residents, particularly the poor and disadvantaged. The essay begins by discussing the alleged conflict said to exist between needy urban residents and the (...) more secure urban taxpayers. The contrary views of equity planners are then reviewed, and the tensions within the neoconservative arguments are exposed and critiqued. Finally, the dispute between equity planners and neoconservatives is further explored by examining the dispute over the voucher system to address the problem of equal educational opportunity in urban communities. (shrink)

The nature of reference, or the relation of a word to the object to which it refers, has been perhaps the dominant concern of twentieth-century analytic philosophy. Extremely influential arguments by Gottlob Frege around the turn of the century convinced the large majority of philosophers that the meaning of a word must be distinguished from its referent, the former only providing some kind of direction for reaching the latter. In the last twenty years, this Fregean orthodoxy has been vigorously challenged (...) by those who argue that certain important kinds of words, at least, refer directly without need of an intermediate meaning or sense. The essays in this volume record how a long-term study of Frege has persuaded the author that Frege's pivotal distinction between sense and reference, and his attendant philosophical views about language and thought, are unsatisfactory. Frege's perspective, he argues, imposes a distinctive way of thinking about semantics, specifically about the centrality of cognitive significance puzzles for semantics. Freed from Frege's perspective, we will no longer find it natural to think about semantics in this way. (shrink)

The influence of Kant's philosophy has been, and continues to be, so profound and so widespread as to have become imperceptible. Philosophical inquiry within both the ‘analytic’ and the ‘continental’ traditions is unthinkable without the lexical and conceptual resources bequeathed by Kant. Even outside philosophy, in the humanities, social sciences and natural sciences, Kantian concepts and structures of argument are ubiquitous. Anyone practicing literary or social criticism is contributing to the Kantian tradition; anyone reflecting on the epistemological implications of their (...) work will find themselves doing so within parameters established by Kant. Indeed, many contemporary debates, whether in aesthetics, literary or political theory, show a peculiar tendency to mutate into disputes in Kant exegesis. All in all, in the less than 200 years since the death of its author, Kantian philosophy has established itself as an indispensable point of intellectual orientation. (shrink)

The influence of Kant's philosophy has been, and continues to be, so profound and so widespread as to have become imperceptible. Philosophical inquiry within both the ‘analytic’ and the ‘continental’ traditions is unthinkable without the lexical and conceptual resources bequeathed by Kant. Even outside philosophy, in the humanities, social sciences and natural sciences, Kantian concepts and structures of argument are ubiquitous. Anyone practicing literary or social criticism is contributing to the Kantian tradition; anyone reflecting on the epistemological implications of their (...) work will find themselves doing so within parameters established by Kant. Indeed, many contemporary debates, whether in aesthetics, literary or political theory, show a peculiar tendency to mutate into disputes in Kant exegesis. All in all, in the less than 200 years since the death of its author, Kantian philosophy has established itself as an indispensable point of intellectual orientation. (shrink)

Parallel to Koriat & Goldsmith's accounting of human memory, there are two distinct approaches in animal learning. Behaviorist approaches focus on quantitative aspects of conditioned response probability, whereas cognitive and ethological approaches focus on qualitative aspects of how memory is used in real life. Moreover, in animal research these distinguishable measures of memory are dissociated in experimental amnesia.