物质的稳定性：从原子到恒星 第四版

本书是一本关于从原子到恒星的物质稳定性专著，1991年出版第一版，由于内容新而重要，因而受到广泛的关注，这是2005年出版的第四版。     

Generation and annotation of the DNA sequences of human chromosomes 2 and 4

Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.     

Lithium isotope evidence for subduction-enriched mantle in the source of mid-ocean-ridge basalts

'Recycled' crustal materials, returned from the Earth's surface to the mantle by subduction, have long been invoked to explain compositional heterogeneity in the upper mantle. Yet increasingly, problems have been noted with this model. The debate can be definitively addressed using stable isotope ratios, which should only significantly vary in primitive, mantle-derived materials as a consequence of recycling. Here we present data showing a notable range in lithium isotope ratios in basalts from the East Pacific Rise, which correlate with traditional indices of mantle heterogeneity (for example, 143Nd/144Nd ratios). Such co-variations of stable and radiogenic isotopes in melts from a normal ridge segment provide critical evidence for the importance of recycled material in generating chemical heterogeneity in the upper mantle. Contrary to many models, however, the elevated lithium isotope ratios of the 'enriched' East Pacific Rise lavas imply that subducted ocean crust is not the agent of enrichment. Instead, we suggest that fluid-modified mantle, which is enriched during residency in a subduction zone, is mixed back into the upper mantle to cause compositional variability.     

Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis

Apoptotic cells release 'find-me' signals at the earliest stages of death to recruit phagocytes. The nucleotides ATP and UTP represent one class of find-me signals, but their mechanism of release is not known. Here, we identify the plasma membrane channel pannexin 1 (PANX1) as a mediator of find-me signal/nucleotide release from apoptotic cells. Pharmacological inhibition and siRNA-mediated knockdown of PANX1 led to decreased nucleotide release and monocyte recruitment by apoptotic cells. Conversely, PANX1 overexpression enhanced nucleotide release from apoptotic cells and phagocyte recruitment. Patch-clamp recordings showed that PANX1 was basally inactive, and that induction of PANX1 currents occurred only during apoptosis. Mechanistically, PANX1 itself was a target of effector caspases (caspases 3 and 7), and a specific caspase-cleavage site within PANX1 was essential for PANX1 function during apoptosis. Expression of truncated PANX1 (at the putative caspase cleavage site) resulted in a constitutively open channel. PANX1 was also important for the 'selective' plasma membrane permeability of early apoptotic cells to specific dyes. Collectively, these data identify PANX1 as a plasma membrane channel mediating the regulated release of find-me signals and selective plasma membrane permeability during apoptosis, and a new mechanism of PANX1 activation by caspases.     

Value-entanglement and the integrity of scientific research

Throughout much of the 20th century, philosophers of science maintained a position known as the value-free ideal, which holds that non-epistemic (e.g., moral, social, political, or economic) values should not influence the evaluation and acceptance of scientific results. In the last few decades, many philosophers of science have rejected this position by arguing that non-epistemic values can and should play an important role in scientific judgment and decision-making in a variety of contexts, including the evaluation and acceptance of scientific results. Rejecting the value-free ideal creates some new and vexing problems, however. One of these is that relinquishing this philosophical doctrine may undermine the integrity of scientific research if practicing scientists decide to allow non-epistemic values to impact their judgment and decision-making. A number of prominent philosophers of science have sought to show how one can reject the value-free ideal without compromising the integrity of scientific research. In this paper, we examine and critique their views and offer our own proposal for protecting and promoting scientific integrity. We argue that the literature on research ethics and its focus on adherence to norms, rules, policies, and procedures that together promote the aims of science can provide a promising foundation for building an account of scientific integrity. These norms, rules, policies, and procedures provide a level of specificity that is lacking in most philosophical discussions of science and values, and they suggest an important set of tasks for those working in science and values—namely, assessing, justifying, and prioritizing them. Thus, we argue that bringing together the literature on research ethics with the literature on science and values will enrich both areas and generate a more sophisticated and detailed account of scientific integrity.     

Human platelet 5-hydroxytryptamine receptors: binding of [3H]-lysergic acid diethylamide (LSD). Effects of chronic neuroleptic and antidepressant drug administration

Chronic treatment with phenothiazines and thioxanthenes has been found to enhance 5-HT-induced aggregation of human platelets. A method has been developed to study 5-HT2 receptor binding sites on platelets utilising [3H]-LSD and more recently 125I/LSD. Results are presented which suggest that the LSD binding site is indeed the 5-HT2 binding site and that the LSD binding characterises the specific receptor responsible for 5-HT-induced shape change and aggregation. In a group of patients receiving phenothiazines or thioxanthenes, the Bmax of LSD binding was increased. The mean binding affinity was decreased possibly due to a persistence of neuroleptic in the platelet membrane preparation. Analysis showed that this was not the reason why the mean binding capacity was increased. The results show that chronic phenothiazine and thioxanthene delta treatment 'up-regulates' platelet 5-HT2 binding sites and that this may be accompanied by increased sensitivity to platelet aggregation by 5-HT. In normal subjects desipramine treatment increased the Bmax of platelet LSD binding and this was accompanied by an increased prolactin response to tryptophan which is thought to be mediated by central 5-HT function.     

Douglas on values: From indirect roles to multiple goals

In recent papers and a book, Heather Douglas has expanded on the well-known argument from inductive risk, thereby launching an influential contemporary critique of the value-free ideal for science. This paper distills Douglas’s critique into four major claims. The first three claims provide a significant challenge to the value-free ideal for science. However, the fourth claim, which delineates her positive proposal to regulate values in science by distinguishing direct and indirect roles for values, is ambiguous between two interpretations, and both have weaknesses. Fortunately, two elements of Douglas’s work that have previously received much less emphasis (namely, her comments about the goals of scientific activity and the ethics of communicating about values) provide resources for developing a more promising approach for regulating values in science.