On the ethics of extending human life: healthy people have a right to carry on livingHumanity has long demonstrated a paradoxical ambivalence concerning the extension of a healthy human lifespan. Modest health extension has been universally sought, whereas extreme health extension has been regarded as a snare and delusion—a dream beyond all others at first blush, but actually something we are better off without. The prevailing pace of biotechnological progress is bringing ever closer the day when humanity will be able (...) to act on the latter view by rejecting a clear and present opportunity for much longer healthy lives. Indeed, some biogerontologists contend that that day has already arrived, to the extent that our hesitation in embarking on a vigorous “war on ageing” is already delaying the point at which a cure for ageing will be developed. Here I consider whether our present caution concerning the wisdom of truly curing ageing is likely to survive the increased scrutiny that it will receive in coming years as a result of these technical advances. I conclude that it will not, because of its irreconcilability with values that are more deeply held by the large majority of humanity than any values that argue against the quest for a cure. I further conclude that all the major current reasons given for not curing ageing are mere crutches to help us cope with the immutability of ageing that we have been brought up to accept. Our failure to set aside such irrationality is already shortening potential longevity—quite probably of those already alive today—to a staggering degree. Once we realise this, our determination to consign human ageing to history will be second …. (shrink)

Editors’ note: These four interrelated discussions of the role of the cerebellum in coordinating emotional and higher cognitive functions developed out of a workshop presented by the four authors for the 2000 Conference of the Cognitive Science Society at the University of Pennsylvania. The four interrelated discussions explore the implications of the recent explosion of cerebellum research suggesting an expanded cerebellar role in higher cognitive functions as well as in the coordination of emotional functions with learning, logical thinking, perceptual consciousness, (...) and action planning. (shrink)

The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags accounting for 2266 restriction fragments on the homoeologous group 3 chromosomes of hexaploid wheat. Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the (...) chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes ∼21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected. (shrink)

Over recent years, evidence has been accumulating in favour of the free radical theory of aging, first proposed by Harman. Despite this, an understanding of the mechanism by which cells might succumb to the effects of free radicals has proved elusive. This paper proposes such a mechanism, based on a previously unexplored hypothesis for the proliferation of mutant mitochondrial DNA: that mitochondria with reduced respiratory function, due to a mutation or deletion affecting the respiratory chain, suffer less frequent lysosomal degradation, (...) because they inflict free radical damage more slowly on their own membranes. Once such a mutation occurs in a mitochondrion of a non‐dividing cell, therefore, mitochondria carrying it will rapidly populate that cell, thereby destroying the cell's respiratory capability. The accumulation of cells that have undergone this transition results in aging at the organismal level. The consistency of the hypothesis with known facts is discussed, and technically feasible tests are suggested, of both the proposed mechanism and its overall contribution to mammalian aging. (shrink)

The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY (...) Acad Sci 959, 452–462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it. BioEssays 24:667–676, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

It is time for the noon conference. Your job is to impart a career-changing experience in ethics to a group of students and interns gathered from four different schools with varying curriculums in ethics. They have just finished 1½ h of didactic sessions and lunch. One third of them were on call last night. Your first job is to keep them awake. The authors argue that this “tragic case” approach to ethics education is of limited value because it limits understanding (...) of moral problems to dilemmas; negates the moral agency of the student; encourages solutions that are merely intellectual; and suggests that ethical encounters are a matter for experts. The authors propose an alternative that focuses on three issues: the provider-patient relationship, the relationships between providers in the everyday world of health work and, the social position of healthcare providers in society. In this approach, teachers are not experts but more like guides on a journey who help students to learn that much of ethical practice comprises living through difficult situations of caring for vulnerable others and who help students to navigate some of these difficulties. (shrink)

Electrical resistivity and ac-calorimetric measurements reveal a complex magnetic phase diagram for single crystals of the ferromagnetic Kondo-lattice compound CeAgSb2 at high pressures up to 80 kbar. The ferromagnetic order at TC = 9.6 K at ambient pressure is completely suppressed at a critical pressure PC = 35 kbar. Another magnetic transition, possibly antiferromagnetic, found above 27 kbar, attains a maximum value TN 6 K at 44 kbar and then appears to be completely suppressed by 50 kbar. Thermodynamic and transport (...) measurements in the ferromagnetic state indicate an energy gap Δ 30 K in the spin-wave excitation spectrum at ambient pressure which decreases to Δ 10 K at P = 30 kbar. No superconductivity is observed at ambient pressure above T 0.1 K, under applied pressure in the ferromagnetic state (P = 28.5 kbar), nor in the antiferromagnetic state (P = 33 − 46 kbar) above 0.3 K. © 2003 The American Physical Society. (shrink)

BACKGROUND: Serotonin transporter promoter genotype appears to increase risk for depression in the context of stressful life events. However, the effects of this genotype on measures of stress sensitivity are poorly understood. Therefore, this study examined whether 5-HTTLPR genotype was associated with negative information processing biases in early childhood. METHOD: Thirty-nine unselected seven-year-old children completed a negative mood induction procedure and a Self-Referent Encoding Task designed to measure positive and negative schematic processing. Children were also genotyped for the 5-HTTLPR gene. (...) RESULTS: Children who were homozygous for the short allele of the 5-HTTLPR gene showed greater negative schematic processing following a negative mood prime than those with other genotypes. 5-HTTLPR genotype was not significantly associated with positive schematic processing. LIMITATIONS: The sample size for this study was small. We did not analyze more recently reported variants of the 5-HTTLPR long alleles. CONCLUSIONS: 5-HTTLPR genotype is associated with negative information processing styles following a negative mood prime in a non-clinical sample of young children. Such cognitive styles are thought to be activated in response to stressful life events, leading to depressive symptoms; thus, cognitive styles may index the "stress-sensitivity" conferred by this genotype. (shrink)

We apply an online optimization process based on machine learning to the production of Bose-Einstein condensates. BEC is typically created with an exponential evaporation ramp that is optimal for ergodic dynamics with two-body s-wave interactions and no other loss rates, but likely sub-optimal for real experiments. Through repeated machine-controlled scientific experimentation and observations our ’learner’ discovers an optimal evaporation ramp for BEC production. In contrast to previous work, our learner uses a Gaussian process to develop a statistical model of the (...) relationship between the parameters it controls and the quality of the BEC produced. We demonstrate that the Gaussian process machine learner is able to discover a ramp that produces high quality BECs in 10 times fewer iterations than a previously used online optimization technique. Furthermore, we show the internal model developed can be used to determine which parameters are essential in BEC creation and which are unimportant, providing insight into the optimization process of the system. (shrink)

From A. N. Whitehead, his senior collaborator in the classic work on mathematical logic which established his philosophical reputation, Bertrand Russell once provoked the exasperated remark: “Bertie, you’re an aristocrat, not a gentleman”. To-day having matured in the lived experience of eighty-five years and having spanned this century with widely-publicised books, articles and lectures, Russell remains a living paradox in whom the cool logician, the social prophet and the tantalising polemist have yet to achieve integration. Issuing from an established intellectual (...) family with a precociously questioning mind and a moral courage equal to the assertion of any truth, educating himself to a razor-keen mind and a mastery of lucid prose, he has adopted the public role of a witty sophist as well as an iconoclast angry with conservative convention in moral, social and religious conduct. Theoretically practical conduct is a realm of private feeling and not of objective truth in his philosophy, which he implements with literal freedom. Nevertheless he must be conscious that his polemic often falls short of the standard of a disciplined respect for truth, though he might explain away this defect by referring to the accepted rules of the game which he plays…hard. Yet his biographer notes that he resents criticism of his moral and social writings more than of his purely academic work. And his aim, as expressed in a letter from Brixton prison in 1918 where an embarrassed government confined his biting pacifism, is constructive: “There is a little wisdom in the world; Heraclitus, Spinoza, and a saying here and there. I want to add to it, even if only ever so little”. (shrink)

Polyclonal antibodies raised against the human erythrocyte nucleoside transporter were used to investigate the distribution of the nucleoside transporters in the placenta. Immunoblots of brush-border membranes isolated from the human syncytiotrophoblast revealed a cross-reactive species that co-migrated with the erythrocyte nucleoside transporter as a broad band of apparent M(r) 55,000. In contrast, no labelling was detected in basal membranes containing a similar number of equilibrative nucleoside transporters as assessed by nitrobenzylthioinosine (NBMPR)-binding. The absence of cross-reactive epitopes in basal membranes and (...) their presence in brush-border membranes was confirmed by confocal immunofluorescence microscopy. The results suggest that at least two isoforms of the NBMPR-sensitive nucleoside transporter are present in the human placenta. The lumenal surfaces of fetal capillaries, small placental vessels and umbilical vein ware also strongly labelled by the antibody, a finding that suggests that the high fetal-placental adenosine uptake previously reported is due to endothelial transporters. (shrink)