This book is of little interest except to those tracing back the neo-scholastic sources of such figures as Maréchal, Coreth, Rahner, et al. The introductory essay by G. Isaye, supposedly designed to give a summary description of Scheurer's method, is a masterpiece of obscure writing even for those acquainted with neoscholastic jargon. The rest of the volume consists of twelve very desultory essays by Scheurer. In these essays Scheurer struggles to pour the philosophy of the ego à la Kant and (...) his successors into scholastic molds. This synthesis is done in the name of the transcendental method, but what results is historically dubious and philosophically tortured. Though ambiguities abound, Scheurer was ahead of most of his scholastic contemporaries in that he tried to come to grips with Kant and to see in Kant someone more than the malin genie of modern philosophy. Unfortunately, the editor does not date Scheurer's essays and one, therefore, cannot determine whether Scheurer first influenced Maréchal or vice-versa--D. J. M. B. (shrink)

In his foreword, Brand Blanshard provides the suitable justification for publishing yet one more book on Berkeley: Berkeley is "curiously modern," and philosophically acute. Twelve competent essays, contributed by as many scholars, testify to the accuracy of Blanshard's judgment. These twelve scholars, all of whom rely on the Luce-Jessop definitive edition, touch upon the major issues of Berkeley's philosophy: perception, substance, spirit, and God. Differences in interpretation are everywhere evident, but Berkeley is nowhere given facile treatment or quick dismissal. Of (...) the many good essays, Ian T. Ramsey's on "Berkeley and the Possibility of an Empirical Metaphysics" deserves close attention. Ramsey argues that Berkeley's doctrine of will, soul, mind, etc., should be viewed as forms of personal activity and not on the analogy of Locke's ideas. T. E. Jessop contributes a useful bibliography as well as an essay on "Berkeley as Religious Apologist." The only, very minor, flaw in this distinguished volume is that the editor's own essay, the twelfth, "Berkeley and his Modern Critics" might have been better placed immediately following the foreward.--D. J. M. B. (shrink)

This book is of little interest except to those tracing back the neo-scholastic sources of such figures as Maréchal, Coreth, Rahner, et al. The introductory essay by G. Isaye, supposedly designed to give a summary description of Scheurer's method, is a masterpiece of obscure writing even for those acquainted with neoscholastic jargon. The rest of the volume consists of twelve very desultory essays by Scheurer. In these essays Scheurer struggles to pour the philosophy of the ego à la Kant and (...) his successors into scholastic molds. This synthesis is done in the name of the transcendental method, but what results is historically dubious and philosophically tortured. Though ambiguities abound, Scheurer was ahead of most of his scholastic contemporaries in that he tried to come to grips with Kant and to see in Kant someone more than the malin genie of modern philosophy. Unfortunately, the editor does not date Scheurer's essays and one, therefore, cannot determine whether Scheurer first influenced Maréchal or vice-versa--D. J. M. B. (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)

Loop regions in proteins have traditionally been described as ‘random coil’, although they are known to adopt well‐defined conformations in most globular proteins. In this contribution we summarize the results of detailed analysis of the structures and sequences of these loop regions in proteins of known three‐dimensional structure. We also describe how these results can be used as an aid to protein design, modification and modelling.

The present review highlights an association between autism, Alzheimer disease , and fragile X syndrome . We propose a conceptual framework involving the amyloid-beta peptide , Abeta precursor protein , and fragile X mental retardation protein based on experimental evidence. The anabolic effect of the secreted alpha form of the amyloid-beta precursor protein may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPalpha levels associate with more severe symptoms of (...) autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 . Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPalpha level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPalpha and production of insoluble Abeta would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism. (shrink)

Alzheimer's disease is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-beta peptide . The rate-limiting step in the production of Abeta is the processing of Abeta precursor protein by beta-site APP-cleaving enzyme . Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Abeta within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was (...) suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of beta-galactoside alpha-2,6-sialyltransferase I . In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future. (shrink)

A superconducting transition temperature as high as 100 K was recently discovered in one monolayer FeSe grown on SrTiO3. The discovery ignited efforts to identify the mechanism for the markedly enhanced Tc from its bulk value of 8 K. There are two main views about the origin of the Tc enhancement: interfacial effects and/or excess electrons with strong electron correlation. Here, we report the observation of superconductivity below 20 K in surface electron-doped bulk FeSe. The doped surface layer possesses all (...) the key spectroscopic aspects of the monolayer FeSe on SrTiO3. Without interfacial effects, the surface layer state has a moderate Tc of 20 K with a smaller gap opening of 4.2 meV. Our results show that excess electrons with strong correlation cannot induce the maximum Tc, which in turn reveals the need for interfacial effects to achieve the highest Tc in one monolayer FeSe on SrTiO3. (shrink)

Recent progress in artificial intelligence has renewed interest in building systems that learn and think like people. Many advances have come from using deep neural networks trained end-to-end in tasks such as object recognition, video games, and board games, achieving performance that equals or even beats that of humans in some respects. Despite their biological inspiration and performance achievements, these systems differ from human intelligence in crucial ways. We review progress in cognitive science suggesting that truly human-like learning and thinking (...) machines will have to reach beyond current engineering trends in both what they learn and how they learn it. Specifically, we argue that these machines should build causal models of the world that support explanation and understanding, rather than merely solving pattern recognition problems; ground learning in intuitive theories of physics and psychology to support and enrich the knowledge that is learned; and harness compositionality and learning-to-learn to rapidly acquire and generalize knowledge to new tasks and situations. We suggest concrete challenges and promising routes toward these goals that can combine the strengths of recent neural network advances with more structured cognitive models. (shrink)

Our hospital routine requires that all new admissions must be asked about their code status. It is not uncommon for an otherwise healthy patient to request that a do-not-resuscitate order be placed in their chart. Presumably, these patients who wish to have a DNR order are acting on the belief that should an unforeseen, irreversible condition occur that leads to a cardiac arrest, they would not want to undergo resuscitation. Tragically, we have witnessed several instances in which potentially life-saving interventions (...) were withheld in viable patients in non-arrest settings for reversible conditions because the patients had a DNR order in the chart. Unfortunately, this happens when the treating physicians are not aware of the limited scope of a DNR order and instead use the order as a blanket prohibition against all components of resuscitation. This communication failure is due to misconceptions that patients and their physicians have with regard to such orders. The medical community is well overdue to improve the end-of-life decisions offered to patients beyond relying on the outdated term DNR.LIMITATIONS OF DNR ORDERSDespite the major advances in critical care medicine in the past few decades, doctors have not substantially improved their ability to address end-of-life decisions any better than by using the all-encompassing term DNR. Currently, the term is generally accepted as an order to prohibit the use of interventions to reverse a cardiac or pulmonary arrest.1 2 What is frequently forgotten with the DNR order is that …. (shrink)

Argumentation as the public exchange of reasons is widely thought to enhance deliberative interactions that generate and justify reasonable public policies. Adopting an argumentation-theoretic perspective, we survey the norms that should govern public argumentation and address some of the complexities that scholarly treatments have identified. Our focus is on norms associated with the ideals of correctness and participation as sources of a politically legitimate deliberative outcome. In principle, both ideals are mutually coherent. If the information needed for a correct deliberative (...) outcome is distributed among agents, then maximising participation increases information diversity. But both ideals can also be in tension. If participants lack competence or are prone to biases, a correct deliberative outcome requires limiting participation. The central question for public argumentation, therefore, is how to strike a balance between both ideals. Rather than advocating a preferred normative framework, our main purpose is to illustrate the complexity of this theme. (shrink)

In list-method directed forgetting, reexposure to forgotten List 1 items has been shown to reduce directed forgetting. proposed that reexposure to a few List 1 items only during a direct test of memory reinstates the entire List 1 episode. In the present experiments, part-list reexposure in the context of indirect as well as direct memory tests reduced directed forgetting. Directed forgetting was reduced when 50% or more of the items were reexposed, and was intact when only 25% were reexposed. Furthermore, (...) part-list reexposure appeared to reinstate only reexposed items-not the entire List 1 episode. (shrink)

To localize wheat ESTs on chromosomes, 882 homoeologous group 6-specific ESTs were identified by physically mapping 7965 singletons from 37 cDNA libraries on 146 chromosome, arm, and sub-arm aneuploid and deletion stocks. The 882 ESTs were physically mapped to 25 regions flanked by 23 deletion breakpoints. Of the 5154 restriction fragments detected by 882 ESTs, 2043 were localized to group 6 chromosomes and 806 were mapped on other chromosome groups. The number of loci mapped was greatest on chromosome 6B and (...) least on 6D. The 264 ESTs that detected orthologous loci on all three homoeologs using one restriction enzyme were used to construct a consensus physical map. The physical distribution of ESTs was uneven on chromosomes with a tendency toward higher densities in the distal halves of chromosome arms. About 43% of the wheat group 6 ESTs identified rice homologs upon comparisons of genome sequences. Fifty-eight percent of these ESTs were present on rice chromosome 2 and the remaining were on other rice chromosomes. Even within the group 6 bins, rice chromosomal blocks identified by 1-6 wheat ESTs were homologous to up to 11 rice chromosomes. These rice-block contigs were used to resolve the order of wheat ESTs within each bin. (shrink)

In this paper, we examine how organizations’ impression management evolves in response to rising stakeholder pressures regarding organizations’ corporate responsibility initiatives. We conducted a comparative case study analysis over a period of 13 years for two organizations—Exxon and BP—that took extreme initial stances on climate change. We found that as stakeholder pressures rose, their IM tactics unfolded in four phases: advocating the initial stance, sensegiving to clarify the initial stance, image repairing, and adjusting the stance. Taken together, our analysis of (...) IM over these four phases provides three key insights about the evolution of IM in the face of rising pressures. First, when faced with stakeholder pressures, it seems that organizations do not immediately resort to conforming but tend to give in gradually when pressures increase and start to come from relatively powerful stakeholders. Second, evolution of IM seems to be characterized by path dependence, i.e., even as organizations’ positions evolve, they continue to show their conviction in their initial positions and try to convey that their subsequent positions flow logically from the previous ones. Finally, IM involves navigation between symbolism and substance, and companies tend to strive toward harmonizing their symbolic and substantive actions as stakeholder pressure increases. (shrink)