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1.
Transthyretin (formerly called prealbumin) plays important physiological roles as a transporter of thyroxine and retinol-binding protein. X-ray structural studies have provided information on the active conformation of the protein and the site of binding of both ligands. Transthyretin is also one of the precursor proteins commonly found in amyloid deposits. Both wild-type and single-amino-acid-substituted variants have been identified in amyloid deposits, the variants being more amyloidogenic. Sequencing of the gene and the resulting production of a transgenic mouse model have resulted in progress toward solving the mechanism of amyloid formation and detecting the variant gene in individuals at risk. Received 23 January 2001; received after revision 4 April 2001; accepted 30 April 2001 相似文献
2.
Neurotrophins are growth factors implicated in the development and maintenance of different neuronal populations in the nervous system. Neurotrophins bind to two sets of receptors, Trk receptor tyrosine kinases and the p75NTR receptor, to activate several different signaling pathways that mediate various biological functions. While Trk receptor activation has been well-studied and triggers the well-characterized Ras/Rap-MAPK, PI3K-Akt, and PLCgamma-PKC cascades, p75NTR signaling is more complex, and its in vivo significance has not yet been completely determined. In the last few years, p75NTR has received much attention mainly due to recent findings describing pro-neurotrophins as new ligands for the receptor and the ability of the receptor to form different complexes with other transmembrane proteins. This review will update the neurotrophin signaling pathways known for Trk receptors to include newly identified Trk-interacting molecules and will address surprising new findings that suggest a role for p75NTR in different receptor complexes and functions. 相似文献
3.
Roth L Koncina E Satkauskas S Crémel G Aunis D Bagnard D 《Cellular and molecular life sciences : CMLS》2009,66(4):649-666
The semaphorin family is a large group of proteins controlling cell migration and axonal growth cone guidance. These proteins
are bi-functional signals capable of growth promotion or growth inhibition. Initially described in the nervous system, the
majority of studies related to semaphorins and semaphorin signalling are nowadays performed in model systems outside the nervous
system. Here, we provide an exhaustive review of the many faces of semaphorins both during developmental, regulatory and pathological
processes. Indeed, because of their crucial fundamental roles, the semaphorins and their receptors represent important targets
for the development of drugs directed at a variety of diseases.
Received 22 August 2008; received after revision 22 September 2008; accepted 24 September 2008
L. Roth, E. Koncina, S. Satkauskas: These authors contributed equally to this work. 相似文献
4.
Alberto A. Martinez 《Annals of science》2016,73(4):345-374
This paper analyses the importance of Giordano Bruno's belief in many worlds, including the Moon, the planets and the stars, in the context of his trial by the Inquisitions in Venice and Rome. Historians have claimed that this belief was not heretical and therefore was not a major factor in Bruno's trial or execution. On the contrary, by examining neglected treatises on theology, heresies and Catholic canon law, I show that the belief in many worlds was formally heretical. Multiple Christian authorities denounced it. A systematic analysis of the extant primary sources shows that Bruno's belief in many worlds was, surprisingly, of primary importance in his trial and execution. The evidence includes recent and newly discovered primary sources. 相似文献
5.
The paper examines philosophical issues that arise in contexts where one has many different models for treating the same system. I show why in some cases this appears relatively unproblematic (models of turbulence) while others represent genuine difficulties when attempting to interpret the information that models provide (nuclear models). What the examples show is that while complementary models needn’t be a hindrance to knowledge acquisition, the kind of inconsistency present in nuclear cases is, since it is indicative of a lack of genuine theoretical understanding. It is important to note that the differences in modeling do not result directly from the status of our knowledge of turbulent flows as opposed to nuclear dynamics—both face fundamental theoretical problems in the construction and application of models. However, as we shall, the ‘problem context(s)’ in which the modeling takes plays a decisive role in evaluating the epistemic merit of the models themselves. Moreover, the theoretical difficulties that give rise to inconsistent as opposed to complementary models (in the cases I discuss) impose epistemic and methodological burdens that cannot be overcome by invoking philosophical strategies like perspectivism, paraconsistency or partial structures. 相似文献
6.
Richard Samuels 《Studies in history and philosophy of science》2010,41(3):280-293
In this paper I defend the classical computational account of reasoning against a range of highly influential objections, sometimes called relevance problems. Such problems are closely associated with the frame problem in artificial intelligence and, to a first approximation, concern the issue of how humans are able to determine which of a range of representations are relevant to the performance of a given cognitive task. Though many critics maintain that the nature and existence of such problems provide grounds for rejecting classical computationalism, I show that this is not so. Some of these putative problems are a cause for concern only on highly implausible assumptions about the extent of our cognitive capacities, whilst others are a cause for concern only on similarly implausible views about the commitments of classical computationalism. Finally, some versions of the relevance problem are not really objections but hard research issues that any satisfactory account of cognition needs to address. I conclude by considering the diagnostic issue of why accounts of cognition in general—and classical computational accounts, in particular—have faired so poorly in addressing such research issues. 相似文献
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Credibility models in actuarial science deal with multiple short time series where each series represents claim amounts of different insurance groups. Commonly used credibility models imply shrinkage of group-specific estimates towards their average. In this paper we model the claim size yu in group i and at time t as the sum of three independent components: yit = μr + δi + ?it. The first component, μt = μt?1 + mt, represents time-varying levels that are common to all groups. The second component, δi, represents random group offsets that are the same in all periods, and the third component represents independent measurement errors. In this paper we show how to obtain forecasts from this model and we discuss the nature of the forecasts, with particular emphasis on shrinkage. We also assess the forecast improvements that can be expected from such a model. Finally, we discuss an extension of the above model which also allows the group offsets to change over time. We assume that the offsets for different groups follow independent random walks. 相似文献
9.
Emilia Pedone Danila Limauro Katia D’Ambrosio Giuseppina De Simone Simonetta Bartolucci 《Cellular and molecular life sciences : CMLS》2010,67(22):3797-3814
The Thioredoxin (Trx) fold is a versatile protein scaffold consisting of a four-stranded β-sheet surrounded by three α-helices.
Various insertions are possible on this structural theme originating different proteins, which show a variety of functions
and specificities. During evolution, the assembly of different Trx fold domains has been used many times to build new multi-domain
proteins able to perform a large number of catalytic functions. To clarify the interaction mode of the different Trx domains
within a multi-domain structure and how their combination can affect catalytic performances, in this review, we report on
a structural and functional analysis of the most representative proteins containing more than one catalytically active Trx
domain: the eukaryotic protein disulfide isomerases (PDIs), the thermophilic protein disulfide oxidoreductases (PDOs) and
the hybrid peroxiredoxins (Prxs). 相似文献
10.
Why so many sperms? An essay on the arithmetic of reproduction 总被引:1,自引:0,他引:1
J Cohen 《Science progress》1969,57(225):23-41
11.
数据位众多是三值光学计算机的突出特点之一,如何有效地管理众多的数据位成为计算机科学领域的新课题.本文通过继承、更新、增补、归纳和梳理相关的研究成果,形成了比较系统的数据位管理理论和技术架构.这个框架包括下列概念和技术:1)数据位管理基本单位“算位”和“算道”,算位用于标记简单数据类型的数据位,算道用于标记复合数据类型的数据位.2)“计算量指标”用于标示一个任务的计算量规模,对大规模、中规模和小规模的任务、系统将采取不同的管理策略.3)“数据位物理形态”指出在数据传送的各个阶段数据位所占用的具体器件.4)“坏位替换”技术实现了用预留的冗余数据位及时替换失效的数据位,依靠这项技术,三值光学计算机具有对数据位软硬件故障的容错能力.5)“整体重构”技术采用定时重构所有数据位的策略,显著减少了重构过程对计算过程的打断次数.6)“数据位分配技术”将对不同规模的任务采用各不相同的规划策略.另外,文中还讨论了用这个理论指导设计三值光学计算机第三个实验系统(SDll)硬件的情况.SDll的设计目标是为探索如何应用三值光学计算机提供实验平台.SDll的光学处理器基本模块有1024个数据位,还有128个冗余数据位,而一个光学处理器可以包含16个基本模块,所以,一个SDll最多可以有16384个数据位,并有2048个冗余数据位. 相似文献
12.
The work of Thomas Kuhn has been very influential in Anglo-American philosophy of science and it is claimed that it has initiated the historical turn. Although this might be the case for English speaking countries, in France an historical approach has always been the rule. This article aims to investigate the similarities and differences between Kuhn and French philosophy of science or ‘French epistemology’. The first part will argue that he is influenced by French epistemologists, but by lesser known authors than often thought. The second part focuses on the reactions of French epistemologists on Kuhn’s work, which were often very critical. It is argued that behind some superficial similarities there are deep disagreements between Kuhn and French epistemology. This is finally shown by a brief comparison with the reaction of more recent French philosophers of science, who distance themselves from French epistemology and are more positive about Kuhn. Based on these diverse appreciations of Kuhn, a typology of the different positions within the philosophy of science is suggested. 相似文献
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The history of modern economics abounds with pleas for more pluralism as well as pleas for more unification. These seem to be contradictory goals, suggesting that pluralism and unification are mutually exclusive, or at least that they involve trade-offs with more of one necessarily being traded off against less of the other. This paper will use the example of Paul Samuelson's Foundations of Economic Analysis (1947) to argue that the relationship between pluralism and unification is often more complex than this simple dichotomy suggests. In particular, Samuelson's Foundations is invariably presented as a key text in the unification of modern economics during the middle of the twentieth century; and in many ways that is entirely correct. But Samuelson's unification was not at the theoretical (causal and explanatory) level, but rather at the purely mathematical derivational level. Although this fact is recognized in the literature on Samuelson, what seems to be less recognized is that for Samuelson, much of the motivation for this unification was pluralist in spirit: not to narrow scientific economics into one single theory, but rather to allow for more than one theory to co-exist under a single unified derivational technique. This hidden pluralism will be discussed in detail. The paper concludes with a discussion of the implications for more recent developments in economics. 相似文献
15.
J. -Y. Wu J. A. London D. Zecevic H. -P. Höpp L. B. Cohen Chun Xiao 《Cellular and molecular life sciences : CMLS》1988,44(5):369-376
Summary Optical methods for monitoring neuron activity were developed because these methods lend themselves to simultaneous multiple-site measurements. With the use of new voltage-sensitive dyes, the dye-related pharmacology and photodynamic damage appear to be relatively unimportant. Using multiple-site measurements made with a 124-element photodiode array, we estimated that approximately 30 of the 200 neurons present in theNavanax buccal ganglion make action potentials during feeding and that approximately 300 of the 1100 neurons present in theNavanax buccal ganglion make are active during the gill-withdrawal reflex. The fact that a light mechanical touch to the siphon skin activated such a large number of neurons in the abdominal ganglion suggests that understanding the neuronal basis of the gill-withdrawal reflex and its behavioral plasticity may be forbiddingly difficult. 相似文献
16.
Optical methods for monitoring neuron activity were developed because these methods lend themselves to simultaneous multiple-site measurements. With the use of new voltage-sensitive dyes, the dye-related pharmacology and photodynamic damage appear to be relatively unimportant. Using multiple-site measurements made with a 124-element photodiode array, we estimated that approximately 30 of the 200 neurons present in the Navanax buccal ganglion make action potentials during feeding and that approximately 300 of the 1100 neurons present in the Aplysia abdominal ganglion are active during the gill-withdrawal reflex. The fact that a light mechanical touch to the siphon skin activated such a large number of neurons in the abdominal ganglion suggests that understanding the neuronal basis of the gill-withdrawal reflex and its behavioral plasticity may be forbiddingly difficult. 相似文献
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M. Kormano A. I. Koskimies R. L. Hunter 《Cellular and molecular life sciences : CMLS》1971,27(12):1461-1463
Zusammenfassung Die Flüssigkeit in den Hodenkanälchen enthielt mehrere Proteine, die im Serum oder in der Hodenlymphe nicht nachweislich waren. Nur von einigen der Serumproteine waren in der Flüssigkeit der Hodenkanälchen schwache elektrophoretische Bänder zu sehen.
Supported by a grant from the National Research Council for Medical Sciences, Helsinki, Finland.
On sabbatical leave from the Department of Human Anatomy, School of Medicine, University of California, Davis (California 95616, USA). 相似文献
Supported by a grant from the National Research Council for Medical Sciences, Helsinki, Finland.
On sabbatical leave from the Department of Human Anatomy, School of Medicine, University of California, Davis (California 95616, USA). 相似文献
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Samuel CS Hewitson TD Unemori EN Tang ML 《Cellular and molecular life sciences : CMLS》2007,64(12):1539-1557
The peptide hormone relaxin is emerging as a multi-functional factor in a broad range of target tissues including several
non-reproductive organs, in addition to its historical role as a hormone of pregnancy. This review discusses the evidence
that collectively demonstrates the many diverse and vital roles of relaxin: the homeostatic role of endogenous relaxin in
mammalian pregnancy and ageing; its gender-related effects; the therapeutic effects of relaxin in the treatment of fibrosis,
inflammation, cardioprotection, vasodilation and wound healing (angiogenesis) amongst other pathophysiological conditions,
and its potential mechanism of action. Furthermore, translational issues using experimental models (to humans) and its use
in various clinical trials, are described, each with important lessons for the design of future trials involving relaxin.
The diverse physiological and pathological roles for relaxin have led to the search for its significance in humans and highlight
its potential as a drug of the future.
Received 12 December 2006; received after revision 12 February 2007; accepted 15 March 2007 相似文献