An investigation of the interaction between isoniazid and the contraceptive steroid norethindrone in vivo

Summary Isonicotinic acid hydrazide (isoniazid) was shown to react readily with 17-ethinyl-17-hydroxyestr-4-en-3-one (norethindrone) to form the isonicotinyl hydrazone of the steroid under conditions likely to exist in the stomach. The hydrazone was detected in guinea-pig, but not rat, plasma following its oral administration. Rat liver tissue metabolized the compound more rapidly than guinea-pig liver in vitro which probably accounts for the failure to detect the hydrazone in rat plasma.     

Allene versus acetylene in progestational steroids

In an attempt to find a side chain biologically superior to the common acetylene (e.g., 17alpha-ethynyl as in ethisterone, mestranol and ethinyl estradiol) for an orally active protestogen, 17alpha allene derivatives of norethindrone and mestranol were prepared and tested in the rabbit CLAUBERG assay, and in the rat vaginal smear assay. The minimal effective dose for norethindrone in the rabbit test was .05 mg sc for 5 days; .0025 mg for 17alpha-norethindrone-CH=C=CH2; and .005 mg for 17 alpha-norethindrone-C(CH3)=C=CH2. Similar increases in progestational activity were obtained in the antiestrogenicity and ovulation inhibiton tests. When a saturated carbon was inserted, as in 17alpha-norethindrone-CH(CH3)-CH=C=CH2, the beta allenyl derivative was completely inactive. The ED50 for mestranol in the rat vaginal smear assay (estrogenicity) was .003mg; for 17alpha-mestranol-CH=C-CH2 .01 mg; for 17alpha-mestranol-C(CH3)=C=CH2 .015 mg.     

Categorization, anomalies and the discovery of nuclear fission

The characteristics of scientific revolutions and by the same token the question of which events in the history of science deserve the name of revolutionary are controversial themes in the philosophy of science. An issue of disagreement is the question of whether or not events in which only parts of a paradigm are overthrown can truly be called a revolution, or if this term is to be reserved for the developments in which a wholesale replacement of ideas takes place. In this paper Kuhn's latest attempt to state a principle for distinguishing revolutionary developments will be reviewed, and it will be argued that certain developments entailing only partial replacements of the paradigm can be called revolutionary. The discovery of fission will serve as case study to illustrate this idea.     

Binding of D-alpha-tocopherol to rat liver nuclear components.

When D-alpha-tocopherol is administered i.v. to vitamin E deficient rats, significant amounts of this vitamin are bound to a nucleoprotein complex in hepatic nuclei, and this complex can be solubilized by high concentrations of sodium chloride (0.6 M). The bound vitamin in this complex, extractable by ethanol, was found to be identical with authentic alpha-tocopherol by thin layer chromatography.     

The molecular epidemiology of parasites.

The explosion of new techniques, made available by the rapid advance in molecular biology, has provided a battery of novel approaches and technology which can be applied to more practical issues such as the epidemiology of parasites. In this review, we discuss the ways in which this new field of molecular epidemiology has contributed to and corroborated our existing knowledge of parasite epidemiology. Similar epidemiological questions can be asked about many different types of parasites and, using detailed examples such as the African trypanosomes and the Leishmania parasites, we discuss the techniques and the methodologies that have been or could be employed to solve many of these epidemiological problems.     

基于FLUENT的NA63A系列翼型气动特性对比分析

利用计算流体力学软件FLUENT6．3．2对在风力发电领域应用较为广泛的NA63A系列翼型的外部流场进行数值模拟,采用Spalar-S．Allmaras湍流计算模型求解该系列翼型在不同攻角下的压力、速度分布。进而对NA63A系列不同翼型在相同攻角下以及网种翼型在不同攻角下的气动特性进行对比分析并总结规律,为该类翼型的性能研究提供了一定的理论依据。     

Enhancement of vertebrate cardiogenesis by a lectin from perivitelline fluid of horseshoe crab embryo

Cardiac myocytes are the first cells to differentiate during the development of a vertebrate embryo. A wide variety of molecules take part in various steps in this process. While exploring biologically active molecules from marine sources, we found that a constituent of perivitelline fluid from embryos of the Indian horseshoe crab can enhance growth and differentiation of chick embryonic heart. We have purified the factor and identified the cardiac promoting molecule to be a novel lectin. We show that this molecule influences cardiac development by increasing the number of cells constituting the heart and by modulating the expression of several cardiac development regulatory genes in chick embryos. Using mouse embryonic stem cells we show that the cardiac myocyte-enhancing capacity of this molecule extends to mammals and its effects can be blocked using methylated sugars. This molecule may prove to be an important tool in the study of cardiomyocyte differentiation.     

The molecular epidemiology of parasites

Summary The explosion of new techniques, made available by the rapid advance in molecular biology, has provided a battery of novel approaches and technology which can be applied to more practical issues such as the epidemiology of parasites. In this review, we discuss the ways in which this new field of molecular epidemiology has contributed to and corroborated our existing knowledge of parasite epidemiology. Similar epidemiological questions can be asked about many different types of parasites and, using detailed examples such as the African trypanosomes and theLeishmania parasites, we discuss the techniques and the methodologies that have been or could be employed to solve many of these epidemiological problems.     

基于数字Costas环载波同步系统的设计

发射机与接收机的相对运动产生的多普勒现象引起的频率漂移会明显地恶化系统性能,导致误码率的增加.针对此问题,设计了一个载波同步系统,采用数字Costas环载波恢复技术补偿多普勒频移.系统可以有效跟踪大多普勒频移,从而实现可靠通信.     

Detection and localization of a ribonuclease activity associated with vaccinia virus]

A ribonuclease associated with vaccinia virus can be detected when reduced concentrations of nucleotides are used for an in vitro RNA synthesis assay. The non-viral origin of this ribonuclease may be inferred from its external location and from its variable activity on different purified virus stocks. The detection of this ribonuclease activity on purified virus grown without foetal Calf serum may suggest that this enzyme is of cellular origin.     

Improved business planning through an awareness of political cycles

Can business planning be improved if more attention is paid to underlying political cycles? This paper compares practitioner and researcher perspectives on this issue. While practioners stand to gain useful insights from a careful examination of past political cycles, these insights may be disconfirmed by rigorous tests carried out by researchers. In this paper we isolate and examine five hypotheses from the literature on the political-economic cycle.     

Kuhn and the genesis of the "new historiography of science"

In this paper I identify a tension between the two sets of works by Kuhn regarding the genesis of the "new historiography of science". In the first, it could be said that the change from the traditional to the new historiography is strictly endogenous (referring to internal causes or reasons). In the second, the change is predominantly exogenous. To address this question, I draw on a text that is considered to be less important among Kuhn's works, but which, as shall be argued, allows some contact between Kuhn's two approaches via Koyré. I seek to point out and differentiate the roles of Koyré and Kuhn--from Kuhn's point of view--in the development of the historiography of science and, as a complement, present some reflections regarding the justification of the new historiography.     

The normativity of artefacts

Part of the distinction between artefacts, objects made by humans for particular purposes, and natural objects is that artefacts are subject to normative judgements. A drill, say, can be a good drill or a poor drill, it can function well or correctly or it can malfunction. In this paper I investigate how such judgements fit into the domain of the normative in general and what the grounds for their normativity are. Taking as a starting point a general characterization of normativity proposed by Dancy, I argue how statements such as ‘this is a good drill’ or ‘this drill is malfunctioning’ can be seen to express normative facts, or the content of normative statements. What they say is that a user who has a desire to achieve a particular relevant outcome has a reason to use, or not to use, the artefact in question. Next this analysis is extended to show that not just statements that say that an artefact performs its function well or poorly, but all statements that ascribe a function to an artefact can be seen as expressing a normative fact. On this approach the normativity of artefacts is analyzed in terms of reasons on grounds of practical, and to a lesser extent theoretical, rationality. I close by investigating briefly to what extent reasons on moral grounds are, in the analysis adopted here, involved in the normativity of artefacts.     

Generation of cellular immune responses to antigenic tumor peptides

Tumor immunotherapy is currently receiving close scrutiny. However, with the identification of tumor antigens and their production by recombinant means, the use of cytokines and knowledge of major histocompatibility complex (MHC) class I and class II presentation has provided ample reagents for use and clear indications of how they should be used. At this time, much attention is focused on using peptides to be presented by MHC class I molecules to both induce and be targets for CD8+ cytolytic T cells. Many peptides generated endogenously or given exogenously can enter the class I pathway, but a number of other methods of entering this pathway are also known and are discussed in detail herein. While the review concentrates on inducing cytotoxic T cells (CTLs), it is becoming increasingly apparent that other modes of immunotherapy would be desirable, such as class II presentation to induce increased helper activity (for CTL), but also activating macrophages to be effective against tumor cells.     

The possible role of glutamine in some cells of the immune system and the possible consequence for the whole animal

Glutamine is important for the function of lymphocytes and macrophages. A role for the high rate of glutamine utilisation by these cells is presented. Since muscle syntheses, stores and releases glutamine, this tissue may play a role in the immune response. Since the number of immune cells utilising glutamine may be large, the demand for glutamine from muscle, especially during trauma sepsis or burns, may be very high. A speculative suggestion is put forward that this requirement for glutamine from muscle may play a role in cachexia under some of these conditions.     

The ecological rationality of explanatory reasoning

There is growing evidence that explanatory considerations influence how people change their degrees of belief in light of new information. Recent studies indicate that this influence is systematic and may result from people’s following a probabilistic update rule. While formally very similar to Bayes’ rule, the rule or rules people appear to follow are different from, and inconsistent with, that better-known update rule. This raises the question of the normative status of those updating procedures. Is the role explanation plays in people’s updating their degrees of belief a bias? Or are people right to update on the basis of explanatory considerations, in that this offers benefits that could not be had otherwise? Various philosophers have argued that any reasoning at deviance with Bayesian principles is to be rejected, and so explanatory reasoning, insofar as it deviates from Bayes’ rule, can only be fallacious. We challenge this claim by showing how the kind of explanation-based update rules to which people seem to adhere make it easier to strike the best balance between being fast learners and being accurate learners. Borrowing from the literature on ecological rationality, we argue that what counts as the best balance is intrinsically context-sensitive, and that a main advantage of explanatory update rules is that, unlike Bayes’ rule, they have an adjustable parameter which can be fine-tuned per context. The main methodology to be used is agent-based optimization, which also allows us to take an evolutionary perspective on explanatory reasoning.     

A philosophical study of the transition from the caloric theory of heat to thermodynamics: Resisting the pessimistic meta-induction

I began this study with Laudan's argument from the pessimistic induction and I promised to show that the caloric theory of heat cannot be used to support the premisses of the meta-induction on past scientific theories. I tried to show that the laws of experimental calorimetry, adiabatic change and Carnot's theory of the motive power of heat were (i) independent of the assumption that heat is a material substance, (ii) approximately true, (iii) deducible and accounted for within thermodynamics.I stressed that results (i) and (ii) were known to most theorists of the caloric theory and that result (iii) was put forward by the founders of the new thermodynamics. In other words, the truth-content of the caloric theory was located, selected carefully, and preserved by the founders of thermodynamics.However, the reader might think that even if I have succeeded in showing that laudan is wrong about the caloric theory, I have not shown how the strategy followed in this paper can be generalised against the pessimistic meta-induction. I think that the general strategy against Laudan's argument suggested in this paper is this: the empirical success of a mature scientific theory suggests that there are respects and degrees in which this theory is true. The difficulty for — and and real challenge to — philosophers of science is to suggest ways in which this truth-content can be located and shown to be preserved — if at all — to subsequent theories. In particular, the empirical success of a theory does not, automatically, suggest that all theoretical terms of the theory refer. On the contrary, judgments of referential success depend on which theoretical claims are well-supported by the evidence. This is a matter of specific investigation. Generally, one would expect that claims about theoretical entities which are not strongly supported by the evidence or turn out to be independent of the evidence at hand, are not compelling. For simply, if the evidence does not make it likely that our beliefs about putative theoretical entities are approximately correct, a belief in those entities would be ill-founded and unjustified. Theoretical extrapolations in science are indespensable , but they are not arbitrary. If the evidence does not warrant them I do not see why someone should commit herself to them. In a sense, the problem with empricist philisophers is not that they demand that theoretical beliefs must be warranted by evidence. Rather, it is that they claim that no evidence can warrant theorretical beliefs. A realist philosopher of science would not disagree on the first, but she has good grounds to deny the second.I argued that claims about theoretical entities which are not strongly supported by the evidence must not be taken as belief-worthy. But can one sustaon the more ambitious view that loosely supported parts of a theory tend to be just those that include non-referring terms? There is an obvious excess risk in such a generalisation. For there are well-known cases in which a theoretical claim was initially weakly supported by the evidence     

海藻生物活性物质研究的回顾与展望

本文简要介绍了海藻来源的生物活性物质研究概况，并对生物技术在这一领域的应用前景做了初步的讨论与展望.作为海洋中有机物的原始生产者，海藻含有多种生物活性物质，包括抗肿瘤、抗病毒、抗菌活性物质、抗氧化剂、免疫调节剂、酶抑制剂等.而人工栽培、组织培养、细胞工程、基因工程等生物技术在海藻生物活性物质研究领域的应用将有可能为海藻生物活性物质的研究与开发提供高效费比的药源解决方案。