String theory,Einstein, and the identity of physics: Theory assessment in absence of the empirical

String theorists are certain that they are practicing physicists. Yet, some of their recent critics deny this. This paper argues that this conflict is really about who holds authority in making rational judgment in theoretical physics. At bottom, the conflict centers on the question: who is a proper physicist? To illustrate and understand the differing opinions about proper practice and identity, we discuss different appreciations of epistemic virtues and explanation among string theorists and their critics, and how these have been sourced in accounts of Einstein's biography. Just as Einstein is claimed by both sides, historiography offers examples of both successful and unsuccessful non-empirical science. History of science also teaches that times of conflict are often times of innovation, in which novel scholarly identities may come into being. At the same time, since the contributions of Thomas Kuhn historians have developed a critical attitude towards formal attempts and methodological recipes for epistemic demarcation and justification of scientific practice. These are now, however, being considered in the debate on non-empirical physics.     

Retrograde transport of endocytosed Shiga toxin to the endoplasmic reticulum.

Shiga toxin and some other protein toxins that act on targets in the cytosol have previously been shown to enter the trans-Golgi network. Transport by this route may be necessary for translocation of the toxin to the cytosol and for intoxication, but it is not known whether the enzymatically active part of the toxins actually enters the cytosol from the trans-Golgi network. It has been suggested that such toxins are transported in a retrograde manner to the endoplasmic reticulum and that translocation occurs in this organelle, but retrograde transport of endocytosed material beyond the trans-Golgi network has never been demonstrated. Here we show that in butyric acid-treated A431 cells endocytosed Shiga toxin is not only transported to the trans-Golgi network, but also to all Golgi stacks, to the endoplasmic reticulum and to the nuclear envelope. Furthermore, butyric acid sensitizes the cells to Shiga toxin, which is consistent with the possibility that retrograde transport is required for translocation of the toxin to the cytosol.     

Chromosomal localization of a unique gene by non-autoradiographic in situ hybridization

During the past few years, several methods have been developed for the detection of specific nucleic acid sequences by in situ hybridization using non-radioactive labels such as fluorochromes, cytochemically detectable enzymes and electron-dense markers. These methods are preferable to autoradiography in terms of speed of performance and topological resolution. Their limited sensitivity, however, has so far restricted their use to the detection of repeated sequences. Here we report single gene detection with a procedure using 2-acetylaminofluorene (AAF)-modified probes, immunoperoxidase cytochemistry and reflection-contrast microscopy. We confirmed the autoradiographic data on the localization of the human thyroglobulin (Tg) gene to the distal end of the long arm of chromosome 8. A mixture of cosmid cHT2-derived subclones of the 3' part of the Tg gene, 22.3 kilobase pairs (kbp) in total, was used as a hybridization probe. This procedure can be used to map other unique sequences, if genomic clones are available from which clones with an appropriate amount of inserts can be isolated.     

In vitro protein synthesis and α amylase activity in F cells from hepatopancreas ofPalaemon serratus (Crustacea; Decapoda)

In crustaceans, all the steps in the assimilation of food take place in the hepatopancreas. To facilitate the study of this organ, a method for the dissociation of cell types was developed. The hepatopancreas of the prawnPalaemon serratus was mechanically dissociated and the cells separated by Percoll density-gradient centrifugation. The E and R cells had similar densities of around 1.05 g/ml. The F cells were separated into two distinct fractions with densities of 1.075 and 1.082 g/ml. The B cells sedimented at a density of 1.12 g/ml. The ratio between the two populations of F cells was found to vary during the intermolt cycle while B cells disappeared after the molt. When the density gradient fractions were incubated with³H-leucine, incorporation was highest in the F cell fractions. Measurements of -amylase activity, indicated that the two populations of F cells may be derived from the same cell type.     

Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid

Cellulose is the most abundant renewable carbon resource on earth and is an indispensable raw material for the wood, paper, and textile industries. A model system to study the mechanism of cellulose biogenesis is the bacterium Acetobacter xylinum which produces pure cellulose as an extracellular product. It was from this organism that in vitro preparations which possessed high levels of cellulose synthase activity were first obtained in both membranous and soluble forms. We recently demonstrated that this activity is subject to a complex multi-component regulatory system, in which the synthase is directly affected by an unusual cyclic nucleotide activator enzymatically formed from GTP, and indirectly by a Ca (2+) -sensitive phosphodiesterase which degrades the activator. The cellulose synthase activator (CSA) has now been identified as bis-(3' 5')-cyclic diguanylic acid (5'G3'p5'G3'p) on the basis of mass spectroscopic data, nuclear magnetic resonance analysis and comparison with chemically synthesized material. We also report here on intermediary steps in the synthesis and degradation of this novel circular dinucleotide, which have been integrated into a model for the regulation of cellulose synthesis.     

Transplantation of human cortex with Alzheimer's disease into rat occipital cortex; a model for the study of Alzheimer disease

Summary Senile dementia of the Alzheimer type (SDAT) is a major problem in the human senescent population. As this pathology cannot be reproduced in animals, research into its development is greatly impeded. The technique of implantation of the nervous tissue has been utilized in order to establish an animal model and to test the possible existence of a transmissible agent. When human temporal cortex with Alzheimer's disease is implanted in the occipital cortex of 7-week-old rats, human cerebral tissue containing abundant tangles induces in the receiver cortex a reactive fibrous gliosis. In the processes of the astrocytes, twisted filaments are evident among bundles of normal filaments. These alterations could be induced by the metabolising of abnormal filament subunits or by some infectious agent introduced by the implant.This study is supported by grant No. 2.4517.82 of Fonds de la Recherche Fondamentale Collective of Belgium.     

数位时代图书馆馆员专业知能发展之研究——以逢甲大学为例

受到资讯媒体新科技影响 ,图书馆读者使用行为已从单一的馆藏利用 ,转为期望图书馆提供更多元化的服务 ;另外在财政紧缩 资源扩增 人力不足等因素下 ,图书馆提供各类型服务的运作模式也受到相当的冲击 ,图书馆为提供以读者为道向的服务 ,必需付出许多努力并改变服务哲学 ,因而图书馆馆员的专业知能发展要不断提升才能因应数位时代的环境改变 ,并提供读者一个优质的资讯服务 ,发挥图书馆LearningResourceCenter学习资源中心的角色 .本研究主要探讨图书馆如何在有限资源下 ,有系统地规划发展馆员专业知能 ,并且利用那一种方法可以最有效率、花费最少成本达到最大的馆员能力提升效果 ,根据文献探讨以及学习行为方法理论 ,提出一个适合发展馆员专业知能的模式 (Approachmodel) ,通过探讨逢甲大学图书馆的两个专案其馆员专业知能转变的历程 ,检视了此发展模式的成效 ,并提出未来该模式可再改进的方向及建议     

On the origins and foundations of Laplacian determinism

In this paper I examine the foundations of Laplace’s famous statement of determinism in 1814, and argue that rather than derived from his mechanics, this statement is based on general philosophical principles, namely the principle of sufficient reason and the law of continuity. It is usually supposed that Laplace’s statement is based on the fact that each system in classical mechanics has an equation of motion which has a unique solution. But Laplace never proved this result, and in fact he could not have proven it, since it depends on a theorem about uniqueness of solutions to differential equations that was only developed later on. I show that the idea that is at the basis of Laplace’s determinism was in fact widespread in enlightenment France, and is ultimately based on a re-interpretation of Leibnizian metaphysics, specifically the principle of sufficient reason and the law of continuity. Since the law of continuity also lies at the basis of the application of differential calculus in physics, one can say that Laplace’s determinism and the idea that systems in physics can be described by differential equations with unique solutions have a common foundation.     

The stoichiometry of peptide-heparan sulfate binding as a determinant of uptake efficiency of cell-penetrating peptides

Binding to negatively charged heparan sulfates (HS) at the cell surface is considered the first step in the internalization of cationic cell-penetrating peptides (CPPs). However, little is known about the relation of the characteristics of the HS-CPP interaction such as affinity, stoichiometry, and clustering with uptake. In this study, we investigated a collection of mutants of a cyclic CPP derived from human lactoferrin with respect to HS binding and uptake. The thermodynamic parameters of HS binding were determined by isothermal titration calorimetry, clustering of HS was investigated by dynamic light scattering, and cellular uptake by flow cytometry and confocal microscopy. Whereas mutations of non-arginine amino acids that are conserved across lactoferrins of different mammalia only had a minor effect on uptake efficiency, changes in the number of arginine residues influenced the uptake significantly. In general, introduction of arginine residues and cyclization improved the HS affinity and the ability to cluster HS. In particular, there was a strong negative correlation between stoichiometry and uptake, indicating that crosslinking of HS is the driving force for the uptake of arginine-rich CPPs. Using glycan microarrays presenting a collection of synthetic HS, we show that a minimal chain length of HS is required for peptide binding.     

Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4

P4-ATPases are lipid flippases that catalyze the transport of phospholipids to create membrane phospholipid asymmetry and to initiate the biogenesis of transport vesicles. Here we show, for the first time, that lipid flippases are essential to dampen the inflammatory response and to mediate the endotoxin-induced endocytic retrieval of Toll-like receptor 4 (TLR4) in human macrophages. Depletion of CDC50A, the β-subunit that is crucial for the activity of multiple P4-ATPases, resulted in endotoxin-induced hypersecretion of proinflammatory cytokines, enhanced MAP kinase signaling and constitutive NF-κB activation. In addition, CDC50A-depleted THP-1 macrophages displayed reduced tolerance to endotoxin. Moreover, endotoxin-induced internalization of TLR4 was strongly reduced and coincided with impaired endosomal MyD88-independent signaling. The phenotype of CDC50A-depleted cells was also induced by separate knockdown of two P4-ATPases, namely ATP8B1 and ATP11A. We conclude that lipid flippases are novel elements of the innate immune response that are essential to attenuate the inflammatory response, possibly by mediating endotoxin-induced internalization of TLR4.