Developing an Antibody–Drug Conjugate Approach to Selective Inhibition of an Extracellular Protein

Antibody–drug conjugates (ADCs) are a growing class of therapeutics that harness the specificity of antibodies and the cell-killing potency of small-molecule drugs. Beyond cytotoxics, there are few examples of the application of an ADC approach to difficult drug discovery targets. Here, we present the initial development of a non-internalising ADC, with a view to selectively inhibiting an extracellular protein. Employing the wellinvestigated matrix metalloproteinase-9 (MMP-9) as our model, we adapted a broad-spectrum, nonselective MMP inhibitor for conjugation and linked this to a MMP-9-targeting antibody. The resulting ADC fully inhibits MMP-9, and ELISA results suggest antibody targeting can direct a nonselective inhibitor.     

Dietary analysis and patterns of nutritional supplement use in normal and age-related macular disease affected subjects: a prospective cross-sectional study

Background  

Poor diet is thought to be a risk factor for many diseases, including age-related macular disease (ARMD), which is the leading cause of blind registration in those aged over 60 years in the developed world. The aims of this study were 1) to evaluate the dietary food intake of three subject groups: participants under the age of 50 years without ARMD (U50), participants over the age of 50 years without ARMD (O50), and participants with ARMD (AMD), and 2) to obtain information on nutritional supplement usage.     

Metric and reference factors in minimum error rate training

In Minimum Error Rate Training (MERT), Bleu is often used as the error function, despite the fact that it has been shown to have a lower correlation with human judgment than other metrics such as Meteor and Ter. In this paper, we present empirical results in which parameters tuned on Bleu may lead to sub-optimal Bleu scores under certain data conditions. Such scores can be improved significantly by tuning on an entirely different metric altogether, e.g. Meteor, by 0.0082 Bleu or 3.38% relative improvement on the WMT08 English–French data. We analyze the influence of the number of references and choice of metrics on the result of MERT and experiment on different data sets. We show the problems of tuning on a metric that is not designed for the single reference scenario and point out some possible solutions.     

The Reactivity of Difluorocarbene with Hydroxylamines: Synthesis of Carbamoyl Fluorides

Carbamoyl fluorides are formed in reactions of hydroxylamines with difluorocarbene generated from sodium bromodifluoroacetate as readily available and non‐toxic carbene precursor. The process shows a high functional group tolerance, and the reaction path has been rationalized by computational calculations.

     

Submicron silicon bipolar master-slave D-type flip-flop for use as 8.1 Gbit/s decision circuit and 11.2 Gbit/s demultiplexer

The authors have designed and implemented a submicron silicon bipolar master-slave D-type flip-flop integrated circuit which can be used either as a decision circuit or a demultiplexer, operating at data rates as high as 8.1 and 11.2 Gbit/s, respectively. The circuit was fabricated using a 0.6 mu m, nonpolysilicon emitter technology, occupying an area of 0.8 mm*0.9 mm, and dissipating 410 mW of power.<>     

NATIONAL INSTITUTIONAL FRAMEWORKS AND THE HYBRIDIZATION OF ENTREPRENEURIAL BUSINESS MODELS: THE GERMAN AND UK BIOTECHNOLOGY SECTORS

Given what institutional scholars have described as an inhospitable institutional climate for entrepreneurial business, why has the German biotechnology industry suddenly taken off, while in the UK, where a ''correct'' institutional architecture exists, has the industry shown signs of stagnation? To explain these trends the article develops a firm-centered approach, recognizing that firms work with institutional frameworks - often with help from public policies - to create new business strategies. The argument is developed that such processes are associated with the ''hybridization'' of business strategies at the micro level, combined with the generation of new constellations of particular institutional frameworks within relatively stable national models.     

Biographical data in employment selection: Can validities be made generalizable?

The hypothesis was examined that organizational specificity of biodata validity results from the methods typically used to select and key items. In this study, items were initially screened for job relevance, keying was based on large samples from multiple organizations, and items were retained only if they showed validity across organizations. Cross-validation was performed on approximately 11,000 first-line supervisors in 79 organizations. The resulting validities were meta-analyzed across organizations, age levels, sex, and levels of education, supervisory experience, and company tenure. In all cases, validities were generalizable. Validities were also stable across time and did not appear to stem from measurement of knowledge, skills, or abilities acquired through job experience. Finally, these results provide additional evidence against the hypothesis of situational specificity of validities, the first large-sample evidence in a noncognitive domain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Using Superimposed ASK label in a 10-Gb/s multihop all-optical label swapping system

A novel optical-label-swapping technique is proposed, experimentally verified, and theoretically analyzed in this paper. The technique superimposes a low-speed amplitude-shift-keying (ASK) label on top of a high-speed dc-balanced-line-coded ASK payload. A multihop long-distance transmission experiment using a recirculating loop has been successfully demonstrated, and an experimental record is set when compared with other optical-label-swapping techniques.