Characterisation of flucloxacillin and 5-hydroxymethyl flucloxacillin haptenated HSA in vitro and in vivo

Flucloxacillin is a synthetic penicillin used in the treatment of Staphylococcal infections. Adverse reactions to the drug are believed to arise through covalent modification of proteins, with tissue damage occurring secondary to an immune reaction. Serum proteins have been shown by adduct-specific antibodies to be modified by flucloxacillin, but the nature and sites of modification have not been characterised. Here, in vitro studies on HSA have shown by MS that the modification of protein lysine residues occurs in a dose-, time- and site-dependent manner. Affinity, cation exchange and reversed phase chromatography prior to MS revealed in vivo modification of HSA with flucloxacillin in tolerant patients, with up to nine modified lysine residues being detected in each patient, and with modification of Lys190 and Lys212 being detected in 8/8 patients. It was also revealed for the first time that plasma proteins could be modified with the 5-hydroxymethyl metabolite of flucloxacillin, and that essentially the same Lys residues were targeted by both the parent drug and its metabolite. This study provides a detailed characterisation of sites of chemical modification of an endogenous target and reveals candidate peptides for T-cell and antibody assays of flucloxacillin hypersensitivity.     

Mediating Power: Distance Learning Interfaces, Classroom Epistemology, and the Gaze

Distance learning's interfaces—from corresponding through the postal service to the televised talking head—have traditionally been designed from the top down, supporting banking models of learning or, in writing instruction, current-traditional rhetoric pedagogies. Due to temporal and spatial constraints, these interface designs often support (or encourage) one-way communication from the instructor to the student. Students mostly interact with the instructor by asking questions or submitting work, and they tend to have little correspondence with other peers. These methods clearly privilege the instructor's knowledge and evaluation. Furthermore, these interface designs empower the instructor to gaze upon the students and assess them—often not as a corporeal body but as a corpus of texts. Thus, each interface adopted for distance learning sets up a power dynamic in which the capability to share the roles of creating knowledge is juxtaposed with the instructor's capability to normalize the students and reify their own authority through their gaze. In this article we examine the traditional classroom interface through the correspondence course interface, the simulated classroom interface, and the synchronous video interface to raise questions about the infrastructures of distance learning and their implications for student learning.     

灵活高效的模块化系统

更换整机上模块的能力,可以在保证系统整体功能不变的基础上增减部分功能,以节约成本。随着半导体产业成本不断上涨,竞争日趋激烈,生产商们在保证产量最大化的同时,也绞尽脑汁提高产品质量。因此,他们需要灵活的设备以满足其快速升级和降低成本的要求。提高产出通常以每单元小     

Energy Efficient Hardware Loop Based Optimization for CGRAs

Journal of Signal Processing Systems - Research interest and industry investment in edge computing solutions have increased dramatically in recent years. Consequent quest for balanced performance,...     

Legal information retrieval for understanding statutory terms

In this work we study, design, and evaluate computational methods to support interpretation of statutory terms. We propose a novel task of discovering sentences for argumentation about the meaning of statutory terms. The task models the analysis of past treatment of statutory terms, an exercise lawyers routinely perform using a combination of manual and computational approaches. We treat the discovery of sentences as a special case of ad hoc document retrieval. The specifics include retrieval of short texts (sentences), specialized document types (legal case texts), and, above all, the unique definition of document relevance provided in detailed annotation guidelines. To support our experiments we assembled a data set comprising 42 queries (26,959 sentences) which we plan to release to the public in the near future in order to support further research. Most importantly, we investigate the feasibility of developing a system that responds to a query with a list of sentences that mention the term in a way that is useful for understanding and elaborating its meaning. This is accomplished by a systematic assessment of different features that model the sentences’ usefulness for interpretation. We combine features into a compound measure that accounts for multiple aspects. The definition of the task, the assembly of the data set, and the detailed task analysis provide a solid foundation for employing a learning-to-rank approach.

     

Amplification‐Free Multi‐RNA‐Type Profiling for Cancer Risk Stratification via Alternating Current Electrohydrodynamic Nanomixing

Simultaneous analysis of messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA)—multi‐RNA‐type profiling—is increasingly crucial in cancer diagnostics. Yet, rapid multi‐RNA‐type profiling is challenging due to enzymatic amplification reliance and RNA‐type‐dependent characteristics. Here, a nanodevice is reported to uniquely use alterable alternating current electrohydrodynamic (ac‐EHD) forces to enhance probe–target hybridization prior to direct native RNA target detection, without target amplification or surface functionalization. To exemplify clinical applicability, noninvasive screening of next‐generation prostate cancer (PCa) RNA biomarkers (of different types) in patient urine samples is performed. A strong correlation between multi‐RNA‐type expression and aggressive PCa is found, and the nanodevice performance is statistically evaluated. It is believed that this miniaturized system exhibits great potential for cancer risk stratification via multi‐RNA‐type profiling.     

Developments in quantitative dimensional synthesis (1970-present): four-bar motion generation

Dimensional synthesis is a type of inverse problem in linkage kinematics where the objective is to calculate the linkage dimensions required to achieve prescribed linkage output motion. Motion generation is a particular category of dimensional synthesis where the objective is to calculate the linkage dimensions required to achieve a group of prescribed link positions. In motion generation for a four-bar linkage, positions are prescribed for the coupler link. While early motion generation methods were primarily qualitative, ongoing advancements in computing hardware and software continue to make quantitative motion generation more practical. By providing overviews of works representative of developments in quantitative four-bar motion generation since 1970, this work is essentially an overview that spans over 40 years of developments in quantitative four-bar motion generation.     

Adaptive autonomous underwater vehicles for littoral surveillance

Autonomous underwater vehicles (AUVs) have gained more interest in recent years for military as well as civilian applications. One potential application of AUVs is for the purpose of undersea surveillance. As research into undersea surveillance using AUVs progresses, issues arise as to how an AUV acquires, acts on, and shares information about the undersea battle space. These issues naturally touch on aspects of vehicle autonomy and underwater communications, and need to be resolved through a spiral development process that includes at sea experimentation. This paper presents a recent AUV implementation for active anti-submarine warfare tested at sea in the summer of 2010. On-board signal processing capabilities and an adaptive behavior are discussed in both a simulation and experimental context. The implications for underwater surveillance using AUVs are discussed.