Platensimycin is a selective FabF inhibitor with potent antibiotic properties

Bacterial infection remains a serious threat to human lives because of emerging resistance to existing antibiotics. Although the scientific community has avidly pursued the discovery of new antibiotics that interact with new targets, these efforts have met with limited success since the early 1960s. Here we report the discovery of platensimycin, a previously unknown class of antibiotics produced by Streptomyces platensis. Platensimycin demonstrates strong, broad-spectrum Gram-positive antibacterial activity by selectively inhibiting cellular lipid biosynthesis. We show that this anti-bacterial effect is exerted through the selective targeting of beta-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B) in the synthetic pathway of fatty acids. Direct binding assays show that platensimycin interacts specifically with the acyl-enzyme intermediate of the target protein, and X-ray crystallographic studies reveal that a specific conformational change that occurs on acylation must take place before the inhibitor can bind. Treatment with platensimycin eradicates Staphylococcus aureus infection in mice. Because of its unique mode of action, platensimycin shows no cross-resistance to other key antibiotic-resistant strains tested, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant enterococci. Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity.     

Optimization of Casting Process for Heat and Abrasion Resistant Large Gray Iron Castings

Numerical simulations were used to optimize the casting design and conditions for large cast iron castings for marine engines, Simulations of the mold filling and solidification sequences were used to analyze the problems of previous casting conditions with marked improvements for large cylinder liner parts, The amount and positions of chills were optimized to improve the mechanical properties and to minimize the shrinkage and micro porosity in the castings. Ultra sonic testing, penetration testing, and mechanical property testing show no defects in the castings with the productivity significantly increased.     

Dynamics of travelling waves in visual perception

Nonlinear wave propagation is ubiquitous in nature, appearing in chemical reaction kinetics, cardiac tissue dynamics, cortical spreading depression and slow wave sleep. The application of dynamical modelling has provided valuable insights into the mechanisms underlying such nonlinear wave phenomena in several domains. Wave propagation can also be perceived as sweeping waves of visibility that occur when the two eyes view radically different stimuli. Termed binocular rivalry, these fluctuating states of perceptual dominance and suppression are thought to provide a window into the neural dynamics that underlie conscious visual awareness. Here we introduce a technique to measure the speed of rivalry dominance waves propagating around a large, essentially one-dimensional annulus. When mapped onto visual cortex, propagation speed is independent of eccentricity. Propagation speed doubles when waves travel along continuous contours, thus demonstrating effects of collinear facilitation. A neural model with reciprocal inhibition between two layers of units provides a quantitative explanation of dominance wave propagation in terms of disinhibition. Dominance waves provide a new tool for investigating fundamental cortical dynamics.     

Strong polarization enhancement in asymmetric three-component ferroelectric superlattices

Theoretical predictions--motivated by recent advances in epitaxial engineering--indicate a wealth of complex behaviour arising in superlattices of perovskite-type metal oxides. These include the enhancement of polarization by strain and the possibility of asymmetric properties in three-component superlattices. Here we fabricate superlattices consisting of barium titanate (BaTiO3), strontium titanate (SrTiO3) and calcium titanate (CaTiO3) with atomic-scale control by high-pressure pulsed laser deposition on conducting, atomically flat strontium ruthenate (SrRuO3) layers. The strain in BaTiO3 layers is fully maintained as long as the BaTiO3 thickness does not exceed the combined thicknesses of the CaTiO3 and SrTiO3 layers. By preserving full strain and combining heterointerfacial couplings, we find an overall 50% enhancement of the superlattice global polarization with respect to similarly grown pure BaTiO3, despite the fact that half the layers in the superlattice are nominally non-ferroelectric. We further show that even superlattices containing only single-unit-cell layers of BaTiO3 in a paraelectric matrix remain ferroelectric. Our data reveal that the specific interface structure and local asymmetries play an unexpected role in the polarization enhancement.     

Identification of common microRNA-mRNA regulatory biomodules in human epithelial cancer

The complex regulatory network between microRNAs and gene expression remains an unclear domain of active research. We proposed to address in part this complex regulation with a novel approach for the genome-wide identification of biomodules derived from paired microRNA and mRNA profiles, which could reveal correlations associated with a complex network of dys-regulation in human cancer. Two published expression datasets for 68 samples with 11 distinct types of epithelial cancers and 21 samples of normal tissues were used, containing microRNA expression and gene expression profiles, respectively. As results, the microRNA expression used jointly with mRNA expression can provide better classifiers of epithelial cancers against normal epithelial tissue than either dataset alone (P=1×10^–10, F test). We identified a combination of 6 microRNA-mRNA biomodules that optimally classified epithelial cancers from normal epithelial tissue (total accuracy = 93.3%; 95% confidence intervals: 86%–97%), using penalized logistic regression (PLR) algorithm and three-fold cross-validation. Three of these biomodules are individually sufficient to cluster epithelial cancers from normal tissue using mutual information distance. The biomodules contain 10 distinct microRNAs and 98 distinct genes, including well known tumor markers such as miR-15a, miR-30e, IRAK1, TGFBR2, DUSP16, CDC25B and PDCD2. In addition, there is a significant enrichment (Fisher’s exact test P=3×10^–10) between putative microRNA-target gene pairs reported in 5 microRNA target databases and the inversely correlated microRNA-mRNA pairs in the biomodules. Further, microRNAs and genes in the biomodules were found in abstracts mentioning epithelial cancers (Fisher’s Exact test, unadjusted P<0.05). Taken together, these results strongly suggest that the discovered microRNA-mRNA biomodules correspond to regulatory mechanisms common to human epithelial cancer samples. In conclusion, we developed and evaluated a novel comprehensive method to systematically identify, on a genome scale, microRNA-mRNA expression biomodules common to distinct cancers of the same tissue. These biomodules also comprise novel microRNA and genes as well as an imputed regulatory network, which may accelerate the work of cancer biologists as large regulatory maps of cancers can be drawn efficiently for hypothesis generation.     

浅谈杂散电流的产生、危害和防治

该文通过对井下架线式电机车直流牵引网络系统中杂散电流产生原因的分析,较全面地介绍了杂散电流在井下的危害,有针对性地提出了防止杂散电流产生和扩散的有效措施,对掌握和治理杂散电流有较大的帮助。     

Creating Rhizomatic Networks and Ethics for the Marginalized Group

This paper seeks to further substantiate and appreciate the importance of West Churchman’s pragmatic philosophy, and to propose the development of what we call the participatory and rhizomatic systems approach. The aim of rhizomatics is to create a deterritoriazation of current social fields and to make sense of the creation of the rhizomatic networks and ethics for the marginalized group in practice. This paper takes the contributions of Gilles Deleuze and Felix Guattari’s notion of rhizome on ethical reasoning and incorporates them into a test. It examines how ethics for the marginalized group can assist in appreciating and developing ethical management of any systemic intervention. The paper looks into what ethics for the marginalized group is and how it is achieved in the context of rhizomatic networks.

When Social Workers Meet Special Education Teachers: Action Research to Implement Curricular Changes in Taiwanese Special Education Systems

Non-governmental organizations (NGOs) offering supported employment services in Taiwan recently have identified a missing link between their programs and the vocational programs students with disabilities received in secondary special education system. Sponsored by a national initiative aimed to enhance public education through crossover trials and social inclusion under the umbrella of ??HighScope Taiwan??, academics and mainly senior social workers devoted to supported employment for persons with intellectual disabilities started a two-way outreach program through action engagement in 2007. Action research became the common focus of the joint task forces across social work, public education systems, and academia. The article provides field-based reflections of the action research project and suggests ways in which practice of action research may increase social impact in the professional development of individuals.     

Exploration of the significance of values in the design of educational systems

In recent decades, there has been increased awareness of the need for systemic change in education. In systemic change, it is of the greatest importance that stakeholders examine and clarify their individual values and articulate shared values and state them clearly. This is necessary because values underlie visions, guide choices, decisions, and actions made in the course of design and, eventually, serve as practical tools in evaluating a system and its programs. This study explores the importance of articulating values in the design of educational systems. Given the importance of the clarification of values consented to by stakeholders and the lack of previous in-depth studies, the paper concludes that it is urgent to develop systemic and comprehensive value categories to aid in articulating core values and to serve as guidelines for applying these values in educational systems design.