Epigenetic Targets for Oligonucleotide Therapies of Pulmonary Arterial Hypertension

Arterial wall remodeling underlies increased pulmonary vascular resistance and right heart failure in pulmonary arterial hypertension (PAH). None of the established vasodilator drug therapies for PAH prevents or reverse established arterial wall thickening, stiffening, and hypercontractility. Therefore, new approaches are needed to achieve long-acting prevention and reversal of occlusive pulmonary vascular remodeling. Several promising new drug classes are emerging from a better understanding of pulmonary vascular gene expression programs. In this review, potential epigenetic targets for small molecules and oligonucleotides will be described. Most are in preclinical studies aimed at modifying the growth of vascular wall cells in vitro or normalizing vascular remodeling in PAH animal models. Initial success with lung-directed delivery of oligonucleotides targeting microRNAs suggests other epigenetic mechanisms might also be suitable drug targets. Those targets include DNA methylation, proteins of the chromatin remodeling machinery, and long noncoding RNAs, all of which act as epigenetic regulators of vascular wall structure and function. The progress in testing small molecules and oligonucleotide-based drugs in PAH models is summarized.     

Sanitary legislation governing Food Services in Brazil

The Technical Regulation of Good Practices for Brazilian Food Services (Regulamento Técnico de Boas Práticas para Serviços de Alimentação do Brasil) can be complemented by sanitary surveillance agencies at the state, district and municipal levels by tailoring it to location-specific requirements. The purpose of the present study was to survey sanitary legislation governing Brazilian Food Services. During the period from November 2011 to November 2012, a survey was conducted with the sanitary surveillance agencies from the various states, capitals and the Federal District. A previously prepared and tested tool was used for data collection, comprising 10 questions. Only 10 (19.2%) of the sanitary codes had been established prior to RDC Resolution n° 216/2004 and were not complementary. Of the legislation cited as complementary, only the states of Santa Catarina, Rio Grande do Sul and São Paulo and the capital of the state of São Paulo truly presented additional and location-specific aspects. No legislation that was specific to hospital kitchens was found. The majority of participating coordination, including the Evaluation List for Good Practices in Food Services, was also verified; however, it had not been published. In conclusion, a gap in sanitary surveillance services exists, which was caused by the lack of location-specific food service regulations.     

Understanding value creation in closed loop supply chains – Past findings and future directions

The topic of value creation through the recovery of returned products in closed loop supply chains is scattered across various bodies of literature. We undertake a systematic literature review of 144 articles in relevant green, reverse and closed loop supply chain literature to synchronize existing knowledge on value creation. Value manifestations of four types of value, namely economic, environmental, information and customer value, are identified. Value adding concepts from the forward- and reverse supply chain may leverage the process of value creation. They are classified into six subclasses, namely partnerships and collaboration, product design characteristics, service concepts, IT solutions, supply chain processes and organizational characteristics. We present a conceptual framework on a strategic level. In this way companies can create competitive advantages by closing the loop. The results of the literature analysis suggest avenues for future research on the operational and strategic level.     

Multiplex PCR system to track authorized and unauthorized genetically modified soybean events in food and feed

A diverse range of genetic elements has been used to develop genetically modified organisms (GMOs) over the last 18 years. Screening methods that target few elements, such as the Cauliflower Mosaic Virus 35S promoter (P-35S) and Agrobacterium tumefaciens nopaline terminator (T-nos), are not sufficient to screen GMOs. In the present study, a multiplex PCR system for all globally commercialized GM soybean events was developed to easily trace the events. For this purpose, screening elements of 24 GM soybean events were investigated and 9 screening targets were selected and divided into three individual triplex PCR systems: P-35S, ribulose-1,5-bisphosphate carboxylase small subunit promoter of Arabidopsis thaliana, T-nos, T-35S, pea E9 terminator, open reading frame 23 terminator of A. tumefaciens, proteinase inhibitor II terminator of potato, acetohydroxy acid synthase large subunit terminator of A. thaliana, and the revealed 3′ flanking sequences of DP-305423-1. The specificity of the assays was confirmed using thirteen GM soybean events as the respective positive/negative controls. The limit of detection of each multiplex set, as determined using certified reference materials of specific GM events, ranged from 0.03 to 0.5%, depending upon target. Furthermore, 26 food samples that contained soybean ingredients, which were purchased from the USA, China, Japan, and Korea, were analyzed, 17 of which contained one or more GM soybean events. These results suggest that the developed screening method can be used to efficiently track and identify 24 GM soybean events in food and feed.     

Assessing trophic position quantification methods for three piscivorous freshwater fish using stable isotopes and stomach contents

Accurate trophic position (TP) estimates are important for the development of ecosystem-based management plans. TPs can be quantified by carbon (δ¹³C) and nitrogen (δ¹⁵N) stable isotopes in tissues, but these can disagree with observed and perceived feeding ecology. A recent method that has used a scaled diet-tissue discrimination factor (DTDF), reflecting the inverse relationship between DTDF and δ¹⁵N, was found to better describe TPs of predatory fish species in marine ecosystems, but this has not been tested in freshwater ecosystems. Here, we compare methods of TP estimations in the Lake Huron-Erie corridor (HEC), a system where high diversity of prey items has contributed to the concern that foraging ecology of piscivorous fish species is poorly understood. Using δ¹⁵N and δ¹³C, we quantified TP of longnose gar (Lepisosteus osseus), largemouth bass (Micropterus salmoides), and northern pike (Esox lucius) to assess the efficacy of a scaled DTDF compared to traditional DTDF isotope methods and stomach content analysis (SCA). The scaled DTDF method produced TP estimates that were at times consistent with SCA and were generally higher and with a greater range among individuals than non-scaled DTDFs. The scaled method was not sensitive to baseline choice nor influenced by incorporating carbon source in the model. Greater variability of TP estimates using a scaled DTDF suggests more complex trophic structuring in the upper trophic level guild of the HEC. These results, particularly the lack of baseline sensitivity, provide support for using the scaled DTDF in freshwater food web characterization.     

Dynamic Stabilization of DNA Assembly by Using Pyrrole-Imidazole Polyamide

We used N-methylpyrrole (Py)-N-methylimidazole-(Im) polyamide as an exogenous agent to modulate the formation of DNA assemblies at specific double-stranded sequences. The concept was demonstrated on the hybridization chain reaction that forms linear DNA. Through a series of melting curve analyses, we demonstrated that the binding of Py−Im polyamide positively influenced both the HCR initiation and elongation steps. In particular, Py−Im polyamide was found to drastically stabilize the DNA duplex such that its thermal stability approached that of an equivalent hairpin structure. Also, the polyamide served as an anchor between hairpin pairs in the HCR assembly, thus improving the originally weak interstrand stability. We hope that these proof-of-concept results can inspire future use of Py−Im polyamide as a molecular tool to modulate the formation of DNA assemblies.     

对荷载规范中旋转壳顶的风载体型系数的研究

采用CFD数值模拟方法,研究了旋转壳顶在不同矢跨比、长宽比等参数影响下的风压分布特性,并得到风载体型系数,对现行风荷载规范作了一定的补充。     

Zk线性码的对称形式的MacWilliams恒等式

该文定义了Zk线性码的码字的对称重量计数公式，利用离散的Hadamard变换，建立了线性码与其对偶码之间的对称形式的MacWilliams恒等式．     

Multiple Scan Chain Design for Two-Pattern Testing

Non-standard fault models often require the application of two-pattern testing. A fully-automated approach for generating a multiple scan chain-based architecture is presented so that two-pattern test sets generated for the combinational core can be applied to the sequential circuit. Test time and area overhead constraints are considered.