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Under cyclic load, local fatigue damage will occur in the metal damper widely used in the shear wall. This will deteriorate the stiffness of damper and weaken the hysteresis behaviour. The present paper proposed a new and easy method to manufacture kinds of coupling beam dampers. A thermography-based experiment was used to study the energy dissipation and damage accumulation during fatigue process of the metal damper. Based on the temperature variation related to fatigue damage process, the relationship between the plastic deformation and thermal energy dissipation was quantitatively established. Besides, the relationships between the temperature increase to damage accumulation and mechanical load were analyzed systematically. [ABSTRACT FROM AUTHOR]

By the field experiment, we set up the treatments of non-application of potash fertilizer, conventional fertilization, balanced fertilization and halved application of potash fertilizer, and studied the rffect of different treatments on rice yield and soil nutrient content. The results showed that compared with non-application of potash fertilizer, conventional fertilization and balanced fertilization significantly increased the spike length, thousand kernel weight, yield and total potassium content of the stalk, as well as soil organic matter, total nitrogen and avalable phosphorus content; compared with conventional fertilization, the balanced fertilization did not significantly increase the rice growth and yield, but effectively increased rice grain total nitrogen, stalk total nitrogen and total phosphorus content, a well as soil available phosphorus and available potassium content. It could be found that potash fertilizer played a certain role in increaing rice yield and soil nutrient content, and the balanced fertilization had the most significant efect. [ABSTRACT FROM AUTHOR]

Male infertility is considered a common health problem, and non-obstructive azoospermia with unclear pathogenesis is one of the most challenging tasks for clinicians. The objective of this study was to investigate the differential serum metabolic pattern in non-obstructive azoospermic men and to determine potential biomarkers related to spermatogenic dysfunction. Serum samples from patients with non-obstructive azoospermia (n = 22) and healthy controls (n = 31) were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Serum metabolomic profiling could differentiate non-obstructive azoospermic patients from healthy control subjects. A total of 24 metabolites were screened and identified as potential markers, many of which are involved in energy production, oxidative stress and cell apoptosis in spermatogenesis. Moreover, the results showed that various metabolic pathways, including D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, pyruvate metabolism, the citrate cycle and alanine, aspartate and glutamate metabolism, were disrupted in patients with non-obstructive azoospermia. Our results indicated that the serum metabolic disorders may contribute to the etiology of non-obstructive azoospermia. This study suggested that serum metabolomics could identify unique metabolic patterns of non-obstructive azoospermia and provide novel insights into the pathogenesis underlying male infertility. [ABSTRACT FROM AUTHOR]

We present a new Retarding Potential Analyzer (RPA) design that is capable of measuring keVlevel energy, high-density plasma beams. This instrument overcomes the limitations of existing RPAs and can operate in plasmas with densities in excess of 1 × 1015 m-3 and ion energies up to 1200 eV. The RPA design parameters were determined by analyzing the electron density and temperature, the sheath thickness, and the ion density in the beam based on the Faraday probe and Langmuir probe measurements. A previously unobserved grid spacing arcing phenomenon was observed in experiments. This arcing phenomenon was also investigated and a grid spacing criterion was proposed to eliminate the arcing. We present measurement results on the plasma beam emitted from the 20 cm Xenon ion thruster used on the Chinese SJ-9A satellite. [ABSTRACT FROM AUTHOR]

Because grazing-incidence Kirkpatrick-Baez (KB) microscopes have better resolution and collection efficiency than pinhole cameras, they have been widely used for x-ray imaging diagnostics of laser inertial confinement fusion. The assembly and adjustment of a multichannel KB microscope must meet stringent requirements for image resolution and reproducible alignment. In the present study, an eight-channel KB microscope was developed for diagnostics by imaging self-emission x-rays with a framing camera at the Shenguang-II Update (SGII-Update) laser facility. A consistent object field of view is ensured in the eight channels using an assembly method based on conical reference cones, which also allow the intervals between the eight images to be tuned to couple with the microstrips of the x-ray framing camera. The eight-channel KB microscope was adjusted via real-time x-ray imaging experiments in the laboratory. This paper describes the details of the eight-channel KB microscope, its optical and multilayer design, the assembly and alignment methods, and results of imaging in the laboratory and at the SGII-Update. [ABSTRACT FROM AUTHOR]

Disaster management with respect to urban structures has received more attention in recent years. In disaster management, the most vulnerable structures in a modern society are the critical networks, such as transportation networks. The vulnerability analysis of spatial networks should not depend only on the topological structure; some non-topological attributes, such as population information, should also be considered. In a rescue operation, decision-making problems are very often uncertain or vague because of the lack of information. Therefore, the classification of a high or low-risk area on the basis of spatial information should not have crisp boundaries and it would be more reasonable to use a fuzzy approach. In this paper, population information and a betweenness centrality measure of the road network were used as the evaluation criteria, and a fuzzy multiple-attribute decision-making (MADM) approach was used to support a vulnerability analysis of the road network of Finland for disaster management. In order to validate the model, results were compared with original population information and a betweenness attribute map. The validation results showed the hotspots in a fuzzy MADM vulnerability map have a similar pattern to an original input attributes map and the number of hotspots were reduced to a reasonable scale in order to improve rescue efficiency. [ABSTRACT FROM AUTHOR]

The regulation of entry into and progression through mitosis is important for cell proliferation. Polo-like kinase 1 (PLK1) is involved in multiple stages of mitosis. Forkhead box protein M1 (FOXM1) has multiple functions in tumori-genesis and, in elevated levels, is frequently associated with cancer progression. The present study reports that FOXM1, a substrate of PLK1, controls the transcription mechanism that mediates the PLK1- dependent regulation of the cell cycle. The present study investigated the expression of PLK1 and FOXM1 in the clear renal cell carcinoma 769-P and ACHN cell lines, and indicated that the expression of PLK1 and FOXM1 are correlated in human renal cell cancer cell lines and that the suppression of PLK1 may decrease the expression of FOXM1. The knockdown of FOXM1 or PLK1 in renal cell cancer cell lines caused cell cycle progression to be blocked. As a result, the present study indicated the involvement of FOXM1 in PLK1-regulated cell cycle progression. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the interleukin (IL) 1β, IL-6 and prostaglandin E2 (PGE2) concentrations in aqueous humour in patients undergoing femtosecond laser-assisted cataract surgery. Methods In 27 eyes of 27 patients undergoing femtosecond laser-assisted cataract surgery (femto group), aqueous humour of 100 μL was collected after laser treatment. In 15 eyes of 15 subjects undergoing routine cataract surgery (control group), aqueous humour of 100 μL was also collected. The IL-1β, IL-6 and Prostaglandin E2 (Human Interleukin 1β, Interleukin 6 and Prostaglandin E2 ELISA Kits, Bio-Swamp Life Science) were used to determine the concentrations of IL-1β, IL-6 and PGE2 in the aqueous humour. All patients were treated with non-steroidal anti-inflammatory drugs prior to surgery. Results For IL-1β, IL-6 and PGE2, respectively, the mean concentration values in aqueous humour were 25.6, 24.6 and 64.2 pg/mL in the femto group, and 17.1, 15.2 and 45.7 pg/mL in the control group (table 2). Concentrations of IL-1β, IL-6 and PGE2 were significantly higher in the femto group than those in the control group (all p<0.01). There were no significant correlations between concentrations of IL-1β, IL-6 or PGE2 and age, cataract densities, suction time or laser time (all p>0.05). Conclusions Inflammatory cytokines IL-1β, IL-6 and PGE2 significantly increased after femtosecond laser-assisted cataract surgery, which maybe the cause of intraoperative miosis seen in these patients. [ABSTRACT FROM AUTHOR]

Background: The autoimmune disease systemic lupus erythematosus (SLE) has a modified epigenome with modified tri-methylation of histone H3 lysine 4 (H3K4me3) at specific loci across the genome. H3K4me3 is a canonical chromatin mark of active transcription. Recent studies have suggested that H3K4me3 breadth has an important regulatory role in cell identity. This project examined H3K4me3 breadth at transcription start sites (TSS) in primary monocytes and its association with differential gene transcription in SLE. Results: Integrative analysis was applied to chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) data generated from primary monocytes as well as genomic data available in public repositories. Four distinctive H3K4me3 patterns of ChIP-seq peaks were identified at 8399 TSSs. Narrow peaks were highly enriched with genes related to housekeeping functions. The broader peaks with extended H3K4me3 immediately upstream and/or downstream of TSS were associated with immune response genes. Many TSSs had downstream H3K4me3 extended to ~650 bp, where the transition of H3K4me3 to H3K36me3, a transcriptional elongation mark, is often found. The H3K4me3 pattern was strongly associated with transcription in SLE. Genes with narrow peaks were less likely (OR = 0.14, p =2x10-4) while genes with extended downstream H3K4me3 were more likely (OR = 2.37, p =1x10-11) to be overexpressed in SLE. Of the genes significantly overexpressed in SLE, 78.8 % had increased downstream H3K4me3 while only 47.1 % had increased upstream H3K4me3. Gene transcription sensitively and consistently responded to H3K4me3 change downstream of TSSs. Every 1 % increase of H3K4me3 in this region leads to ~1.5 % average increase of transcription. Conclusions: We identified the immediate TSS downstream nucleosome as a crucial regulator responsible for transcription changes in SLE. This study applied a unique method to study the effect of H3K4me3 breadth on diseases and revealed new insights about epigenetic modifications in SLE, which could lead to novel treatments. [ABSTRACT FROM AUTHOR]

While most cancer types are resistant to mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin, recent studies have identified mTORC2 as an important prospective therapeutic target for cancer. The present study assessed the effects of mTORC2 inhibitor PP242 on the proliferation and migration of bladder cancer cells by using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine incorporation, wound healing and Transwell assays. Furthermore, the phosphorylation status of downstream signaling proteins of mTORC1 and mTORC2 was assessed using western blot analysis. The results demonstrated that PP242 concentration-dependently inhibited the proliferation of bladder cancer cells. Simultaneously, the migration ability of bladder cancer cells was suppressed by PP242. In addition, PP242 markedly restrained the phosphorylation of AKT1 and mTORC2, while the phosphorylation status of S6K1 and mTORC1 was not affected. These results suggested that PP242 exerts potent inhibitory effects on bladder cancer cells by modulating the activity of the mTORC2/AKT1 pathway. [ABSTRACT FROM AUTHOR]

The growing importance of protein aggregation diseases requires the development of new methods to elucidate the molecular features that are responsible for the incipient protein--protein interactions. Kinetic information from protein--protein association/dissociation reactions is particularly valuable for revealing mechanistic insight, but robust tools that can provide this information are somewhat lacking. In this work, we describe a hydrogen/deuterium exchange (HDX)-based method that provides rate constant information for protein oligomer dissociation, using the well-studied β-lactoglobulin (βLG) dimer as a model system to validate our approach. By measuring the rate of exchange at different regions of the protein using top-down tandem mass spectrometry and fitting the resulting data to an appropriate mathematical model, we are able to extract the dimer's dissociation rate constant. We exploit the fact that regions of the protein that are part of the protein--protein interface have exchange patterns that are distinct from noninterfacial regions. Tins observation indicates that the HDX/MS method not only provides kinetic information but also could provide structural insight about the interface at the same time, which would be very valuable for previously uncharacterized protein--protein complexes. Analytical Chemistry animals, even if sample analysis for the animal and human samples was done at times up to a year apart. [ABSTRACT FROM AUTHOR]

The dynamics of water in polyethylene oxide (PEO)/LiCl solution has been studied with quasielastic neutron scattering experiments and molecular dynamics (MD) simulations. Two different time scales of water diffusion representing interfacial water and bulk water dynamics have been identified. The measured diffusion coefficient of interfacial water remained 5-10 times smaller than that of bulk water, but both were slowed by approximately 50% in the presence of Li+. Detailed analysis of MD trajectories suggests that Li+ is favorably found at the surface of the hydration layer, and the probability to find the caged Li+ configuration formed by the PEO is lower than for the noncaged Li+-PEO configuration. In both configurations, however, the slowing down of water molecules is driven by reorienting water molecules and creating water-Li+ hydration complexes. Performing the MD simulation with different ions (Na+ and K+) revealed that smaller ionic radius of the ions is a key factor in disrupting the formation of PEO cages by allowing spaces for water molecules to come in between the ion and PEO. [ABSTRACT FROM AUTHOR]

Bone morphogenetic proteins (BMPs) play important roles in skeletal development and repair. Previously, we found fibroblast growth factor 2 (FGF2) induced up-regulation of BMP2, 3, 4 in the process of rabbit articular cartilage repair, which resulted in satisfactory repair effects. As BMP2/4 show a clearly positive effect for cartilage repair, we investigated the functions of BMP3 in rabbit articular cartilage repair. In this paper, we find that BMP3 inhibits the repair of partial-thickness defect of articular cartilage in rabbit by inducing the degradation of extracellular matrix, interfering with the survival of chondrocytes surrounding the defect, and directly inhibiting the expression of BMP2 and BMP4. Meanwhile BMP3 suppress the repair of full-thickness cartilage defect by destroying the subchondral bone through modulating the proliferation and differentiation of bone marrow stem cells (BMSCs), and directly increasing the expression of BMP4. Although BMP3 has different functions in the repair of partial and full-thickness defects of articular cartilage in rabbit, the regulation of BMP expression is involved in both of them. Together with our previous findings, we suggest the regulation of the BMP signaling pathway by BMP3 is essential in articular cartilage repair. [ABSTRACT FROM AUTHOR]

Gastric diverticulum (GD) is a pouch protruding from the gastric wall. It is rare and in the majority of cases, asymptomatic. Usually GDs are detected incidentally by gastrointestinal study. The current study reports one case and a literature review of GD mimicking an adrenal mass. A 49-year-old male presented with a low-density lesion in the left adrenal area, but no symptoms of an adrenal adenoma. The lesion was identified as a gastric diverticulum in the fundus of the stomach following enhancement of computed tomography (CT) imaging using an oral contrast agent. Although the majority of previously reported cases utilized upper gastrointestinal barium studies to confirm the presence of GD, the current study demonstrated that CT scanning enhanced with oral contrast material may aid in the differentiation of adrenal masses from other gastrointestinal abnormalities. [ABSTRACT FROM AUTHOR]

During non-severe fault conditions, crowbar protection is not activated and the rotor windings of a doubly-fed induction generator (DFIG) are excited by the AC/DC/AC converter. Meanwhile, under asymmetrical fault conditions, the electrical variables oscillate at twice the grid frequency in synchronous dq frame. In the engineering practice, notch filters are usually used to extract the positive and negative sequence components. In these cases, the dynamic response of a rotor-side converter (RSC) and the notch filters have a large influence on the fault current characteristics of the DFIG. In this paper, the influence of the notch filters on the proportional integral (PI) parameters is discussed and the simplified calculation models of the rotor current are established. Then, the dynamic performance of the stator flux linkage under asymmetrical fault conditions is also analyzed. Based on this, the fault characteristics of the stator current under asymmetrical fault conditions are studied and the corresponding analytical expressions of the stator fault current are obtained. Finally, digital simulation results validate the analytical results. The research results are helpful to meet the requirements of a practical short-circuit calculation and the construction of a relaying protection system for the power grid with penetration of DFIGs. [ABSTRACT FROM AUTHOR]

Background: For membrane protein production, the Escherichia coli T7 RNA polymerase (T7 RNAP)-based protein production strain BL21(DE3) in combination with T7-promoter based expression vectors is widely used. Cells are routinely cultured in Lysogeny broth (LB medium) and expression of the chromosomally localized t7rnap gene is governed by the isopropyl-β-d-1-thiogalactopyranoside (IPTG) inducible lacUV5 promoter. The T7 RNAP drives the expression of the plasmid borne gene encoding the recombinant membrane protein. Production of membrane proteins in the cytoplasmic membrane rather than in inclusion bodies in a misfolded state is usually preferred, but often hampered due to saturation of the capacity of the Sec-translocon, resulting in low yields. Results: Contrary to expectation we observed that omission of IPTG from BL21(DE3) cells cultured in LB medium can lead to significantly higher membrane protein production yields than when IPTG is added. In the complete absence of IPTG cultures stably produce membrane proteins in the cytoplasmic membrane, whereas upon the addition of IPTG membrane proteins aggregate in the cytoplasm and non-producing clones are selected for. Furthermore, in the absence of IPTG, membrane proteins are produced at a lower rate than in the presence of IPTG. These observations indicate that in the absence of IPTG the Sec-translocon capacity is not/hardly saturated, leading to enhanced membrane protein production yields in the cytoplasmic membrane. Importantly, for more than half of the targets tested the yields obtained using un-induced BL21(DE3) cells were higher than the yields obtained in the widely used membrane protein production strains C41(DE3) and C43(DE3). Since most secretory proteins reach the periplasm via the Sec-translocon, we also monitored the production of three secretory recombinant proteins in the periplasm of BL21(DE3) cells in the presence and absence of IPTG. For all three targets tested omitting IPTG led to the highest production levels in the periplasm. Conclusions: Omission of IPTG from BL21(DE3) cells cultured in LB medium provides a very cost- and time effective alternative for the production of membrane and secretory proteins. Therefore, we recommend that this condition is incorporated in membrane- and secretory protein production screens. [ABSTRACT FROM AUTHOR]

Starting from the classical dynamic model of salientpole permanent-magnet synchronous machines (PMSMs) expressed in the stationary reference frame, this paper presents a mathematical model reconstruction process for salient-pole PMSMs, from which an extended flux-based machine model is derived. Compared with the commonly used extended electromotive force-based model, the extended flux-based model has notable advantages of simpler model structure and less sensitive to the variations of machine parameters and operating conditions. A new extended flux model-based rotor position estimator is then proposed for sensorless control of salient-pole PMSMs by utilizing a sliding-mode observer with a dynamic position compensator. The latter improves the dynamic performance and low-speed operating capability of the sensorless control system. Both simulation and experimental results are provided to validate the proposed rotor position estimator and the sensorless control system for salient-pole PMSMs. [ABSTRACT FROM AUTHOR]

Chromatin remodeling processes can drive acinar cell fate decisions. [ABSTRACT FROM AUTHOR]

Background: Tetrandrine is a natural chemical product purified from fourstamen stephania root which recently has been shown to act similarly as synthesized drug efflux pump inhibitor verapamil. The aim of the study is to examine whether tetrandrine could potentiate anti-tubercular drugs to which Mycobacterium tuberculosis (MTB) has turned resistant via efflux mechanisms. Methods: We screened 200 MTB clinical isolates using drug sensitivity test to look for those who have turned resistant to the drugs most probably due to efflux mechanisms. We found 29 isoniazid (INH) and ethambutol (EMB) - dual resistant (IEDR) strains. Then we tested if treatment with tetrandrine or verapamil could reverse drug resistance to INH and/or EMB in IEDR isolates. Results: There is a parallel resistance among EMB- and INH-resistant strains in the tested clinical isolates. Among INH-resistant strains, 65% was also EMB-resistant. This suggests an involvement of efflux mechanisms which can lead to dual drug resistance in IEDR clinical isolates. Similar to a synthesized efflux pump inhibitor verapamil, tetrandrine treatment together with INH or EMB brought down the MICs from the clinical level of drug resistance to the sensitive range of both drugs. The effective rate reached 82% among IEDR clinical isolates. Conclusions: Combinational application of tetrandrine with INH or EMB increased drug efficacy. Drugs like tetrandrine may help to reduce drug dosage thus alleviate side effects. [ABSTRACT FROM AUTHOR]

Periostin, a secreted extracellular matrix protein, is highly expressed in wound healing and in various types of human cancer and is involved in angiogenesis. Keloids, considered dermal benign tumors, are granulomatous lesions characterized by capillary proliferation. However, the underlying regulatory mechanism of angiogenesis in keloids remains to be elucidated. The present study aimed to examine the effect of periostin on angiogenesis in keloids. The expression of periostin was upregulated and the vessel density was higher in human keloids compared with normal tissue, observed following staining with CD31 and CD105. Periostin demonstrated a markedly positive correlation with blood vessel density, which was assessed using CD31 staining (r=0.711; P<0.01) and a weak correlation was observed using CD105 staining (r=0.251; P<0.01). Conditioned medium from keloid fibroblasts (KFs) promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs) compared with normal fibroblasts and this effect may have been abrogated by the short hairpin RNA knockdown of periostin. Treatment with recombinant human periostin promoted the migration and tube formation of HUVECs by activating the extracellular signal-regulated kinase 1/2 and focal adhesion kinase signaling pathway. In addition, periostin increased the secretion of vascular endothelial growth factor and angiopoietin-1 in the KFs. In conclusion, these data suggested that upregulation in the level of periostin may promote angiogenesis directly and indirectly in keloids and may be a key factor in keloid development. Periostin may, therefore, be a promising therapeutic target in the treatment of keloids and other angioproliferative diseases. [ABSTRACT FROM AUTHOR]

Background: Population-wide genotypic and phenotypic data is frequently used to predict the disease risk or genetic/phenotypic values, or to localize genetic variations responsible for complex traits. GPOPSIM is a simulation tool for pedigree, phenotypes, and genomic data, with a variety of population and genome structures and trait genetic architectures. It provides flexible parameter settings for a wide discipline of users, especially can simulate multiple genetically correlated traits with desired genetic parameters and underlying genetic architectures. Results: The model implemented in GPOPSIM is presented, and the code has been made freely available to the community. Data simulated by GPOPSIM is a good mimic to the real data in terms of genome structure and trait underlying genetic architecture. Conclusions: GPOPSIM would be a useful tool for the methodological and theoretical studies in the population and quantitative genetics and breeding. [ABSTRACT FROM AUTHOR]

We recently showed that progesterone treatment abolished arrhythmias and sudden cardiac death in a transgenic rabbit model of long QT syndrome type 2 (LQT2). Moreover, levels of cardiac sarco(endo) plasmic reticulum Ca2+-ATPase type 2a (SERCA2a) were upregulated in LQT2 heart extracts. We hypothesized that progesterone treatment upregulated SERCA2a expression, thereby reducing Ca2+-dependent arrhythmias in LQT2 rabbits. We therefore investigated the effect of progesterone on SERCA2a regulation in isolated cardiomyocytes. Cardiomyocytes from neonatal (3- to 5-day-old) rabbits were isolated, cultured, and treated with progesterone and other pharmacological agents. Immunoblotting was performed on total cell lysates and sarcoplasmic reticulum-enriched membrane fractions for protein abundance, and mRNA transcripts were quantified using real-time PCR. The effect of progesterone on baseline Ca2+ transients and Ca2+ clearance was determined using digital imaging. Progesterone treatment increased the total pool of SERCA2a protein by slowing its degradation. Using various pharmacological inhibitors of degradation pathways, we showed that progesterone-associated degradation of SERCA2a involves ubiquitination, and progesterone significantly decreases the levels of ubiquitin-tagged SERCA2a polypeptides. Our digital imaging data revealed that progesterone significantly shortened the decay and duration of Ca2+ transients. Progesterone treatment increases protein levels and activity of SERCA2a. Progesterone stabilizes SERCA2a, in part, by decreasing the ubiquitination level of SERCA2a polypeptides. [ABSTRACT FROM AUTHOR]

Prostate cancer is thought to be driven by oxidative stress, lipid metabolism, androgen receptor (AR) signaling, and activation of the PI3K--AKT--mTOR pathway, but it is uncertain how they may become coordinated during progression to castration-resistant disease that remains incurable. The mitotic kinase polo-like kinase 1 (Plk1) is elevated in prostate cancer, where its expression is linked to tumor grade. Notably, Plk1 signaling and lipid metabolism were identified recently as two of the top five most upregulated pathways in a mouse xenograft model of human prostate cancer. Herein, we show that oxidative stress activates both the PI3K--AKT--mTOR pathway and AR signaling in a Plk1-dependent manner in prostate cells. Inhibition of the PI3K--AKT--mTOR pathway prevented oxidative stress-induced activation of AR signaling. Plk1 modulation also affected cholesteryl ester accumulation in prostate cancer via the SREBP pathway. Finally, Plk1 inhibition enhanced cellular responses to androgen signaling inhibitors (ASI) and overcame ASI resistance in both cultured prostate cancer cells and patient-derived tumor xenografts. Given that activation of AR signaling and the PI3K--AKT--mTOR pathway is sufficient to elevate SREBP-dependent expression of key lipid biosynthesis enzymes in castration-resistant prostate cancer (CRPC), our findings argued that Plk1 activation was responsible for coordinating and driving these processes to promote and sustain the development of this advanced stage of disease. Overall, our results offer a strong mechanistic rationale to evaluate Plk1 inhibitors in combination drug trials to enhance the efficacy of ASIs in CRPC. [ABSTRACT FROM AUTHOR]

In this article, a new way of preparing starch-based nanoparticles (SNPs) with high yields by a polyoxometalates acid treatment is presented. The particle morphology, mean size and size distribution of the obtained SNPs are characterized using a dynamic light scattering (DLS) and scanning electron microscope (SEM). By changing parameters such as temperature, concentration of polyoxometalates and treating time the size of SNPs can be controlled. In addition, there are no changes in the structures of the starch granules as confirmed by IR or1H NMR. Freeze-dried SNPs are amorphous as characterized by wide-angle X-ray diffraction (WXRD). [ABSTRACT FROM AUTHOR]

A flyback converter that operates in the boundary conduction mode or discontinuous conduction mode has been widely used in microinverters. Placing two flyback converters in parallel and utilizing interleaving can extend the power range of microinverters. Interleaving phases between the two converters should be carefully regulated in order to reduce the switching current ripple. In this paper, two open-loop phase synchronization methods are put forward and compared for the interleaved flyback microinverters utilizing the master-slave control principle. The comparison result shows that stable phase regulation can be achieved if synchronization is triggered at the instant when the master converter's primary switch is turned OFF. However, the switching loss will be increased with the transformers' magnetizing inductances mismatch between the two interleaved converters. To solve this problem, a novel closed-loop interleaving phase synchronization control method is proposed in this paper to guarantee high efficiency and stable operation at the same time. Simulation platform together with a 200-W prototype have been built to verify the proposed control methods. These results demonstrate that the proposed closed-loop interleaving phase synchronization control method can achieve high efficiency while maintaining stable phase synchronization for the interleaved flyback microinverter. [ABSTRACT FROM AUTHOR]

A synthetic route to FeP-GS hybrid sheets that show good stability and high electrocatalytic activity for hydrogen evolution reaction is reported. The materials are prepared via thermal phosphidation of pre-synthesized Fe3O4-GS hybrid sheets. [ABSTRACT FROM AUTHOR]

A technology of foam fractionation coupled with crystallization was developed for effectively recovering materials from wastewaters with low concentrations. The wastewater containing folic acid (FA) was used as a system and cetyltrimethyl ammonium bromide (CTAB) was chosen as a collector to recover FA from its wastewater. The results showed that the technology could effectively enrich and purify FA with a low concentration of 6 mg/L from its wastewater. In foam fractionation, the enrichment ratio and recovery percentage of FA were 86.1% and 69.1%, respectively. CTAB could be reused using a two-stage foam fractionation. In crystallization, the recovered FA had 98.0% in purity and it met the quality standard (GB 15570-95). The total recovery percentage of FA was 66.0% by the technology of foam fractionation coupled with crystallization. The technology could be effective not only for recovering FA from its wastewater but also for recovering other trace materials from their wastewaters. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this paper is to deal with the supply chain management (SCM) with quantity discount policy under the complex fuzzy environment, which is characterized as the bi-fuzzy variables. By taking into account the strategy and the process of decision making, a bi-fuzzy nonlinear multiple objective decision making (MODM) model is presented to solve the proposed problem. Design/methodology/approach: The bi-fuzzy variables in the MODM model are transformed into the trapezoidal fuzzy variables by the DMs's degree of optimism a 1 and a 2, which are de-fuzzified by the expected value index subsequently. For solving the complex nonlinear model, a multi-objective adaptive particle swarm optimization algorithm (MO-APSO) is designed as the solution method. Findings: The proposed model and algorithm are applied to a typical example of SCM problem to illustrate the effectiveness. Based on the sensitivity analysis of the results, the bi-fuzzy nonlinear MODM SCM model is proved to be sensitive to the possibility level a 1. Practical implications: The study focuses on the SCM under complex fuzzy environment in SCM, which has a great practical significance. Therefore, the bi-fuzzy MODM model and MO-APSO can be further applied in SCM problem with quantity discount policy. Originality/value: The bi-fuzzy variable is employed in the nonlinear MODM model of SCM to characterize the hybrid uncertain environment, and this work is original. In addition, the hybrid crisp approach is proposed to transferred to model to an equivalent crisp one by the DMs's degree of optimism and the expected value index. Since the MODM model consider the bi-fuzzy environment and quantity discount policy, so this paper has a great practical significance. [ABSTRACT FROM AUTHOR]

Lysine 2,3-aminomutase (KAM; EC 5.4.3.2) catalyzes the interconversion of L-lysine and L-β-lysine. The transcription and regulation of the kam locus, including lysine-2,3-aminoniutase-encoding genes, in Bacillus thuringiensis were analyzed in this study. Reverse transcription-PCR (RT-PCR) analysis revealed that this locus forms two operons: yodT (yodT-yodS-yodR-yodQ-yodP-kamR) and kamA (kamA-yokU-yozE). The transcriptional start sites (TSSs) of the katnA gene were determined using 5' rapid amplification of cDNA ends (RACE). A typical --12/--24 σK binding site was identified in the promoter PkamA, which is located upstream of the kamA gene TSS. A β-galactosidase assay showed that PkamA, which directs the transcription of the katnA operon, is controlled by the σ54 factor and is activated through the σ54-dependent transcriptional regulator KamR. The kamA operon is also controlled by σK and regulated by the GerE protein in the late stage of sporulation. kamR and kamA mutants were prepared by homologous recombination to examine the role of the kam locus. The results showed that the sporulation rate in B. thuringiensis HD(ΔkamR) was slightly decreased compared to that in HD73, whereas that in HD(ΔkamA) was similar to that in HD73. This means that other genes regulated by KamR are important for sporulation. [ABSTRACT FROM AUTHOR]

Big or high conductance potassium (BK) channels are activated by voltage and intracellular calcium (Ca2+). Phosphatidylinositol 4,5-bisphosphate (PIP2), a ubiquitous modulator of ion channel activity, has been reported to enhance Ca2+-driven gating of BK channels, but a molecular understanding of this interplay or even of the PIP2 regulation of this channel's activity remains elusive. Here, we identify structural determinants in the KDRDD loop (which follows the αA helix in the RCK1 domain) to be responsible for the coupling between Ca2+ and PIP2 in regulating BK channel activity. In the absence of Ca2+, RCK1 structural elements limit channel activation through a decrease in the channel's PIP2 apparent affinity. This inhibitory influence of BK channel activation can be relieved by mutation of residues that (a) connect either the RCK1 Ca2+ coordination site (Asp367 or its flanking basic residues in the KDRDD loop) to the PIP2-interacting residues (Lys392 and Arg393) found in the αB helix or (b) are involved in hydrophobic interactions between the αA and αB helix of the RCK1 domain. In the presence of Ca2+, the RCK1-inhibitory influence of channel-PIP2 interactions and channel activity is relieved by Ca2 + engaging Asp367. Our results demonstrate that, along with Ca2+ and voltage, PIP2 is a third factor critical to the integral control of BK channel activity. [ABSTRACT FROM AUTHOR]

Background: Stable angina pectoris is experienced as trans-sternal or retro-sternal pressure or pain that may radiate to the left arm, neck or back. Although available evidence relating to its effectiveness and mechanism are weak, traditional Chinese medicine is used as an alternative therapy for stable angina pectoris. We report a protocol of a randomized controlled trial using traditional Chinese medicine to investigate the effectiveness, mechanism and safety for patients with stable angina pectoris. Methods/Design: This is a north-east Chinese, multi-center, multi-blinded, placebo-controlled and superiority randomized trail. A total of 240 patients with stable angina pectoris will be randomly assigned to three groups: two treatment groups and a control group. The treatment groups will receive Chinese herbal medicine consisting of Yi-Qi-Jian-Pi and Qu-Tan-Hua-Zhuo granule and Yi-Qi-Jian-Pi and Qu-Tan-Hua-Yu granule, respectively, and conventional medicine. The control group will receive placebo medicine in addition to conventional medicine. All 3 groups will undergo a 12-week treatment and 2-week follow-up. Four visits in sum will be scheduled for each subject: 1 visit each in week 0, week 4, week 12 and week 14. The primary outcomes include: the frequency of angina pectoris attack; the dosage of nitroglycerin; body limited dimension of Seattle Angina Questionnaire. The secondary outcomes include: except for the body limited dimension of SAQ, traditional Chinese medicine pattern questionnaire and so on. Therapeutic mechanism outcomes, safety outcomes and endpoint outcomes will be also assessed. Discussion: The primary aim of this trial is to develop a standard protocol to utilize high-quality EBM evidence for assessing the effectiveness and safety of SAP via TCM pattern differentiation as well as exploring the efficacy mechanism and regulation with the molecular biology and systems biology. [ABSTRACT FROM AUTHOR]

The modified multiple ( $G^{\prime }/G$)-expansion method is proposed in this paper to construct exact solutions of nonlinear evolution equations. The validity and advantage of the proposed method are illustrated by its application to the Sharma-Tasso-Olver equation. As a result, various exact solutions including hyperbolic functions, trigonometric functions and their mixture with parameters are obtained. When some parameters are taken as special values, the known double solitary-like wave solutions are derived from the double hyperbolic function solution. It is shown that the method introduced in this paper has general significance in searching for exact solutions to the nonlinear evolution equations. [ABSTRACT FROM AUTHOR]

We have proposed a continuous-index system to mimic an arbitrary "potential well" for realizing versatile manipulations on acoustic waves within a broadband. An analytical description of the acoustic propagation in the system is developed, and its validity is verified by using full-wave simulation. Both the theoretical and numerical results show that by tailoring the refractive-index profile, the system either bends the incident wave like a repulsive potential, or attracts and traps the wave like an attractor. Our design may have potential implication in various situations such as medical ultrasound imaging and sound absorbing. [ABSTRACT FROM AUTHOR]

We here demonstrate a simple, efficient and eco-friendly protocol for the direct synthesis of imines from amines via a facile α-MnO2 catalyzed-procedure at rt. Up to 13 benzylic, heterocyclic, and normal aliphatic imines were synthesized with 95-99% selectivity at 82-99% conversion. [ABSTRACT FROM AUTHOR]

The crowbar protection is commonly used for wind turbines with a doubly-fed induction generator (DFIG) to enhance the low-voltage ride-through capability of the wind turbines. Thus, the fault-current characteristics of DFIG with the crowbar protection under symmetric- and asymmetric-fault states are studied in this paper. Firstly, a DFIG dynamic model in the stator stationary reference frame is developed and the dynamic characteristics of DFIG stator flux linkage are studied when the crowbar protection is activated. Based on it, the DFIG fault-current characteristics under symmetric- and asymmetric-fault states are analyzed and analytical expressions are obtained. Finally, the simulation results show that the accuracy of the theoretical analysis results is satisfactory to meet the requirements of the study of the relay-protection principle and calculation. [ABSTRACT FROM AUTHOR]

Background: Menstrual-related migraine is a common form of migraine affecting >50% of female migraineurs. Acupuncture may be a choice for menstrual-related migraine, when pharmacological prophylaxis is not suitable. However, the efficacy of acupuncture has not been confirmed. We design and perform a randomized controlled clinical trial to evaluate the efficacy of acupuncture compared with naproxen in menstrual-related migraine patients. Methods/Design: This is a multicenter, single blind, randomized controlled clinical trial. A total of 184 participants will be randomly assigned to two different groups. Participants will receive verum acupuncture and placebo medicine in the treatment group, while participants in the control group will be treated with sham acupuncture and medicine (Naproxen Sustained Release Tablets). All treatments will be given for 3 months (menstrual cycles). The primary outcome measures are the change of migraine days inside the menstrual cycle and the proportion of responders (defined as the proportion of patients with at least a 50% reduction in the number of menstrual migraine days). The secondary outcome measures are the change of migraine days outside the menstrual cycle, duration of migraine attack, the Visual Analogue Scale (VAS), and intake of acute medication. The assessment will be made at baseline (before treatment), 3 months (menstrual cycles), and 4 months (menstrual cycles) after the first acupuncture session. Discussion: The results of this trial will be helpful to supply the efficacy of acupuncture for menstrual-related migraine prophylaxis. [ABSTRACT FROM AUTHOR]

Biodegradablestereocomplex micelles (SCMs) based on amphiphilicdextran-block-polylactide (Dex-b-PLA) were designed and used for efficient intracellular drug deliveries.The Dex-b-PLA copolymers were successfully synthesizedby click reaction. The structures of the resultant copolymers wereverified by 1H NMR and FT-IR spectra. The formation ofstable micelles through self-assembly driven by the stereocomplexationbetween enantiomeric l- and d-PLA blocks was characterizedby transmission electron microscopy (TEM), dynamic laser scattering(DLS), and fluorescence techniques. It was interesting to observethat the SCMs showed lower critical micelle concentration values (CMCs)because of the stereocomplex interaction between PLLA and PDLA. Differentialscanning calorimetry (DSC) and X-ray diffraction (XRD) analysis providedinformation on the thermal and crystal properties of the copolymersand SCMs. The improved stability of SCMs should be attractive forintracellular drug delivery. Thus, a model anticancer drug doxorubicin(DOX) was loaded into micelles, and the in vitrodrugrelease in was also studied. The release kinetics of DOX showed DOX-loadedSCMs exhibited slower DOX release. Confocal laser scanning microscopy(CLSM) and flow cytometry studies also showed that the DOX-loadedSCMs exhibited a slower drug release behavior. Meanwhile, the MTTassay demonstrated that DOX-loaded SCMs show lower cellular proliferationinhibition against HepG2. In sum, the micelles through self-assemblydriven by stereocomplex interaction would have great potential tobe used as stable delivery vehicles for pharmaceutical and biomedicalapplications. [ABSTRACT FROM AUTHOR]

Background: High-throughput sequencing (HTS) technologies are spearheading the accelerated development of biomedical research. Processing and summarizing the large amount of data generated by HTS presents a nontrivial challenge to bioinformatics. A commonly adopted standard is to store sequencing reads aligned to a reference genome in SAM (Sequence Alignment/Map) or BAM (Binary Alignment/Map) files. Quality control of SAM/BAM files is a critical checkpoint before downstream analysis. The goal of the current project is to facilitate and standardize this process. Results: We developed bamchop, a robust program to efficiently summarize key statistical metrics of HTS data stored in BAM files, and to visually present the results in a formatted report. The report documents information about various aspects of HTS data, such as sequencing quality, mapping to a reference genome, sequencing coverage, and base frequency. Bamchop uses the R language and Bioconductor packages to calculate statistical matrices and the Sweave utility and associated LaTeX markup for documentation. Bamchop's efficiency and robustness were tested on BAM files generated by local sequencing facilities and the 1000 Genomes Project. Source code, instruction and example reports of bamchop are freely available from https://github.com/CBMi-BiG/ bamchop. Conclusions: Bamchop enables biomedical researchers to quickly and rigorously evaluate HTS data by providing a convenient synopsis and user-friendly reports. [ABSTRACT FROM AUTHOR]

A feasible nucleophilic trifluoromethylating protocol has been developed using trifluoroacetaldehyde hydrate as an atom-economical trifluoromethyl source. The reaction was found to be applicable to the nucleophilic trifluoromethylation of a broad spectrum of carbonyl compounds with satisfactory yields in general. DFT calculations have been performed to provide mechanistic insight into the present and related reactions employing 2,2,2-trifluoro-1-methoxyethanol and hexafluoroacetone hydrate. [ABSTRACT FROM AUTHOR]

Background/objective: MicroRNAs (miRNAs) are small noncoding RNAs (ribonucleic acids), approximately 22 nucleotides in length, that function as regulators of gene expression. Dysregulation of miRNAs has been associated with the initiation and progression of oncogenesis in humans. The cell division cycle (CDC)25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. Methods: Using miRNA target prediction software, we found that miR-141 could target the 3' untranslated region (3'UTR) sequence of CDC25B. To shed light on the role of miR-141 in renal cell carcinogenesis, the expression of miR-141 was examined by real-time polymerase chain reaction (RT-PCR) in renal cell carcinoma and normal tissues. The impact of miR-141 re-expression on 769-P cells was analyzed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony-forming assay. A luciferase reporter assay was applied to prove the functionality of the miR-141 binding site. Results: miR-141 is significantly downregulated in renal cell carcinoma. miR-141 re-expression suppressed cell growth in 769-P cells. Luciferase expression from a reporter vector containing the CDC25B-3'UTR was decreased when this construct was transfected with miR-141 in 769-P cells. The overexpression of miR-141 suppressed the endogenous CDC25B protein level in 769-P cells. Conclusion: For the first time, we demonstrated that CDC25B is a direct target of miR-141 in renal cell carcinoma. The transcriptional loss of miR-141 and the resultant increase in CDC25B expression facilitates increased genomic instability at an early stage of renal cell carcinoma development. [ABSTRACT FROM AUTHOR]

Spermine synthase (SMS) is an enzyme which function is to convert spermidine into spermine. It was shown that gene defects resulting in amino acid changes of the wild type SMS cause Snyder-Robinson syndrome, which is a mild-to- moderate mental disability associated with osteoporosis, facial asymmetry, thin habitus, hypotonia, and a nonspecific movement disorder. These disease-causing missense mutations were demonstrated, both in silico and in vitro, to affect the wild type function of SMS by either destabilizing the SMS dimer/monomer or directly affecting the hydrogen bond network of the active site of SMS. In contrast to these studies, here we report an artificial engineering of a more efficient SMS variant by transferring sequence information from another organism. It is confirmed experimentally that the variant, bearing four amino acid substitutions, is catalytically more active than the wild type. The increased functionality is attributed to enhanced monomer stability, lowering the pKa of proton donor catalytic residue, optimized spatial distribution of the electrostatic potential around the SMS with respect to substrates, and increase of the frequency of mechanical vibration of the clefts presumed to be the gates toward the active sites. The study demonstrates that wild type SMS is not particularly evolutionarily optimized with respect to the reaction spermidine → spermine. Having in mind that currently there are no variations (non-synonymous single nucleotide polymorphism, nsSNP) detected in healthy individuals, it can be speculated that the human SMS function is precisely tuned toward its wild type and any deviation is unwanted and disease-causing. [ABSTRACT FROM AUTHOR]

Increasing evidence demonstrated that inactivation of tumor suppressor genes (TSGs) by aberrant promoter methylation is an early event during carcinogenesis. Aiming at developing early diagnostic or prognostic tools for various tumors, we took an EBV-associated tumor, nasopharyngeal carcinoma (NPC), as a model and developed a powerful assay based on "multiplex methylation specific-PCR (MMSP)". The MMSP assay was designed to detect tumor-specific methylation status of several NPC-related genes and was capable of acquiring multiplex information simultaneously through a single PCR reaction with the tiny tumor DNA derived from the direct body fluid close to the primary tumor. In this study, we collected paired nasopharyngeal (NP) swabs and NPC biopsies from 49 NPC patients and twenty noncancerous controls. A panel of markers including two EBV, and two cellular TSG markers were applied in this NPC-specific-MMSP assay. We optimized the working condition of MMSP so that it provides information equal to that from the corresponding separate PCRs. The results showed that MMSP patterns of NPC swab were largely consistent with those of corresponding biopsies and significantly distinguished themselves from those of 20 noncancerous volunteers. Among the 69 samples (49 NPCs and 20 normal controls), the sensitivity of detecting NPC from NP swabs is 98%. The specificity is as high as 100%. In conclusion, being characterized by its noninvasiveness, high reproducibility and informativeness, MMSP assay is a reliable and potential diagnostic tool for NPC. It paves the way for the development of population screening and early diagnosis approaches for various tumor types. [ABSTRACT FROM AUTHOR]

Although human amniotic mesenchymal stem cells (AMMs) have been recognised as a promising stem cell resource, their therapeutic potential for wound healing has not been widely investigated. In this study, we evaluated the therapeutic potential of AMMs using a diabetic mouse wound model. Quantitative real-time PCR and ELISA results revealed that the angiogenic factors, IGF-1, EGF and IL-8 were markedly upregulated in AMMs when compared with adipose-derived mesenchymal stem cells (ADMs) and dermal fibroblasts. In vitro scratch wound assays also showed that AMM-derived conditioned media (CM) significantly accelerated wound closure. Diabetic mice were generated using streptozotocin and wounds were created by skin excision, followed by AMM transplantation. AMM transplantation significantly promoted wound healing and increased re-epithelialization and cellularity. Notably, transplanted AMMs exhibited high engraftment rates and expressed keratinocyte-specific proteins and cytokeratin in the wound area, indicating a direct contribution to cutaneous closure. Taken together, these data suggest that AMMs possess considerable therapeutic potential for chronic wounds through the secretion of angiogenic factors and enhanced engraftment/differentiation capabilities. [ABSTRACT FROM AUTHOR]

A common limitation of power coupling effect in some known multiple-input dc-dc converters has been addressed in many literatures. In order to overcome this limitation, a new concept for decoupling the primary windings in the integrated multiple-winding transformers based on 3-D space orthogonal flux is proposed in this letter. And thus, a new geometry core and relative winding arrangements are proposed in accordance with the orthogonal flux decoupling technology. Due to the four secondary windings are arranged in a quadratic pattern at the base core plate with the two perpendicular primary windings, a name of “four quadrants integrated transformers” (FQIT) is, therefore, given to the proposed construction. Since the two primary windings are uncoupled, the FQIT allows the two input power stages to transfer the energy into the output load simultaneously or at any time-multiplexing scheme, which can optimize the utilization of input sources, simplify the system structure, and reduce the overall cost, so they are attractive for the hybrid renewable power system. Section IV initiates a discussion for the advantages of the FQIT. In order to verify the feasibility of the FQIT in multiple-input converter, a dual-input isolated boost dc-dc converter with the FQIT is designed and tested. The results have excellently demonstrated that the two input power stages can be operated independently and the correctness of all the analysis in the letter. [ABSTRACT FROM AUTHOR]

A biodegradable, biocompatible poly(chitosan-g-lactic acid) (PCLA) scaffold was prepared and evaluated in vitro and in vivo. The PCLA scaffold was obtained by grafting lactic acid (LA) onto the amino groups on chitosan (CS) without a catalyst. The PCLA scaffolds were characterized by Fourier Transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The biodegradabilty was determined by mass loss in vitro, and degradation in vivo as a function of feed ratio of LA/CS. Bone marrow mesenchymal stem cell (BMSC) culture experiments and histological examination were performed to evaluate the PCLA scaffolds' biocompatibility. The results indicated that PCLA was promising for tissue engineering application. [ABSTRACT FROM AUTHOR]

Electrical power systems in future uninterruptible power supplies or electrical vehicles may employ hybrid energy sources, such as fuel cells and supercapacitors. It will be necessary to efficiently draw the energy from these two sources as well as recharge the energy storage elements by the dc bus. In this paper, a bidirectional isolated dc-dc converter controlled by phase-shift angle and duty cycle for the fuel-cell hybrid energy system is analyzed and designed. The proposed topology minimizes the number of switches and their associated gate driver components by using two high-frequency transformers that combine a half-bridge circuit and a full-bridge circuit together on the primary side. The voltage doubler circuit is employed on the secondary side. The current-fed input can limit the input current ripple that is favorable for fuel cells. The parasitic capacitance of the switches is used for zero voltage switching (ZVS). Moreover, a phase-shift and duty-cycle modulation method is utilized to control the bidirectional power flow flexibly and it also makes the converter operate under a quasi-optimal condition over a wide input voltage range. This paper describes the operation principle of the proposed converter, the ZVS conditions, and the quasi-optimal design in depth. The design guidelines and considerations regarding the transformers and other key components are given. Finally, a 1-kW 30~50-V-input 400-V-output laboratory prototype operating at 100-kHz switching frequency is built and tested to verify the effectiveness of the presented converter. [ABSTRACT FROM AUTHOR]

Single-pointmutation in genome, for example, single-nucleotide polymorphism (SNP) or rare geneticmutation, is the change of a single nucleotide for another in the genome sequence. Some of them will produce an amino acid substitution in the corresponding protein sequence (missense mutations); others will not. This paper focuses on genetic mutations resulting in a change in the amino acid sequence of the corresponding protein and how to assess their effects on protein wild-type characteristics. The existing methods and approaches for predicting the effects of mutation on protein stability, structure, and dynamics are outlined and discussed with respect to their underlying principles. Available resources, either as stand-alone applications or webservers, are pointed out as well. It is emphasized that understanding the molecular mechanisms behind these effects due to these missense mutations is of critical importance for detecting disease-causingmutations. The paper provides several examples of the application of 3D structure-based methods to model the effects of protein stability and protein-protein interactions caused by missense mutations as well. [ABSTRACT FROM AUTHOR]

In most power electronics converters, the overall volume is mainly determined by the number of parts and the size of passive components. Integrated magnetics and planar magnetics techniques, therefore, have been an excellent option in order to reduce the counts and the size of magnetic components, hereby increasing the power density of converters. In this paper, a new planar-integrated magnetics (PIM) module for a phase-shift plus duty-cycle-controlled hybrid bidirectional dc-dc converter is proposed, which assembles one boost inductor and two transformers into an E-I-E core geometry, reducing the number of parts, the total volume of converter, as well as the total core loss of the magnetic components. AC losses in the windings and leakage inductance of the transformers are kept low by interleaving the primary and secondary turns of the transformers. To verify the validity of the design approach and theoretical analysis, a laboratory prototype employing the PIM module is implemented for a fuel cell application with 20-40-V input voltage and 400-V output voltage. Detailed results from the experimental comparisons demonstrate that the PIM module is fully functional and electromagnetically equivalent to the discrete magnetics and a significant reduction of size can be achieved by using the PIM module. [ABSTRACT FROM AUTHOR]

In TNF-treated cells, TNFR1, TNFR-associated death domain protein (TRADD), Fas-associated death domain protein, and receptor-interacting protein kinase proteins form the signaling complex via modular interaction within their C-terminal death domains. In this paper, we report that the death domain SXXE/D motifs (i.e., S381DHE motif of TNFR1-death domain as well as S215LKD and S296LAE motifs of TRADD-death domain) are phosphorylated, and this is required for stable TNFR1-TRADD complex formation and subsequent activation of NF-κB. Phospho-S215LKD and phospho-S296LAE motifs are also critical to TRADD for recruiting Fas-associated death domain protein and receptor-interacting protein kinase. I?B kinase β plays a critical role in TNFR1 phosphorylation of S381, which leads to subsequent T cell migration and accumulation. Consistently, we observed in inflammatory bowel disease specimens that TNFR1 was constitutively phosphorylated on S381 in those inflammatory T cells, which had accumulated in high numbers in the inflamed mucosa. Therefore, SXXE/D motifs found in the cytoplasmic domains of many TNFR family members and their adaptor proteins may serve to function as a specific interaction module for the α-helical death domain signal transduction. [ABSTRACT FROM AUTHOR]