Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of peginterferon alpha‐2b and entecavir hydrate combination therapy on persistent viral suppression in patients with chronic hepatitis B

The ideal approach to treat chronic hepatitis B remains controversial. This pilot study aimed to evaluate the effectiveness of peginterferon (PEG‐IFN) α‐2b and entecavir hydrate (ETV) as a combination therapy for patients with chronic hepatitis B, particularly in the context of virological response and the reduction of intrahepatic covalently closed circular DNA (cccDNA). A total of 17 patients with hepatitis B virus (HBV) genotype C were enrolled in this study. All subjects were treated with this combination therapy for 48 weeks and observed for an additional 24 weeks. All patients underwent liver biopsy before and after the therapy period. Changes in cccDNA levels and liver histology were monitored between biopsies. Among the 11 patients who exhibited pre‐therapy hepatitis B e antigen (HBeAg), 8 (73%) showed evidence of HBeAg seroconversion by the end of the follow‐up period. Serum HBV DNA levels decreased by 5.2 and 3.3 log copies/ml (mean) by the end of the therapy and follow‐up periods, respectively. In addition, intrahepatic cccDNA decreased significantly to 1.4 log copies/µg (mean) by the end of the therapy period. Among the 11 patients who did not experience viral relapse, only 2 (18%) exhibited high levels of cccDNA (>4.5 log copies/µg) by the end of the treatment period. In contrast, all relapsed subjects exhibited significantly higher levels of cccDNA than subjects who did not relapse (P = 0.027). The combination regimen is a promising approach to treat chronic hepatitis B and may achieve significant reduction in serum HBV DNA and intrahepatic cccDNA. J. Med. Virol. 85: 987–995, 2013. © 2013 Wiley Periodicals, Inc.
Enhanced Modeling of Linear Permanent-Magnet Synchronous Motors

Modeling of air-gap flux density distribution produced by magnet poles is essential for analysis and design of linear permanent-magnet synchronous motors. This is usually done by time-consuming numerical methods which are difficult to be incorporated in iterative motor design procedures or by approximate models which lack desirable accuracy. This paper presents an alternative method to model the air-gap flux density distribution which is both accurate and simple enough to be integrated into iterative motor design procedures. It consists of the solution of an improved magnetic equivalent circuit and an air-gap flux density distribution function (FDDF). The end teeth effects and magnetic saturation of iron core can be taken into account in the modeling. Different motor characteristics are calculated by means of the proposed FDDF. The accuracy of the proposed method in modeling of the machines is verified by the finite-element method and its superiority over a recent method based on an extensive machine model is demonstrated
Women's Health Education Initiatives: Why Have They Stalled?

Since the U.S. Congress first requested an assessment of women's health content in medical school curricula ten years ago, surveys indicate at least a two-fold increase in the number of schools with a women's health curriculum and no change in the number that offer a women's health clinical elective or rotation. Despite a marked increase in the number of schools with an office or program responsible for integration of women's health and gender-specific content into curricula, change has been modest. Reasons for this slow progress include uncertainty about the domain of women's health and what should be included in a curriculum, a lack of practical guidelines for implementation, and institutional resistance to change. The dominant factors that will influence future curriculum development are the increasing scientific knowledge base on sex and gender differences and the emerging scientific field of sex-based biology, both of which have potential to benefit the health of women. Evidence-based data on significant sex and gender differences will provide compelling reasons for schools to integrate this information into curricula, and new educational initiatives must further develop educational models to help implement change. As women's health becomes synonymous with the term “sex and gender differences,” the challenge to schools is to address equally in their curricula those unique aspects of women's health that were part of the original intent of the congressional mandate.
Plant protein 2‐Cys peroxiredoxin TaBAS1 alleviates oxidative and nitrosative stresses incurred during cryopreservation of mammalian cells

There is increasing demand for cryopreserved cells such as liver and pancreatic cells for clinical applications. Cryopreservation at ultra‐low temperatures requires use of cryoprotectants (e.g., dimethyl sulfoxide (DMSO)) to maintain cell integrity during freezing and thawing processes. Standard cryoprotectants are cytotoxic and more effective cryopreservation technologies are urgently needed for long‐term storage of cells. As an alternative, soluble protein extracts (WPE) from winter wheat successfully replaced DMSO as a cryoprotectant for several mammalian cell types. To identify novel cryoactive proteins, the WPE was separated by chromatography and cryoactive fractions were analyzed by mass spectrometry. The wheat protein 2‐Cys peroxiredoxin BAS1 (renamed TaBAS1) was identified as a potential cryoactive candidate. Recombinant proteins were prepared and found to possess dual functions as a peroxidase antioxidant and molecular chaperone, and display cryoprotective properties for hepatocytes and insulin‐secreting INS832/13 cells. Following cryopreservation with TaBAS1, cells were plateable and showed high post‐thaw viability, good adhesion properties, and well‐maintained cell‐specific metabolic functions. The overall quality of these cell types was equivalent or improved compared to cells that were cryopreserved with DMSO. The antioxidant and chaperone functions of TaBAS1 likely explain its efficacy in reducing oxidative/nitrosative stresses in cryopreserved cells. The plant protein TaBAS1 could be a promising molecule to include in cryostorage protocols. Biotechnol. Bioeng. 2016;113: 1511–1521. © 2015 Wiley Periodicals, Inc.
Dynamics of the Ternary Complex Formed by c-Myc Interactor JPO2, Transcriptional Co-activator LEDGF/p75, and Chromatin*

Background: The function of transcription factors can be investigated by monitoring their movement inside the nucleus of cells with biophysical techniques. Results: A model for interaction of JPO2 with chromatin in the absence and presence of its interaction partner LEDGF/p75 is proposed. Conclusion: JPO2 adopts the dynamics of LEDGF/p75. Significance: Our approach is generic for the study of transcription factor dynamics. Lens epithelium-derived growth factor (LEDGF/p75) is a transcriptional co-activator involved in targeting human immunodeficiency virus (HIV) integration and the development of MLL fusion-mediated acute leukemia. A previous study revealed that LEDGF/p75 dynamically scans the chromatin, and upon interaction with HIV-1 integrase, their complex is locked on chromatin. At present, it is not known whether LEDGF/p75-mediated chromatin locking is typical for interacting proteins. Here, we employed continuous photobleaching and fluorescence correlation and cross-correlation spectroscopy to investigate in vivo chromatin binding of JPO2, a LEDGF/p75- and c-Myc-interacting protein involved in transcriptional regulation. In the absence of LEDGF/p75, JPO2 performs chromatin scanning inherent to transcription factors. However, whereas the dynamics of JPO2 chromatin binding are decelerated upon interaction with LEDGF/p75, very strong locking of their complex onto chromatin is absent. Similar results were obtained with the domesticated transposase PogZ, another cellular interaction partner of LEDGF/p75. We furthermore show that diffusive JPO2 can oligomerize; that JPO2 and LEDGF/p75 interact directly and specifically in vivo through the specific interaction domain of JPO2 and the C-terminal domain of LEDGF/p75, comprising the integrase-binding domain; and that modulation of JPO2 dynamics requires a functional PWWP domain in LEDGF/p75. Our results suggest that the dynamics of the LEDGF/p75-chromatin interaction depend on the specific partner and that strong chromatin locking is not a property of all LEDGF/p75-binding proteins.
The R-Ras interaction partner ORP3 regulates cell adhesion

Oxysterol-binding protein (OSBP)-related protein 3 (ORP3) is highly expressed in epithelial, neuronal and hematopoietic cells, as well as in certain forms of cancer. We assessed the function of ORP3 in HEK293 cells and in human macrophages. We show that ORP3 interacts with R-Ras, a small GTPase regulating cell adhesion, spreading and migration. Gene silencing of ORP3 in HEK293 cells results in altered organization of the actin cytoskeleton, impaired cell-cell adhesion, enhanced cell spreading and an increase of β1 integrin activity–effects similar to those of constitutively active R-Ras(38V). Overexpression of ORP3 leads to formation of polarized cell-surface protrusions, impaired cell spreading and decreased β1 integrin activity. In primary macrophages, overexpression of ORP3 leads to the disappearance of podosomal structures and decreased phagocytotic uptake of latex beads, consistent with a role in actin regulation. ORP3 is phosphorylated when cells lose adhesive contacts, suggesting that it is subject to regulation by outside-in signals mediated by adhesion receptors. The present findings demonstrate a new function of ORP3 as part of the machinery that controls the actin cytoskeleton, cell polarity and cell adhesion.
Sequential gene activation and gene imprinting during early embryo development in maize.

Gene imprinting is a widely observed epigenetic phenomenon in maize endosperm; however, whether it also occurs in the maize embryo remains controversial. Here, we used high-throughput RNA sequencing on laser capture microdissected and manually dissected maize embryos from reciprocal crosses between inbred lines B73 and Mo17 at six time points (3-13 days after pollination, DAP) to analyze allelic gene expression patterns. Co-expression analysis revealed sequential gene activation during maize embryo development. Gene imprinting was observed in maize embryos, and a greater number of imprinted genes were identified at early embryo stages. Sixty-four strongly imprinted genes were identified (at the threshold of 9:1) on manually dissected embryos 5-13 DAP (more imprinted genes at 5 DAP). Forty-one strongly imprinted genes were identified from laser capture microdissected embryos at 3 and 5 DAP (more imprinted genes at 3 DAP). Furthermore, of the 56 genes that were completely imprinted (at the threshold of 99:1), 36 were not previously identified as imprinted genes in endosperm or embryos. In situ hybridization demonstrated that most of the imprinted genes were expressed abundantly in maize embryonic tissue. Our results shed lights on early maize embryo development and provide evidence to support that gene imprinting occurs in maize embryos.
Development and Application of a PCR-Targeted Gene Disruption Method for Studying CelR Function in Thermobifida fusca

ABSTRACT Thermobifida fusca is a high-G+C-content, thermophilic, Gram-positive soil actinobacterium with high cellulolytic activity. In T. fusca, CelR is thought to act as the primary regulator of cellulase gene expression by binding to a 14-bp inverted repeat [5′-(T)GGGAGCGCTCCC(A)] that is upstream of many known cellulase genes. Previously, the ability to study the roles and regulation of cellulase genes in T. fusca has been limited largely by a lack of established genetic engineering methods for T. fusca. In this study, we developed an efficient procedure for creating precise chromosomal gene disruptions and demonstrated this procedure by generating a celR deletion strain. The celR deletion strain was then characterized using measurements for growth behavior, cellulase activity, and gene expression. The celR deletion strain of T. fusca exhibited a severely crippled growth phenotype with a prolonged lag phase and decreased cell yields for growth on both glucose and cellobiose. While the maximum endoglucanase activity and cellulase activity were not significantly changed, the endoglucanase activity and cellulase activity per cell were highly elevated. Measurements of mRNA transcript levels in both the celR deletion strain and the wild-type strain indicated that the CelR protein potentially acts as a repressor for some genes and as an activator for other genes. Overall, we established and demonstrated a method for manipulating chromosomal DNA in T. fusca that can be used to study the cellulolytic capabilities of this organism. Components of this method may be useful in developing genetic engineering methods for other currently intractable organisms.
Running and Jumping Dynamics of a Symmetric 5-bar Leg Design

Dynamic legged robots are capable of a wide range of behaviors, such as running, climbing and jumping. In each of these cases the leg morphology, compliance, and postural control all interact to enable dexterous, dynamic motion. In this paper we examine the design trade-offs between these factors in producing stable running and powerful jumping. Specifically we examine the stability of a SLIP-like running model with a unique 5-bar leg configuration that is designed for hopping energetics. We show, via numerical simulation and with a single leg experimental platform, the effect stiffness change, link geometry, and configuration changes have on both the stability of running and height of jumping, and indicate a scheme that utilizes postural adjustments to switch between effective running and hopping regimes.
Wideband Triangular-Cavity-Cascaded Antennas

A triangular-cavity-cascaded antenna is proposed and analyzed for wideband applications. By alternatively and periodically shorting a metallic plate on its edges with small slices, isosceles-triangular field patterns are generated and cascaded for wideband antenna design. Synchronous electric edge fields which contribute to radiation occupy almost all the areas of both sides of the plate. Compared with a typical microstrip antenna with a rectangular cavity, the triangular-cavity-cascaded antenna is a relatively open structure with less shorting boundary around. As a result, the quality factor is smaller, and the impedance bandwidth is wider. In order to prove the design strategy, a 1-D cascaded antenna with 1 × 5 triangular cavities and a 2-D cascaded antenna with 2 × 5 triangular cavities are fabricated and tested. Experimental results show that the impedance bandwidths of 1-D and 2-D antennas are 35.66% and 21.43%, while the peak gains are 13.27 and 16.47 dBi, respectively.
MLP-based undersampling technique for imbalanced learning

The imbalanced learning problem is becoming pervasive in today's data mining applications. This problem refers to the uneven distribution of instances among the classes which poses difficulty in the classification of rare instances. Several undersampling as well as oversampling methods were proposed to deal with such imbalance. Many undersampling techniques do not consider distribution of information among the classes, similarly some oversampling techniques lead to the overfitting or may cause overgeneralization problem. This paper proposes an MLP-based undersampling technique (MLPUS) which will preserve the distribution of information while doing undersampling. This reduction can be done on the basis of stochastic measure evaluation. Experiments are performed on 10 real world data sets for the evaluation of performance of MLPUS.
Molecular Dynamics Simulations of the Transmembrane Domain of the Oncogenic ErbB2 Receptor Dimer in a DMPC Bilayer

Abstract Molecular dynamics simulations of an atomic model of the transmembrane domain of the oncogenic ErbB2 receptor dimer embedded in an explicit dimyristoylphosphatidylcholine (DMPC) bilayer were performed for more than 4 ns. The oncogenic Glu mutation in the membrane spanning segment plays a major role in tyrosine kinase activity and receptor dimerization, and is thought to be partly responsible for the structure of the transmembrane domain of the active receptor. MD results show that the interactions between the two transmembrane helices are characteristic of a left-handed packing as previously demonstrated from in vacuo simulations. Moreover, MD results reveal the absence of persistent hydrogen bonds between the Glu side chains in a membrane environment, which raise the question of the ability for Glu alone to stabilize the TM domain of the ErbB2 receptor. Interestingly the formation of the α-π motif in the two ErbB2 transmembrane helices confirms the concept of intrinsic sequence-induced conformational flexibility. From a careful analysis of our MD results, we suggest that the left-handed helix-helix packing could be the key to correctly orient the intracellular domain of the activated receptor dimer. The prediction of such interactions from computer simulations represents a new step towards the understanding of signaling mechanisms.
ARIES-3: ambrisentan therapy in a diverse population of patients with pulmonary hypertension.

INTRODUCTION Ambrisentan is an oral, once daily, endothelin receptor antagonist approved for treatment of pulmonary arterial hypertension (PAH). Previous studies of ambrisentan were limited to patients with Group 1 PAH and often excluded patients receiving other pulmonary hypertension (PH) therapies. AIMS ARIES-3 was an open-label study evaluating efficacy and safety of ambrisentan in patients with various PH etiologies and background PH medications. Patients received 5 mg ambrisentan once daily for 24 weeks. The primary endpoint was change from baseline in 6-minute walk distance (6MWD) at week 24. RESULTS A total of 224 patients with PH due to idiopathic and familial PAH (31%), connective tissue disease (18%), chronic hypoxemia (22%), chronic thromboembolic disease (13%), or other etiologies (16%) were enrolled and 53% of patients received stable background PAH therapies. After 24 weeks of therapy, an increase in 6MWD (+21 m; 95% CI: 12-29) and a decrease in B-type natriuretic peptide (-26%; 95% CI: -34 to -16%) was observed in the overall population compared to baseline; however, increases in 6MWD were not observed in several non-Group 1 PH subpopulations. Peripheral edema, headache, and dyspnea were the most common adverse events. CONCLUSION This study reconfirms the results of previous placebo-controlled studies, which demonstrate that ambrisentan is well tolerated and provides benefit in patients with PAH. Definitive conclusions regarding the safety and efficacy of ambrisentan in specific non-Group 1 PH etiologies cannot be determined and larger, controlled studies will be necessary to determine the efficacy and safety of ambrisentan in these populations.
Streptococcus pneumoniae Surface Protein PcpA Elicits Protection against Lung Infection and Fatal Sepsis

ABSTRACT Previous studies have suggested that pneumococcal choline binding protein A (PcpA) is important for the full virulence of Streptococcus pneumoniae, and its amino acid sequence suggests that it may play a role in cellular adherence. PcpA is under the control of a manganese-dependent regulator and is only expressed at low manganese concentrations, similar to those found in the blood and lungs. PcpA expression is repressed under high manganese concentrations, similar to those found in secretions. In this study, we have demonstrated that PcpA elicits statistically significant protection in murine models of pneumonia and sepsis. In the model of pneumonia with each of four challenge strains, statistically fewer S. pneumoniae cells were recovered from the lungs of mice immunized with PcpA and alum versus mice immunized with alum only. The immunizations reduced the median CFU by 4- to 400-fold (average of 28-fold). In the model of sepsis using strain TIGR4, PcpA expression resulted in shorter times to become moribund and subcutaneous immunization with PcpA increased survival times of mice infected with wild-type PcpA-expressing pneumococci.
Contributions of discrete tRNA(Ser) domains to aminoacylation by E.coli seryl-tRNA synthetase: a kinetic analysis using model RNA substrates.

The aminoacylation kinetics of T7 transcripts representing defined regions of Escherichia coli serine tRNAs were determined using purified E.coli seryl-tRNA synthetase (SerRS) and the kinetic values were used to estimate the relative contribution of various tRNA(Ser) domains to recognition by SerRS. The analysis revealed that the extra stem/loop structure, characteristic of type II tRNAs such as tRNA(Ser), is the domain which makes the largest contribution to kcat/Km of aminoacylation. Moreover, Km of aminoacylation was increased by a factor of about 1000 when the extra stem/loop was changed to the consensus sequence of type I tRNA extra loops indicating that the stem structure contributes significantly to the binding of tRNA(Ser) to SerRS. A model RNA, which represents only the tRNA(Ser) coaxial acceptor-T psi C stem/loop domain, was also specifically aminoacylated by SerRS having a kcat/Km about 1000-fold greater than background levels. A significant portion of the contribution of this domain to aminoacylation is attributable to the acceptor stem sequence making the acceptor stem the second most important domain for recognition by SerRS. Finally, kcat/Km was essentially unchanged when the entire anticodon stem/loop of tRNA(Ser) was deleted indicating that neither the anticodon nucleotides nor the surrounding stem/loop structure are important for recognition by SerRS.
Multimedia experience in telemedicine: A strategy for recovering live surgery transmissions

Video-based applications are increasingly popular. An interesting area is Telemedicine or eHealth applications, such as clinical sessions, second medical opinion, interactive training or surgery transmission. This scenario is featured by handle multiple video streams. In addition, other objects, as clinical images, animations, video-based exams can be used to enrich the multimedia experience. Thus, this paper approaches a strategy to record and recover the multimedia experience in telemedicine systems. The proposed strategy allows specifying multiple data streams and their interactions and enables to reproduce a multimedia experience and its plurality. The proposed strategy was applied in Arthron (a tool to manage remote and multiple streams in Telemedicine) for recording live surgery transmissions. We also discuss results of experiments held in the Lauro Wanderley Academic Hospital, Brazil.
Shifting Standards and the Inference of Incompetence: Effects of Formal and Informal Evaluation Tools

The authors distinguish between minimum and confirmatory standards of incompetence and hypothesize that for groups stereotyped as relatively competent (or deficient in incompetence), minimum standards of incompetence are lower (suspicion of incompetence is triggered sooner) but confirmatory standards are higher, relative to groups stereotyped as relatively incompetent. An initial study demonstrated this evidentiary pattern for male versus female targets. In Studies 2 and 3, participants were exposed to a poor-performing male or female (Study 2) or Black or White male (Study 3) trainee and were asked to record “notable” behaviors in either their “informal notes” (instantiating a minimum standard) or a “formal performance log” (instantiating a confirmatory standard). Consistent with predictions, fewer incompetent behaviors were recorded in the formal log than in informal notes for White male trainees. Firing decisions generally mimicked these patterns and in Study 3 were partially mediated by the accessibility of incompetent behaviors.