Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Algorithm to Optimize Fitness Function with Sampling Error and its Application to Financial Optimization Problem

In this paper we discuss the optimization problems with noisy fitness function. On financial optimization problems, Monte-Carlo method is commonly used to evaluate the optimization criteria such as value at risk. The evaluation model is often very complex which needs considerable computational overheads. In order to realize efficient optimization of financial problems, we propose a method to decide the number of samples used to estimate the optimization criteria. Selection efficiency proposed in this paper is a index that shows how close the population approaches to the convergence to a good solution. In general, it is difficult to calculate selection efficiency analytically. Thus we also employ bootstrap method to estimate selection efficiency. The resulting algorithm is applied to the optimization of the procurement plan optimization problem. The result shows that value at risk of the problem is optimized efficiently by the proposed method.
Ligand-regulated entry into the HRD ERAD pathway—the dark side of allostery

HMG-CoA reductase (HMGR) undergoes regulated degradation as part of feedback control of the sterol pathway. In yeast the stability of the Hmg2 isozyme of HMGR is controlled by the 20 carbon isoprenoid geranylgeranyl pyrophosphate (GGPP): increasing levels of GGPP causes more efficient degradation by the HRD pathway, allowing feedback regulation of HMGR. The HRD pathway is a conserved quality control pathway critical for the ER-associated degradation of misfolded ER proteins. We have explored the action of GGPP in HRD-dependent Hmg2 degradation. GGPP was highly potent as a regulatory molecule in vivo, and in vitro, GGPP altered Hmg2 folding at nanomolar concentrations. These effects of GGPP were absent in a variety of stabilized or non-regulated Hmg2 mutants. Consistent with its high potency, the effects of GGPP were highly specific; other closely related molecules were ineffective in altering Hmg2 structure. In fact, two close GGPP analogues, 2F-GGPP and GGSPP were completely inactive at all concentrations tested, and GGSPP was an antagonist of GGPPs effects in vivo and in vitro. The effects of GGPP on Hmg2 structure and degradation were reversed by chemical chaperones, indicating that GGPP caused selective Hmg2 misfolding. These data indicate that GGPP functions in a manner analogous to an allosteric ligand, causing Hmg2 misfolding through interaction with a reversible, specific binding site. Consistent with this, the Hmg2 protein forms mulitmers. We propose that this “allosteric misfolding,” or mallostery, may be a widely used tactic of biological regulation, with potential for development of small molecule pharmaceuticals that induce selective misfolding.
Generation and Characterization of a Hepatitis C Virus NS3 Protease-Dependent Bovine Viral Diarrhea Virus

ABSTRACT Unique to pestiviruses, the N-terminal protein encoded by the bovine viral diarrhea virus (BVDV) genome is a cysteine protease (Npro) responsible for a self-cleavage that releases the N terminus of the core protein (C). This unique protease is dispensable for viral replication, and its coding region can be replaced by a ubiquitin gene directly fused in frame to the core. To develop an antiviral assay that allows the assessment of anti-hepatitis C virus (HCV) NS3 protease inhibitors, a chimeric BVDV in which the coding region of Npro was replaced by that of an NS4A cofactor-tethered HCV NS3 protease domain was generated. This cofactor-tethered HCV protease domain was linked in frame to the core protein of BVDV through an HCV NS5A-NS5B junction site and mimicked the proteolytic function of Npro in the release of BVDV core for capsid assembly. A similar chimeric construct was built with an inactive HCV NS3 protease to serve as a control. Genomic RNA transcripts derived from both chimeric clones, PH/B(wild-type HCV NS3 protease) and PH/B(S139A) (mutant HCV NS3 protease) were then transfected into bovine cells (MDBK). Only the RNA transcripts from the PH/B clone yielded viable viruses, whereas the mutant clone, PH/B(S139A), failed to produce any signs of infection, suggesting that the unprocessed fusion protein rendered the BVDV core protein defective in capsid assembly. Like the wild-type BVDV (NADL), the chimeric virus was cytopathic and formed plaques on the cell monolayer. Sequence and biochemical analyses confirmed the identity of the chimeric virus and further revealed variant viruses due to growth adaptation. Growth analysis revealed comparable replication kinetics between the wild-type and the chimeric BVDVs. Finally, to assess the genetic stability of the chimeric virus, an Npro-null BVDV (BVDV−Npro in which the entire Npro coding region was deleted) was produced. Although cytopathic, BVDV−Npro was highly defective in viral replication and growth, a finding consistent with the observed stability of the chimeric virus after serial passages.
Evaluating trust elements in the context of Islamic based informational websites

In the past, many researches have examined and addressed the notion of trust multidimensional in concepts within the areas of e-commerce ranging from business to business (B2B), business to consumer (B2C) and consumer to consumer (C2C). Indeed, the element of trust is vital in ensuring the success of e-commerce. However, the web evolution has moved the interpersonal and inter-organizational transactions to knowledge and information exchange with the rise of Web Mediated Information Environment (W-MIE) that offer services such as health advice, religion information, political views and financial advice. Hence, the aim of this research is to identify trust elements within the context of Islamic based informational websites. We contend that this environment posed significant emotional values to its users in terms of the overall design strategy for the web content, interface representation and systems characteristics adherence to Islamic values, principles and guidelines. This paper reported the results of an experiment conducted within the scope of Islamic educational based websites by using semantic differential method with 10 Islamic users. The measured elements are derived through literature analysis and Islamic expert review. Through factor analysis we have found 8 trust elements which are significant for the design of Islamic web based content websites. There are “credibility”, “benevolence”, “Tauheed”, “avoid distraction”, “presentable”, “well-conveyed”, “avoid unfairness” and “avoid childish” and discussion towards design implications are further elaborated.
Histone H2AX Phosphorylation as a Predictor of Radiosensitivity and Target for Radiotherapy*

Based on the role of phosphorylation of the histone H2A variant H2AX in recruitment of DNA repair and checkpoint proteins to the sites of DNA damage, we have investigated γH2AX as a reporter of tumor radiosensitivity and a potential target to enhance the effectiveness of radiation therapy. Clinically relevant ionizing radiation (IR) doses induced similar patterns of γH2AX focus formation or immunoreactivity in radiosensitive and radioresistant human tumor cell lines and xenografted tumors. However, radiosensitive tumor cells and xenografts retained γH2AX for a greater duration than radioresistant cells and tumors. These results suggest that persistence of γH2AX after IR may predict tumor response to radiotherapy. We synthesized peptide mimics of the H2AX carboxyl-terminal tail to test whether antagonizing H2AX function affects tumor cell survival following IR. The peptides did not alter the viability of unirradiated tumor cells, but both blocked induction of γH2AX foci by IR and enhanced cell death in irradiated radioresistant tumor cells. These results suggest that H2AX is a potential molecular target to enhance the effects of radiotherapy.
Influência do professor e do ambiente em sala de aula sobre a proficiência alcançada pelos alunos avaliados no Simave-2002

Em geral os sistemas de avaliacao educacional mantem um mesmo objetivo prioritario de encontrar mecanismos para melhorar a qualidade do ensino oferecido a sociedade. Alem de identificar resultados da aprendizagem dos alunos, avalia-se o conjunto do sistema educacional. Dentro desse contexto o Sistema Mineiro de Avaliacao da Educacao Publica (Simave) foi instituido pela Secretaria de Estado de Educacao no ano de 2000. Os dados do contexto escolar mineiro que sao disponibilizados pelo Simave-2002 estao agrupados hierarquicamente, ou seja, os alunos estao agrupados em turmas, que se agrupam em escolas. O presente estudo empregou modelos hierarquicos (multinivel) com o objetivo de avaliar o impacto que caracteristicas do professor e do ambiente em sala de aula apresentam sobre a proficiencia dos alunos das 4a series do Ensino Fundamental que fizeram os testes de Lingua Portuguesa do Simave-2002. Buscando investigar os fatores que atuam na diferenciacao entre as proficiencias dos alunos foram considerados os modelos com os niveis de hierarquia: aluno (nivel 1) e turma (nivel 2). Foi encontrada explicacao para uma grande proporcao da variacao dos escores alcancados pelos alunos quando aspectos relativos a sala de aula sao considerados na modelagem.
Management of haemophilic patients with inhibitors in major orthopaedic surgery by immunadsorption, substitution of factor VIII and recombinant factor VIIa (NovoSeven®): a single centre experience

Summary. Inhibitors of factor VIII or FIX in haemophilic patients are a common and serious complication associated with an increased risk of life‐threatening bleeding during elective surgery. Substitution therapy fails to be effective, therefore an alternative treatment is needed. We have performed six major elective orthopaedic interventions in four patients with haemophilia A and inhibitors. A preoperative immunadsorbant therapy with TherasorbTM to eliminate inhibitors was successful in four cases, but during FVIII substitution inhibitors increased on day 4 to day 6 after surgery, leading to decreasing FVIII levels. Therefore, therapy was changed to recombinant FVIIa (rFVIIa; NovoSeven®). Two interventions had to be covered with sole rFVIIa therapy as immunadsorbant therapy failed to be effective in one case and the need for acute intervention did not allow pretreatment in the other. We did not see increased bleeding during or after surgery when compared to our experience with non‐inhibitor haemophilic patients. In conclusion, a preoperative decrease of inhibitors from immunadsorbant therapy, perioperative substitution of FVIII and changing treatment to rFVIIa when inhibitors are increased, is a safe and economic therapy for guaranteeing haemostasis in major elective orthopaedic surgery. On the contrary, sole therapy with rFVIIa allows immediate surgical intervention without a long hospital stay prior to surgery and a need for laboratory monitoring of inhibitor titres and FVIII levels. Our findings support data previously published.
1-[(4-Chlorobenzoyl)methyl]-4-(N,N-dimethylamino)pyridinium bromide sesquihydrate and 1-[(4-bromobenzoyl)methyl]-4-(N,N-dimethylamino)pyridinium bromide sesquihydrate.

The title compounds, C15H16ClN2O+. Br-. 1.5H2O and C15H16BrN2O+. Br-. 1.5H2O, are isomorphous. The benzene ring is oriented nearly normal to the pyridine ring in both compounds. The molecular packing is mainly influenced by intermolecular O-H.O and O-H.Br interactions, as well as weak intramolecular C-H.O interactions. The H2OBr- units form an extended water-bromide chain, with a bridging water molecule on a twofold axis.
EFFECTS OF METHOTREXATE AND LEFLUNOMIDE THERAPY ON KNEE SYNOVIUM OF ADJUVANT INDUCED ARTHRITIS AS A MODEL FOR RHEUMATOID ARTHRITIS

Objective: Leflunomide and methotrexate have proven to be efficacious in reducing joint inflammation and joint destruction in clinical models of arthritis and in rheumatoid arthritis. The objective of this study was to evaluate the effects of both drugs as well as their combination therapy on the synovium and cartilage of adjuvant arthritis as a model of rheumatoid arthritis (RA) in humans. Methodology: This study was carried out on forty animals stratified into 5 groups: normal, adjuvant arthritis (AA) control, AA who received leflunomide in a dose of 20 mg/kg orally, AA who received intraperitoneal methotrexate in a dose of 0.3 mg/kg twice weekly and AA who received both leflunomide and methotrexate of the same dose given in groups 3 and 4. All animals were sacrificed after 3 weeks; the right knee was dissected and examined with light microscopy. Oxidants markers [nitric oxide (NO) and malondialdhyde (MAD)] and antioxidants markers [glutathione (GSH), erythrocyte superoxide dismutase (SOD) and ceruloplasmin (CP)] were all measured. Results: All the treatment modalities showed variable degrees of improvement of synovial and cartilage scoring in comparison to AA (the non-treated group). The leflunomide treated group (group 3) showed the best improvement of Effect of Methotrexate & Leflunomide on Adjuvant Arthritis Manal Osman et al. 78 synovial pathology, while the combined therapy group (group 5) showed the best improvement of cartilage pathology. The oxidative stress markers showed some changes with different modalities of treatment where, nitric oxide did not change significantly between all groups. Malondialdhyde (MAD) was significantly lower in the methotrexate (MTX) treated group as compared to AA controls. Also, superoxide dismutase (SOD) was significantly lower in the leflunomide treated group, MTX treated group as well as in the group who received combined therapy as compared to AA the controls. Glutathione (GSH) level was significantly decreased with combination therapy as compared to the leflunomide treated group. Serum ceruloplasmin (CP) showed a significant decrease in its level in the MTX treated group as compared to the AA controls. MTX treatment (group 4) was the best in controlling oxidative stress markers. Conclusion: Further study is needed to evaluate the duration and dose effect of each drug on synovium, cartilage and oxidative markers.
Transparent and Flexible Resistive Random Access Memory Based on Al2O3 Film With Multilayer Electrodes

We report a transparent and flexible resistive random access memory (ReRAM) using a multi-thin-layer electrode. The transparent and flexible ReRAM includes a multi-thin-layer electrode that is transparent and flexible and an Al2O3 layer as a transparent oxide material. When the multi-thin-layer electrode is used for the top and bottom electrode for the ReRAM, the ReRAM has transparent and flexible properties. The stable memory operation uses a Ti layer and an MgO layer between the Al2O3 layer and multi-thin-layer electrodes. The transmittance of the ReRAM is over 70% at a visible wavelength on a PET substrate. We believe this transparent and flexible ReRAM will be useful for transparent and flexible electronic devices in the future.
Packed capillary reversed-phase liquid chromatography with high-performance electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry for proteomics.

In this study, high-efficiency packed capillary reversed-phase liquid chromatography (RPLC) coupled on-line with high-performance Fourier transform ion cyclotron resonance (FTICR) mass spectrometry has been investigated for the characterization of complex cellular proteolytic digests. Long capillary columns (80-cm) packed with small (3-micron) C18 bonded particles provided a total peak capacity of approximately 1000 for cellular proteolytic polypeptides when interfaced with an ESI-FTICR mass spectrometer under composition gradient conditions at a pressure of 10,000 psi. Large quantities of cellular proteolytic digests (e.g., 500 micrograms) could be loaded onto packed capillaries of 150-micron inner diameter without a significant loss of separation efficiency. Precolumns with suitable inner diameters were found useful for improving the elution reproducibility without a significant loss of separation quality. Porous particle packed capillaries were found to provide better results than those containing nonporous particles because of their higher sample capacity. Two-dimensional analyses from the combination of packed capillary RPLC with high-resolution FTICR yield a combined capacity for separations of > 1 million polypeptide components and simultaneously provided information for the identification of the separated components based upon the accurate mass tag concept previously described.
Baroreflex Activation Therapy Lowers Arterial Pressure Without Apparent Stimulation of the Carotid Bodies

Carotid baroreflex activation therapy produces a sustained fall in blood pressure in patients with resistant hypertension. Because the activation electrodes are implanted at the level of the carotid sinus, it is conceivable that the nearby located carotid body chemoreceptors are stimulated as well. Physiological stimulation of the carotid chemoreceptors not only stimulates respiration but also increases sympathetic activity, which may counteract the effects of baroreflex activation. The aim of this exploratory study is to investigate whether there is concomitant carotid chemoreflex activation during baroreflex activation therapy. Fifteen participants with the Rheos system were included in this single-center study. At arrival at the clinic, the device was switched off for 2 hours while patients were at rest. Subsequently, the device was switched on at 6 electric settings of high and low frequencies and amplitudes. Respiration and blood pressure measurements were performed during all device activation settings. Multilevel statistical models were adjusted for age, sex, body mass index, antihypertensive therapeutic index, sleep apnea, coronary artery disease, systolic blood pressure, and heart rate. There was no change in end-tidal carbon dioxide, partial pressure of carbon dioxide, breath duration, and breathing frequency during any of the electric settings with the device. Nevertheless, mean arterial pressure showed a highly significant decrease during electric activation (P<0.001). Carotid baroreflex activation therapy using the Rheos system did not stimulate respiration at several electric device activation energies, which suggests that there is no appreciable coactivation of carotid body chemoreceptors during device therapy.
Role of Sperm Sulfogalactosylglycerolipid in Mouse Sperm-Zona Pellucida Binding1

Abstract Sulfogalactosylglycerolipid (SGG) is the major sulfoglycolipid of mammalian male germ cells. Like other sulfoglycolipids, SGG is believed to be involved in cell-cell/extracellular matrix adhesion. Specifically, we investigated whether sperm SGG played a role in sperm-egg interaction. Initially, we produced an affinity-purified, rabbit polyclonal immunoglobulin (Ig) G antibody that specifically recognized SGG (anti-SGG). Indirect immunofluorescence using anti-SGG IgG localized SGG to the convex and concave ridges and the postacrosome of the mouse sperm head. Pretreatment of sperm with anti-SGG IgG/Fab inhibited sperm-zona pellucida (ZP) binding in vitro in a concentration-dependent manner (to a maximum of 62%). This inhibition was observed at the level of primary binding. Sperm treated with anti-SGG IgG underwent the spontaneous and ZP-induced acrosome reaction at the same rate as control sperm treated with preimmune rabbit serum IgG. Fluorescently labeled SGG liposomes were shown to associate specifically with the egg ZP, whereas fluorescently labeled liposomes of galactosylglycerolipid (SGG's parental lipid) and phosphatidylserine (negatively charged like SGG) did not. Furthermore, coincubation of SGG liposomes with sperm and isolated ZP inhibited sperm-ZP binding in a concentration-dependent manner. These results strongly suggest an involvement of sperm SGG in direct binding to the ZP.
A Periciliary Brush Promotes the Lung Health by Separating the Mucus Layer from Airway Epithelia

Sticky Mucus? Mucus—experienced, for example, in the form of a runny nose or productive cough—is one of the tools the body uses to expel or prevent the uptake of foreign matter. In a number of diseases, a failure of the normal mucus-control system leads to obstructions of the airways and respiratory problems. Button et al. (p. 937; see the Perspective by Dickey) examine the existing gel-on-liquid model, where the mucus is thought to sit on a watery periciliary layer around the beating lung cilia that has been used to explain the flow of mucus. A gel-on-brush model is proposed where the mucus sits on a brushlike periciliary layer. The key elements of this layer are membrane-tethered macromolecules that cause normal flow and clearance of mucus. When dehydrated, the interface is disrupted, preventing normal mucus motion. The lung is protected by a brushlike biopolymer that contributes to mucus flow and can trigger muco-obstructive diseases. Mucus clearance is the primary defense mechanism that protects airways from inhaled infectious and toxic agents. In the current gel-on-liquid mucus clearance model, a mucus gel is propelled on top of a “watery” periciliary layer surrounding the cilia. However, this model fails to explain the formation of a distinct mucus layer in health or why mucus clearance fails in disease. We propose a gel-on-brush model in which the periciliary layer is occupied by membrane-spanning mucins and mucopolysaccharides densely tethered to the airway surface. This brush prevents mucus penetration into the periciliary space and causes mucus to form a distinct layer. The relative osmotic moduli of the mucus and periciliary brush layers explain both the stability of mucus clearance in health and its failure in airway disease.
Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats

Background Dahl salt-sensitive (Dahl S) rats exhibit many phenotypic traits associated with salt-sensitive hypertension in man. Specifically, they are salt-sensitive, insulin-resistant and hyperlipidemic. They also develop endothelial dysfunction, cardiac injury and glomerulosclerosis. Insulin resistance is linked to hypertension, renal and cardiac damage and endothelial dysfunction. Thus, an agent that has diuretic action and can improve insulin resistance, like recombinant glucagon-like peptide-1(7-36)amide (rGLP-1), may have an antihypertensive effect. Objective To determine whether chronic administration of rGLP-1 attenuates the development of hypertension, endothelial dysfunction and/or hypertension-induced renal and cardiac end organ damage in Dahl S rats. Methods Mean arterial pressure (MAP) and urinary excretion of protein and albumin were measured in Dahl S rats before and after they were fed a 8% NaCl diet and infused with rGLP-1 (1 μg/kg per min, i.v.) or vehicle for 14 days. At the end of the study, the degree of renal and cardiac injury was histologically assessed and endothelium-dependent relaxing function was studied using aortic rings. In other rats, the effects of rGLP-1 on sodium and water balance and plasma glucose and insulin levels for the first 3 days following a step change in sodium intake from a 0.1% NaCl diet to 7.5 mEq/day were determined. Results rGLP-1 significantly attenuated the development of hypertension in Dahl S rats (136 ± 7 versus 174 ± 6 mmHg). This was associated with reduction in proteinuria (46 ± 7 versus 128 ± 15 mg/day) and albuminuria (46 ± 7 versus 86 ± 18 mg/day) and improvement of endothelial function and renal and cardiac damage. rGLP-1 markedly increased urine flow and sodium excretion for the first 3 days following elevation in sodium intake. It had no significant effects on plasma glucose and insulin concentrations. Conclusion rGLP-1 has antihypertensive and cardiac and renoprotective effects in Dahl S rats fed a high salt diet. The antihypertensive effect of rGLP-1 in Dahl S rats is due mainly to its diuretic and natriuretic effects, rather than an effect to improve insulin-resistance.