Miracle-dz/UniFAR-FTUs huggingface dataset:
Adsorption behavior of a human monoclonal antibody at hydrophilic and hydrophobic surfaces

One aspiration for the formulation of human monoclonal antibodies (mAb) is to reach high solution concentrations without compromising stability. Protein surface activity leading to instability is well known, but our understanding of mAb adsorption to the solid-liquid interface in relevant pH and surfactant conditions is incomplete. To investigate these conditions, we used total internal reflection fluorescence (TIRF) and neutron reflectometry (NR). The mAb tested (“mAb-1”) showed highest surface loading to silica at pH 7.4 (~12 mg/m2), with lower surface loading at pH 5.5 (~5.5 mg/m2, further from its pI of 8.99) and to hydrophobized silica (~2 mg/m2). The extent of desorption of mAb-1 from silica or hydrophobized silica was related to the relative affinity of polysorbate 20 or 80 for the same surface. mAb-1 adsorbed to silica on co-injection with polysorbate (above its critical micelle concentration) and also to silica pre-coated with polysorbate. A bilayer model was developed from NR data for mAb-1 at concentrations of 50–5000 mg/L, pH 5.5, and 50–2000 mg/L, pH 7.4. The inner mAb-1 layer was adsorbed to the SiO2 surface at near saturation with an end-on” orientation, while the outer mAb-1 layer was sparse and molecules had a “side-on” orientation. A non-uniform triple layer was observed at 5000 mg/L, pH 7.4, suggesting mAb-1 adsorbed to the SiO2 surface as oligomers at this concentration and pH. mAb-1 adsorbed as a sparse monolayer to hydrophobized silica, with a layer thickness increasing with bulk concentration - suggesting a near end-on orientation without observable relaxation-unfolding.
Pharmacotherapy Review: Angiotensin Receptor Antagonists

Angiotensin receptor blockers are one of several drug classes that act by interfering with activity of the renin‐angiotensin axis. Drugs in this class are as effective as angiotensin‐converting enzyme inhibitors in the reduction of blood pressure in hypertensive patients. Results from a series of outcomes trials increasingly support the use of drugs in this class as cardioprotective and renoprotective agents in patients with heart failure, diabetic nephropathy, and post‐myocardial infarction.
An Optimization Approach for Well-Targeted Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique which modifies neural excitability by providing weak currents through scalp electrodes. The aim of this study is to introduce and analyze a novel optimization method for safe and well-targeted multiarray tDCS. For optimization, we consider an optimal control problem for a Laplace equation with Neumann boundary conditions with control and pointwise gradient state constraints. We prove well-posedness results for the proposed methods and provide computer simulation results in a highly realistic six-compartment geometry-adapted hexahedral head model. For discretization of the proposed minimization problem the finite element method is employed and the existence of at least one minimizer to the discretized optimization problem is shown. For numerical solution of the corresponding discretized problem we employ the alternating direction method of multipliers and comprehensively examine the cortical current flow field with regard to focality, target intensity, and orientation. The numerical results reveal that the optimized current flow fields show significantly higher focality and, in most cases, higher directional agreement to the target vector in comparison to standard bipolar electrode montages.
In Vitro Activities of BAL9141, a Novel Broad-Spectrum Pyrrolidinone Cephalosporin, against Gram-Negative Nonfermenters

ABSTRACT The activities of BAL9141 (formerly Ro 63-9141), a novel pyrrolidinone-3-ylidenemethyl cephalosporin, against 244 strains of gram-negative nonfermenters were evaluated. The overall MIC at which 50% of isolates are inhibited (MIC50) and the overall MIC90 were 2 and 64 μg/ml, respectively, which are similar to those of imipenem, lower than those of the other cephalosporins tested, amoxicillin, and the ticarcillin-clavulanic acid combination, and much higher than those of ciprofloxacin. BAL9141 shows species-dependent activity in vitro against a variety of gram-negative nonfermentative pathogens.
1 Energy-Efficient Big Data Analytics in Datacenters

­The volume of generated data increases by the rapid growth of Internet of Things (IoT), leading to the big data proliferation and more opportunities for data centers. Highly virtualized cloud-based datacenters are currently considered for big data analytics. However big data requires datacenters with promoted infrastructure capable of undertaking more responsibilities for handling and analyzing data. Also, as the scale of the datacenter is increasingly expanding, minimizing energy consumption and operational cost is a vital concern. Future datacenters infrastructure including interconnection network, storage and servers should be able to handle big data applications in an energy-efficient way. In this chapter, we aim to explore different aspects of could-based datacenters for big data analytics. First the datacenter architecture including computing and networking technologies as well as data centers for cloud-based services will be illustrated. Then the concept of big data, cloud computing and some of the existing cloud-based datacenter platforms including tools for big data analytics will be introduced. We later discuss the techniques for improving energy efficiency in the cloud-based datacenters for big data analytics. Finally, the current and future trends for datacenters in particular with respect to energy consumption to support big data analytics will be discussed.
Noun bias in maternal speech to one-year-olds

ABSTRACT This study examines the distribution of nouns and verbs in maternal speech to one-year-olds. Mothers and children were videotaped during toy play and non-toy play. Nouns and verbs in maternal speech were coded for frequency, sentence position and occurrence with grammatical inflections. maternal speech was also coded for utterances that prompted the child to produce a noun or a verb. Frequency of nouns and verbs varied with context. There were more noun types and tokens during toy play, and more verb types and tokens during non-toy play. Nouns occurred more often than verbs in shorter maternal sentences, in sentence-final position, and with fewer grammatical inflections. Mothers also more often prompted their children to produce nouns. There was a significant positive correlation between frequency of noun types and tokens during toy play, and the proportion of nouns in children's first 50 words.
NCX4016 (NO-aspirin) inhibits thromboxane biosynthesis and tissue factor expression and activity in human monocytes.

BACKGROUND NCX4016 (2 acetoxy-benzoate 2-(2-nitroxymethyl)-phenyl ester, NicOx S.A. , France) is an antithrombotic agent chemically related to acetylsalicylic acid (ASA). We hypothesised that NCX4016, being able to release nitric oxide (NO) and to inhibit cyclo-oxygenase, might inhibit the prothrombotic function in human monocytes. MATERIAL AND METHODS The effects of NCX4016 and ASA on the release of thromboxane (TX) B2 and tissue factor expression and activity were compared using adherent human monocytes. The tested drugs were added before stimulation with 10 Kg/ml LPS and incubation lasted 6 hours. TXB2 concentration was measured by RIA in the supernatant of cultured cells. Immunoreactive tissue factor (TF) concentration was determined by enzyme-linked immunoassay and TF activity was assayed by measuring the peptidyl activity of the tissue factor/ factor VII complex. RESULTS Both ASA and NCX4016 10-300 Kmol/L dose-dependently reduced TXB2 release. NCX4016 activity was comparable to that of equimolar ASA. Part of the activity of NCX4016 up to 100 Kmol/L was prevented by 10 Kml/L ODQ, inhibitor of cGMP generation. Immunoreactive TF was dose-dependently inhibited by 300 Kmol/L NCX4016, but not by ASA. Also tissue TF activity was reduced by 300 Kmol/L NCX4016, but not by ASA. CONCLUSIONS The present results indicate that NCX4016 not only has anti-platelet effects but also inhibits prothrombotic activities in human monocytes, partly via NO-dependent mechanisms. NCX4016 may prove effective in the clinical setting of athero-thrombosis.
The Global Expansion of Precarious Employment, Work Disorganization, and Consequences for Occupational Health: A Review of Recent Research

In this review of a range of studies on the health and safety effects of precarious employment in industrialized societies published since 1984, the authors examine the overall findings and methodological issues and identify areas in need of further research. Of the 93 published journal articles and monographs/book chapters reviewed, 76 studies found precarious employment was associated with a deterioration in occupational health and safety (OHS) in terms of injury rates, disease risk, hazard exposures, or worker (and manager) knowledge of OHS and regulatory responsibilities. Of the more than 25 studies each on outsourcing and organizational restructuring/downsizing, well over 90 percent find a negative association with OHS. The evidence is fairly persuasive for temporary workers, with 14 of 24 studies finding a negative association with OHS. The evidence is less strong for small business, and a handful of studies on part-time workers found no clear association with negative OHS outcomes (in some cases the reverse). Further research is needed to more clearly link health effects to particular business practices and neoliberal policies and to explore the regulatory implications of the growth of precarious employment. The authors suggest some ways to conceptualize the association between precarious employment and occupational health.
Long-term outcomes and prognostic factors in 78 Japanese patients with advanced pancreatic neuroendocrine neoplasms: a single-center retrospective study.

OBJECTIVE Despite an increase in the number of Japanese patients with pancreatic neuroendocrine neoplasms, long-term outcomes and prognostic factors, especially for those with advanced disease, remain unclear. METHODS We retrospectively reviewed the medical records of 78 patients with unresectable pancreatic neuroendocrine neoplasms treated at our hospital from January 1987 to March 2015. Survival analyses were performed using Kaplan-Meier methods. Prognostic significance of several clinicopathological factors were analyzed by univariate and multivariate analyses using a Cox regression model. RESULTS Median overall survivals of pancreatic neuroendocrine tumor (n = 64) and pancreatic neuroendocrine carcinoma (n = 14) were 83.7 and 9.1 months, respectively (hazard ratio: 0.02, 95% confidence interval: 0.01-0.08, P < 0.001). Although no significant differences were observed using a Ki-67 cut-off value of 2% (hazard ratio: 0.46, 95% confidence interval: 0.16-1.13, P = 0.0989), a Ki-67 cut-off of 10% was a significant predictor in patients with pancreatic neuroendocrine tumor (hazard ratio: 9.95, 95% confidence interval, 3.01-32.97, P < 0.001). Treatment after the advent of targeted therapy (hazard ratio: 0.07, 95% confidence interval: 0.03-0.19, P < 0.001) and the presence of bone metastases (hazard ratio: 4.38, 95% confidence interval: 1.42-11.29, P = 0.013) were significant prognostic factors in patients with pancreatic neuroendocrine tumor evaluated by univariate analysis. Multivariate analysis also revealed that a Ki-67 index ≥10% (hazard ratio: 38.8, 95% confidence interval: 8.42-226.62, P < 0.001), approval of targeted therapy (hazard ratio: 0.02, 95% confidence interval: 0.00-0.11, P < 0.001) and bone metastases (hazard ratio: 5.56, 95% confidence interval: 1.10-24.00, P = 0.039) were independent prognostic factors. CONCLUSIONS We elucidated the long-term outcomes and prognostic factors in Japanese patients with advanced pancreatic neuroendocrine neoplasms.
Overview of Regular Dialysis Treatment in Japan (as of 31 December 2011)

A nationwide statistical survey of 4255 dialysis facilities was conducted at the end of 2011. Responses were submitted by 4213 facilities (99.0%). The number of new patients started on dialysis was 38 613 in 2011. Although the number of new patients decreased in 2009 and 2010, it increased in 2011. The number of patients who died each year has been increasing; it was 30 743 in 2011, which exceeded 30 000 for the first time. The number of patients undergoing dialysis has also been increasing every year; it was 304 856 at the end of 2011, which exceeded 300 000 for the first time. The number of dialysis patients per million at the end of 2011 was 2385.4. The crude death rate of dialysis patients in 2011 was 10.2%, which exceeded 10% for the first time in the last 20 years. The mean age of new dialysis patients was 67.84 years and the mean age of the entire dialysis patient population was 66.55 years. The most common primary cause of renal failure among new dialysis patients was diabetic nephropathy (44.3%). Diabetic nephropathy was also the most common primary disease among the entire dialysis patient population (36.7%), exceeding chronic glomerulonephritis (34.8%) which had been the highest until last year. The survey included questions related to the Great East Japan Earthquake, which occurred on 11 March 2011. The results on items associated with the Great East Japan Earthquake were reported separately from this report. The mean uric acid levels of the male and female patients were 7.30 and 7.19 mg/dL, respectively. Certain drugs for hyperuricemia were prescribed for approximately 17% of patients. From the results of the facility survey, the number of patients who underwent peritoneal dialysis (PD) was 9642 and the number of patients who did not undergo PD despite having a peritoneal dialysis catheter was 369. A basic summary of the results on the survey items associated with PD is included in this report and the details were reported separately.
Rapamycin enhances chemotherapy‐induced cytotoxicity by inhibiting the expressions of TS and ERK in gastric cancer cells

We have previously reported the synergistic cytotoxic effects of Docetaxel (TXT) and S‐1 in gastric cancer in vitro and in vivo, and the combination regimen is now under phase III clinical trail. In this study, to elucidate whether the rapamycin, the inhibitor of the mTOR (mammalian target of rapamaycin), can enhance the potentiation of TXT and 5‐fluorouracil (5‐Fu) in gastric carcinoma cells. Rapamycin inhibited the growth of TMK‐1, MKN‐28, MKN‐45 and MKN‐74 cell lines by MTT assay, and it demonstrated the cytostatic effects as G1 arrest shown by flowcytometry. However, the cytotoxic effects of 5‐Fu, TXT and cisplatin were enhanced by 2 to 4 times with the concomitant administration of rapamycin. To clarify the mechanism of the potentiation, the expression changes of the enzymes relating DNA metabolism and cell growth signal transduction pathways were examined by western blot analysis. Interestingly, the expression of thymidilate synthase was markedly decreased by the administration of rapamycin in TMK‐1 cells in a time‐ and dose‐dependent manner. Moreover, rapamycin decreased the phosphorylation of 4E‐BP1, the phosphorylation of ERK1/2 and enhanced the phosphorylation of c‐Jun NH2‐terminal kinase, and the activation of caspase of apoptotic pathways in combination with TXT. These results strongly indicate that the mTOR inhibitor can enhance the potentiation of TXT and 5‐Fu or S‐1 and can serve as a new therapeutic tool for advanced and recurrent gastric cancer patients.
Arginine vasopressin, but not epinephrine, improves survival in uncontrolled hemorrhagic shock after liver trauma in pigs*

ObjectiveEpinephrine is widely used for treatment of life-threatening hypotension, although new vasopressor drugs may merit evaluation. The purpose of this study was to determine the effects of vasopressin vs. epinephrine vs. saline placebo on hemodynamic variables, regional blood flow, and short-term survival in an animal model of uncontrolled hemorrhagic shock and delayed fluid resuscitation. DesignProspective, randomized, laboratory investigation that used a porcine model for measurement of hemodynamic variables and regional abdominal organ blood flow. SettingUniversity hospital laboratory. SubjectsA total of 21 pigs weighing 32 ± 3 kg. InterventionsThe anesthetized pigs were subjected to a penetrating liver injury, which resulted in a mean ± sem loss of 40% ± 5% of estimated whole blood volume within 30 mins and mean arterial pressures of <20 mm Hg. When heart rate declined progressively, pigs randomly received a bolus dose and continuous infusion of either vasopressin (0.4 units/kg and 0.04 units·kg−1·min−1, n = 7), or epinephrine (45 &mgr;g/kg and 5 &mgr;g·kg−1·min−1, n = 7), or an equal volume of saline placebo (n = 7), respectively. At 30 mins after drug administration, all surviving animals were fluid resuscitated while bleeding was surgically controlled. Measurements and Main ResultsMean ± sem arterial blood pressure at 2.5 and 10 mins was significantly (p < .001) higher after vasopressin vs. epinephrine vs. saline placebo (82 ± 14 vs. 23 ± 4 vs. 11 ± 3 mm Hg, and 42 ± 4 vs. 10 ± 5 vs. 6 ± 3 mm Hg, respectively). Although portal vein blood flow was temporarily impaired by vasopressin, it was subsequently restored and significantly (p < .01) higher when compared with epinephrine or saline placebo (9 ± 5 vs. 121 ± 3 vs. 54 ± 22 mL/min and 150 ± 20 vs. 31 ± 17 vs. 0 ± 0 mL/min, respectively). Hepatic and renal artery blood flow was significantly higher throughout the study in the vasopressin group; however, no further bleeding was observed. Despite a second bolus dose, all epinephrine- and saline placebo–treated animals died within 15 mins after drug administration. By contrast, seven of seven vasopressin-treated animals survived until fluid replacement, and 60 mins thereafter, without further vasopressor therapy (p < .01). Moreover, blood flow to liver, gut, and kidney returned to normal values in the postshock phase. ConclusionsVasopressin, but not epinephrine or saline placebo, improved short-term survival in a porcine model of uncontrolled hemorrhagic shock after liver injury when surgical intervention and fluid replacement was delayed.
CD81/CD9 tetraspanins aid plasmacytoid dendritic cells in recognition of hepatitis C virus–infected cells and induction of interferon‐alpha

Recognition of hepatitis C virus (HCV)‐infected hepatocyes and interferon (IFN) induction are critical in antiviral immune response. We hypothesized that cell‐cell contact between plasmacytoid dendritic cells (pDCs) and HCV‐infected cells was required for IFN‐α induction through the involvement of cell‐surface molecules. Coculture of human peripheral blood mononuclear cells (PBMCs) with genotype 1a full‐length (FL) HCV genomic replicon cells or genotype 2a Japanese fulminant hepatitis type 1 (JFH‐1) virus‐infected hepatoma cells (JFH‐1), and not with uninfected hepatoma cells (Huh7.5), induced IFN‐α production. Depletion of pDCs from PBMCs attenuated IFN‐α release, and purified pDCs produced high levels of IFN‐α after coculture with FL replicons or JFH‐1‐infected cells. IFN‐α induction by HCV‐containing hepatoma cells required viral replication, direct cell‐cell contact with pDCs, and receptor‐mediated endocytosis. We determined that the tetraspanin proteins, CD81 and CD9, and not other HCV entry receptors, were required for IFN‐α induction in pDCs by HCV‐infected hepatoma cells. Disruption of cholesterol‐rich membrane microdomains, the localization site of CD81, or inhibition of the CD81 downstream molecule, Rac GTPase, inhibited IFN‐α production. IFN‐α induction involved HCV RNA and Toll‐like receptor (TLR) 7. IFN‐α production by HCV‐infected hepatoma cells was decreased in pDCs from HCV‐infected patients, compared to healthy controls. We found that preexposure of healthy PBMCs to HCV viral particles attenuated IFN‐α induction by HCV‐infected hepatoma cells or TLR ligands, and this inhibitory effect could be prevented by an anti‐HCV envelope glycoprotein 2–blocking antibody. Conclusion: Our novel data show that recognition of HCV‐infected hepatoma cells by pDCs involves CD81‐ and CD9‐associated membrane microdomains and induces potent IFN‐α production. (HEPATOLOGY 2013;58:940–949)
Determination of Apolipoprotein(a) Isoforms and Lipoprotein(a) in Children with Diabetes Mellitus Type 1

Lipoprotein(a) is composed of apoB–100 and the unique protein apolipoprotein(a). Plasma levels of Lipoprotein(a) are determined largely by variation in the gene that encodes it. High plasma levels and small-sized apolipoprotein(a) isoforms are thought to be an independent risk factor for development of atherosclerosis. Children with diabetes mellitus are prone to early development of atherosclerosis. We investigated apolipoprotein(a) polymorphisms and lipoprotein(a) plasma concentrations in 60 normoalbuminuric children with diabetes mellitus type 1 and in 100 healthy children aged between 9 and 17 years. Sodium dodecyl sulphate polyacrylamide gel electrophoresis was used for separation of apolipoprotein(a) isoforms. Individuals expressed a single band (homozygotic), a double band (heterozygotic) or no band (null phenotype). In both groups single-banded phenotypes were more common than double-banded phenotypes: 50.0 % vs. 46.7 % for patients and 53.0 % vs. 43.0 % for controls. A higher prevalence of large size (≥22 Kringle IV repeats) apolipoprotein(a) isoforms, associated with lower lipoprotein(a) concentrations, was detected in the patients and in the controls. Most plasma lipoprotein(a) levels were in the low range. Lipoprotein(a) concentrations below the risk limit of 30 mg/dL were present in 90 % of subjects. The comparison of the two groups showed no significant difference between their mean and median plasma concentration of lipoprotein(a).
An embedded device technology based on a molded reconfigured wafer

We report an innovative embedded device wafer level packaging technology based on a "molded reconfigured 200 mm wafer". Silicon dice are tested, grinded, and diced. For the set-up of the "reconfigured wafer" these bare silicon dice are placed faces down onto a carrier system. The core process of this technology is the encapsulation of silicon dice. We demonstrate that compression molding is a promising approach with respect to robust processing, topology, adhesion, and reliability properties. The "molded reconfigured wafer" is the base to apply thin-film interconnects similar to back-end of line processes
SUCESSÃO EMPRESARIAL: A PREPARAÇÃO DO SUCESSOR PARA O PROCESSO SUCESSÓRIO NAS EMPRESAS FAMILIARES DE MONTE CARMELO – MG

A empresa familiar desempenha um papel de destaque na esfera economica e social. No entanto, apesar de sua importância, as empresas familiares tendem a ter uma expectativa de vida menor que as nao-familiares ou menos familiares. A perpetuacao em uma empresa e normalmente bem-sucedida se a sucessao for bem planejada e, para que uma sucessao seja realizada com sucesso e necessario, alem de planejar e executar o plano com eficacia, realizar a preparacao dos sucessores. Nesse sentido, esta pesquisa analisou o processo sucessorio em empresas familiares de Monte Carmelo – MG, para verificar se a preparacao do sucessor e um processo estruturado ou informal e se a sucessao foi de forma espontânea ou por forca da posicao hereditaria, alem de verificar a trajetoria do sucessor na empresa. Foi utilizado nesta pesquisa um questionario com questoes de multipla escolha em uma amostra de empresas que possuem historico de sucessao no municipio. Este trabalho se justifica pela relevância das empresas familiares e o numero que elas representam de empregabilidade no Brasil. A importância deste estudo se da pelo fato de buscar entender como funciona o processo sucessorio e a preparacao dos sucessores em empresas familiares do municipio de Monte Carmelo – MG. PALAVRAS-CHAVE: Empresa familiar; Gestao; Sucessao.