Miracle-dz/UniFAR-FTUs huggingface dataset:
XMetA, an allosteric monoclonal antibody to the insulin receptor, improves glycaemic control in mice with diet‐induced obesity

XMetA, a high‐affinity, fully human monoclonal antibody, allosterically binds to and activates the insulin receptor (INSR). Previously, we found that XMetA normalized fasting glucose and glucose tolerance in insulinopenic mice. To determine whether XMetA is also beneficial for reducing hyperglycaemia due to the insulin resistance of obesity, we have now evaluated XMetA in hyperinsulinemic mice with diet‐induced obesity. XMetA treatment of these mice normalized fasting glucose for 4 weeks without contributing to weight gain. XMetA also corrected glucose tolerance and improved non‐high density lipoprotein cholesterol. These studies indicate, therefore, that monoclonal antibodies that allosterically activate the INSR, such as XMetA, have the potential to be novel agents for the treatment of hyperglycaemia in conditions associated with the insulin resistance of obesity.
Multichannel Dynamic-Range Compression Using Digital Frequency Warping

A multichannel dynamic-range compressor system using digital frequency warping is described. A frequency-warped filter is realized by replacing the filter unit delays with all-pass filters. The appropriate design of the frequency warping gives a nonuniform frequency representation very close to the auditory Bark scale. The warped compressor is shown to have substantially reduced group delay in comparison with a conventional design having comparable frequency resolution. The warped compressor, however, has more delay at low than at high frequencies, which can lead to perceptible changes in the signal. The detection threshold for the compressor group delay was determined as a function of the number of all-pass filter sections in cascade needed for a detectible change in signal quality. The test signals included clicks, vowels, and speech, and results are presented for both normal-hearing and hearing-impaired subjects. Thresholds for clicks are lower than thresholds for vowels, and hearing-impaired subjects have higher thresholds than normal-hearing listeners. A frequency-warped compressor using a cascade of 31 all-pass filter sections offers a combination of low overall delay, good frequency resolution, and imperceptible frequency-dependent delay effects for most listening conditions.
miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of Macrophages

The Notch pathway plays critical roles in the differentiation and polarized activation of macrophages; however, the downstream molecular mechanisms underlying Notch activity in macrophages remain elusive. Our previous study has identified a group of microRNAs that mediate Notch signaling to regulate macrophage activation and tumor-associated macrophages (TAMs). In this study, we demonstrated that miR-148a-3p functions as a novel downstream molecule of Notch signaling to promote the differentiation of monocytes into macrophages in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF). Meanwhile, miR-148a-3p promoted M1 and inhibited M2 polarization of macrophages upon Notch activation. Macrophages overexpressing miR-148a-3p exhibited enhanced ability to engulf and kill bacteria, which was mediated by excessive production of reactive oxygen species (ROS). Further studies using reporter assay and Western blotting identified Pten as a direct target gene of miR-148a-3p in macrophages. Macrophages overexpressing miR-148a-3p increased their ROS production through the PTEN/AKT pathway, likely to defend against bacterial invasion. Moreover, miR-148a-3p also enhanced M1 macrophage polarization and pro-inflammatory responses through PTEN/AKT-mediated upregulation of NF-κB signaling. In summary, our data establish a novel molecular mechanism by which Notch signaling promotes monocyte differentiation and M1 macrophage activation through miR-148a-3p, and suggest that miR-148a-3p-modified monocytes or macrophages are potential new tools for the treatment of inflammation-related diseases.
Parameter estimation by implicit sampling

Author(s): Morzfeld, M; Tu, X; Wilkening, J; Chorin, AJ | Abstract: © 2015 Mathematical Sciences Publishers. Implicit sampling is a weighted sampling method that is used in data assimilation to sequentially update state estimates of a stochastic model based on noisy and incomplete data. Here we apply implicit sampling to sample the posterior probability density of parameter estimation problems. The posterior probability combines prior information about the parameter with information from a numerical model, e.g., a partial differential equation (PDE), and noisy data. The result of our computations are parameters that lead to simulations that are compatible with the data. We demonstrate the usefulness of our implicit sampling algorithm with an example from subsurface flow. For an efficient implementation, we make use of multiple grids, BFGS optimization coupled to adjoint equations, and Karhunen-Loeve expansions for dimensional reduction. Several difficulties of Markov chain Monte Carlo methods, e.g., estimation of burn-in times or correlations among the samples, are avoided because the implicit samples are independent.
Diffuse retinal pigment epitheliopathy complicating systemic corticosteroid treatment.

AIMS/BACKGROUND--This study was undertaken to confirm the association between diffuse retinal pigment epitheliopathy (DRPE) and systemic corticosteroid therapy. This finding can be of help in determining an aetiological factor in DRPE and associated diseases. Corticosteroids may contribute to the development of leakage in the presence of a retinal pigment epitheliopathy or central serous chorioretinopathy. METHODS--Cases of DRPE were collected from the files of members of the European Fluorescein Angiography Club. There were 34 who developed their ophthalmic symptoms while being treated with corticosteroids. RESULTS--DRPE developed in 34 patients from 10 European eye clinics during systemic treatment with corticosteroids. Thirteen patients were treated with corticosteroids after allotransplantation, 21 other patients developed ocular symptoms while treated with steroids for serious systemic disorders. Symptoms occurred in some patients when the daily corticosteroid dosage was elevated, and the visual complaints ameliorated or even disappeared sometimes on discontinuation of the corticosteroid therapy. CONCLUSION--Corticosteroids can damage the retinal pigment epithelial barrier and predispose a patient to serous retinal detachment, whereas psychological stress may play a role in the development of central serous chorioretinopathy. A decrease of the daily corticosteroid dosage may help to diminish the visual symptoms.
Improving load forecast accuracy by clustering consumers using smart meter data

Utility companies provide electricity to a large number of consumers. These companies need to have an accurate forecast of the next day electricity demand. Any forecast errors will result in either reliability issues or increased costs for the company. Because of the widespread roll-out of smart meters, a large amount of high resolution consumption data is now accessible which was not available in the past. This new data can be used to improve the load forecast and as a result increase the reliability and decrease the expenses of electricity providers. In this paper, a number of methods for improving load forecast using smart meter data are discussed. In these methods, consumers are first divided into a number of clusters. Then a neural network is trained for each cluster and forecasts of these networks are added together in order to form the prediction for the aggregated load. In this paper, it is demonstrated that clustering increases the forecast accuracy significantly. Criteria used for grouping consumers play an important role in this process. In this work, three different feature selection methods for clustering consumers are explained and the effect of feature extraction methods on forecast error is investigated.
Effects of Dietary Levels of Calcium and Nonphytate Phosphorus in Broiler Starter Diets on Total and Water-Soluble Phosphorus Excretion as Influenced by Phytase and Addition of 25-Hydroxycholecalciferol 1

A st udy was conducted utilizing a 2 x 2 x 4 x 4 factorial arrangements in which a nutritionall y adequate diet was fed with and without 1200 FTU/kg of phytase and with or without 69 µg/kg of 25 - hydroxycholecalciferol, four levels of nonphytate phosphorus (NPP) (0.35, 0.40, 0.45, and 0.50%) and four levels of calcium (2:1 Ca:NPP ratio, 0.2% Ca less than the 2:1 ratio, 0.2% Ca more than the 2:1 ratio, and 0.4% Ca more than the 2:1 ratio) for a total of 64 treatments, each fed to two replicate pens of five male broilers in wire-floored battery brooders. At 14 d of age excreta samples were collected, frozen, freeze dried, and analyzed for total P (TP), Ca, and water-soluble P (WSP). The ratio of WSP/TP was calculated from these data. The TP, Ca and WSP in excreta increased as the NPP content of the diet increased. Phytase supplementation reduced TP and Ca but increased WSP concentration and the WSP/TP ratio; this effect might be reversed if levels of NPP lower than those evaluated in the present study are utilized to account for the improvement on phytate phosphorus digestion. The addition of Hy-D reduced TP and Ca concentration in broiler excreta. The most remarkable effect was seen by increasing dietary calcium levels above the 2:1 Ca:NPP ratio typically used in the poultry industry. As the dietary Ca increased, there were significantly reduced excreta levels of TP, WSP and the WSP/TP ratio was significantly reduced. Compared to chicks fed diets with the 2:1 Ca:NPP ratio, the WSP in excreta was reduced 40% by adding 0.20% more Ca and 54% by adding 0.40% more Ca. As the WSP fraction of broiler litter is the primary concern in eutrophicatio n, increasing the dietary Ca level in conjunction with feeding closer to the P requirement should be a cost- effective means of combating the adverse effects of broiler litter on pastures.
Foetal Haemoglobin, Erythrocytes Containing Foetal Haemoglobin, and Hematological Features in Congolese Patients with Sickle Cell Anaemia

High HbF levels and F cells are correlated with reduced morbidity and mortality in sickle cell disease (SCD). This paper was designed to determine the HbF and F cells levels in Congolese sickle cell anemia (SCA) patients in order to determine their impact on the expression of SCD. Population and Method. HbF levels were measured in 89 SCA patients (mean age 11.4 yrs) using a standard HPLC method. F cell quantitation was done in a second group of SCA patients (n = 42, mean age 8.9 yrs) and compared with a control group (n = 47, mean age 5 yrs). F cells were quantified by a cytofluorometric system (MoAb-HbF—FITC; cut off at 0.5%). Results. The mean value of HbF was 7.2% ± 5.0 with heterogeneous distribution, most patients (76%) having HbF < 8%. Mean values of F-cells in SCA patients and control group were 5.4% ± 7.6 (median: 2.19%; range 0,0–30,3%) and 0.5% ± 1.6 (median 0.0, range 0–5.18), respectively. SCA patients with F cells >4.5% developed less painful crisis and had higher percentage of reticulocytes. Conclusion. Congolese SCA patients displayed low levels of HbF and F-cells that contribute to the severity of SCD.
Value, Price Consciousness, and Consumption Frugality

Abstract Recently, Lastovicka, Bettencourt, Hughner, and Kuntze (1999) studied consumer frugality and argued that frugal consumers tend to be less impulsive and more disciplined in how they spend money, compared to other consumers. The frugal are also resourceful users and re-users of products and tend to be more independent than other consumers are. Lastovicka et al. (1999) summarized by showing that frugality is a useful concept for consumer behavior studies. This study examines frugality's relationships with price and value consciousness. Additionally, its impact on actual consumption is examined. Data from Israeli consumers mostly supports the study's hypotheses. The research and managerial implications of the findings are discussed.
Clarification of risk factors for hepatectomy in patients with hepatocellular carcinoma.

BACKGROUND/AIMS Hepatic resection is still associated with a higher morbidity than other major abdominal surgery. The aim of this study was to define risk factors for postoperative morbidity, and to evaluate the plasma cytokine pattern to detect early postoperative infection in patients with hepatocellular carcinoma. METHODOLOGY One hundred and thirty-nine hepatic resections for hepatocellular carcinoma over a 10-year period from 1987 to 1997 were performed. Preoperative and intraoperative predictors of morbid outcomes were analyzed using multiple regression in a stepwise, logistic model. The postoperative concentrations of interleukin-6, interleukin-8, granulocytecolony stimulating factor, endotoxin and hepatocyte growth factor were measured in 32 patients following hepatic resection. RESULTS Mortality rate within 30 postoperative days was 2.2%, with morbidity occurring in 40.2%. Significant pre- and intraoperative predictors for morbidity were ICGR15 and the presence of liver cirrhosis. Changes of interleukin-6, interleukin-8, granulocytecolony stimulating factor and endotoxin levels were not consistent with the occurrence of postoperative complications. However, the postoperative peak hepatocyte growth factor levels were positively correlated with morbidity. CONCLUSIONS ICGR15 and presence of liver cirrhosis had a marked effect on the incidence of postoperative complications after hepatectomy for hepatocellular carcinoma. An increase of serum hepatocyte growth factor level could be used to detect complications in the early postoperative period, but the inflammatory cytokine response after hepatectomy did not relate to an increased complication rate.
Survey of Consistent Network Updates

Computer networks have become a critical infrastructure. Designing dependable computer networks however is challenging, as such networks should not only meet strict requirements in terms of correctness, availability, and performance, but they should also be flexible enough to support fast updates, e.g., due to a change in the security policy, an increasing traffic demand, or a failure. The advent of Software-Defined Networks (SDNs) promises to provide such flexiblities, allowing to update networks in a fine-grained manner, also enabling a more online traffic engineering. In this paper, we present a structured survey of mechanisms and protocols to update computer networks in a fast and consistent manner. In particular, we identify and discuss the different desirable update consistency properties a network should provide, the algorithmic techniques which are needed to meet these consistency properties, their implications on the speed and costs at which updates can be performed. We also discuss the relationship of consistent network update problems to classic algorithmic optimization problems. While our survey is mainly motivated by the advent of Software-Defined Networks (SDNs), the fundamental underlying problems are not new, and we also provide a historical perspective of the subject.
Kemampuan Mahasiswa Berkomunikasi Lisan Melalui Proses Belajar Mengajar

Basically improvement effort of competency and lecturer professionality becoming main attention of Higher Education Directorate General (Ditjen DIKTI). This thing based on conception that lecturer is one of a real important component in learning process, and directly influences improvement of quality of learning process for student. In working professionally, faculty of economics graduate hardly requires ability to oral communication. This research purpose to analyze ability of learning process in the effort increasing ability to oral communication of students. Ability to oral communication will be proxy without existence of fear in communicating. Base on research purpose, primary data applied in this research. Research population are junior students on academic year 2006/2007 and senior students which has gone through more than 120 sks. Both consist of economic development, economic management, & economic accountancy study program. The number of the students are noted about 636 junior and 738 senior students. From this two sub population amounts which not homogeneous, selected 468 students as sample base on Slovin formula and by using probability sampling technique. As respondent, the students are met when they are present in campus and not receiving lesson, during research period. Only 427 units data which can be analyzed by using ANOVA. Result of research indicates that there is no difference level of fear to oral communication between junior students with senior student. Under assumption that junior students and senior student as homogeneous population, then this result can concluded that learning process can increase ability of oral communication of students. Keywords : Oral Communication, Learning Process
Quasi-perfect codes with small distance

The main purpose of this paper is to give bounds on the length of the shortest and longest binary quasi-perfect codes with a given Hamming distance, covering radius, and redundancy. We consider codes with Hamming distance 4 and 5 and covering radius 2 and 3, respectively. We discuss the blockwise direct sum (BDS) construction which has an important role in finding these bounds.
In Vitro and In Vivo Effects of Granulocyte Colony-Stimulating Factor on Neutrophils in Glycogen Storage Disease Type IB: Granulocyte Colony-Stimulating Factor Therapy Corrects the Neutropenia and the Defects in Respiratory Burst Activity and Ca2+ Mobilization

ABSTRACT: Children with glycogen storage disease (GSD) type 1b are susceptible to recurrent bacterial infections and have chronic neutropenia accompanied by phagocytic cell dysfunction including decreased superoxide anion (O2−) generation, calcium (Ca2+) mobilization, and chemotactic activity. Granulocyte colony-stimulating factor (G-CSF), a cytokine that corrects neutropenia in other diseases, in vitro enhances f-Met-Leu-Phe-triggered neutrophil O2− generation. Short-term pretreatment (15 min) of GSD 1b neutrophils with G-CSF increased the rate of O2− production (p < 0.01); however, this rate was still significantly below the rate of O2− production in control neutrophils. Recombinant human G-CSF (5 μg/kg/d) was administered s.c. to a GSD 1b patient. Before treatment, absolute neutrophil counts were < 500/mm3. Two d after G-CSF administration, the absolute neutrophil counts increased to 1333 and remained in the normal range during a 12-mo follow-up period. In vivo, G-CSF therapy increased f-Met-Leu-Phe-stimulated O2− production to 52% of control after 1 mo, and by mo 4, O2− production reached control levels. Our previous studies (J Clin Invest 56:196–202, 1990) demonstrated that decreased O2− production in neutrophils was associated with impaired Ca2+ mobilization. In vivo administration of G-CSF increased f-Met-Leu-Phe-triggered Ca2+ mobilization by neutrophils to 43% of control by mo 1 of G-CSF therapy and to 93% of control by mo 4, thus paralleling the improvements in O2− generation. In contrast, G-CSF therapy had no effect on the defective neutrophil chemotaxis. In summary, G-CSF therapy produced a rapid increase in circulating neutrophils and a gradual correction of O2− production. Long-term exposure to G-CSF may be required for correction of both neutropenia and O2− production in GSD 1b patients.
Increased mucosal synthesis of rheumatoid factor (RF) in coeliac disease

Increased serum levels of RF have been reported in patients with gluten sensitivity. The objective of this study was to investigate the in vivo secretion of different isotypes of RF in the small bowel in coeliac disease. Nineteen patients were investigated by perfusion of a defined jejunal segment, and the jejunal perfusion fluid was analysed for the presence of IgA and IgM anti‐Fc (IgG). Five of the patients studied had serum IgA deficiency. Patients with partial/subtotal villous atrophy but no IgA deficiency (n = 7) had a four‐fold increase of IgM‐RF (P<0.001) and a three‐fold increase of IgA‐RF (P<0.001) compared with healthy controls (n = 29). Patients with normal jejunal mucosa but no IgA deficiency (n = 7) had similar IgA‐RF and IgM‐RF concentrations to healthy controls. Patients with serum IgA deficiency had no IgA‐RF detectable in jejunal fluid but the highest IgM‐RF concentrations, in particular in active disease. The coeliac patients had serum levels of IgA‐RF and IgM‐RF within the reference ranges. Jejunal fluid levels of IgA‐RF and IgA‐anti‐gliadin antibodies were significantly correlated (P<0.001). The data indicate that enhanced jejunal mucosal production of RF occurs above all in active coeliac disease. The findings suggest that the immune response to gluten induces a mucosal RF synthesis.
Regulated recycling of mutant CFTR is partially restored by pharmacological treatment

Summary Efficient trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) to and from the cell surface is essential for maintaining channel density at the plasma membrane (PM) and ensuring proper physiological activity. The most common mutation, F508del, exhibits reduced surface expression and impaired function despite treatment with currently available pharmacological small molecules, called correctors. To gain more detailed insight into whether CFTR enters compartments that allow corrector stabilization in the cell periphery, we investigated the peripheral trafficking itineraries and kinetics of wild type (WT) and F508del in living cells using high-speed fluorescence microscopy together with fluorogen activating protein detection. We directly visualized internalization and accumulation of CFTR WT from the PM to a perinuclear compartment that colocalized with the endosomal recycling compartment (ERC) markers Rab11 and EHD1, reaching steady-state distribution by 25 minutes. Stimulation by protein kinase A (PKA) depleted this intracellular pool and redistributed CFTR channels to the cell surface, elicited by reduced endocytosis and active translocation to the PM. Corrector or temperature rescue of F508del also resulted in targeting to the ERC and exhibited subsequent PKA-stimulated trafficking to the PM. Corrector treatment (24 hours) led to persistent residence of F508del in the ERC, while thermally destabilized F508del was targeted to lysosomal compartments by 3 hours. Acute addition of individual correctors, C4 or C18, acted on peripheral trafficking steps to partially block lysosomal targeting of thermally destabilized F508del. Taken together, corrector treatment redirects F508del trafficking from a degradative pathway to a regulated recycling route, and proteins that mediate this process become potential targets for improving the efficacy of current and future correctors.