Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutrophil-Derived Elastase Induces TGF-β1 Secretion in Human Airway Smooth Muscle via NF-κB Pathway

Neutrophils are infiltrated in airways of individuals with more severe and chronic asthma, with uncertain significance. Airway smooth muscle (ASM), apart from its contractile properties, is critically involved in the pathogenesis of asthma by producing inflammatory mediators. In the present study, we investigated the impact of neutrophil-derived elastase (NE) on ASM in terms of TGF-beta1 release, and we explored the underlying mechanisms. Primary ASM cells were serum starved for 24 h before stimulation with NE (0.01-0.5 microg/ml). TGF-beta1 in supernatant was determined by ELISA and mRNA quantified by real-time RT-QPCR. NF-kappaB nuclear translocation and activation was examined by Western blotting and kappaB-2 dEGFP reporter gene assay. Association of IL-1 receptor-associated kinase (IRAK) with MyD88 was studied by co-immunoprecipitation and Toll-like receptor 4 (TLR4) determined by FACS scan and Western blotting. We demonstrated that NE enhanced TGF-beta1 release in a time-dependent manner. This induction was inhibited by actinomycin D (5 mM), cycloheximide (5 mM), and NF-kappaB inhibitors, including pyrrolidine dithiocarbamate (PDTC, 1 mM), aspirin (2.5 mM), and sodium salyicylate (2.5 mM). Stimulation with NE was rapidly followed by association of IRAK with MyD88, phosphorylation of IkappaBalpha, and nuclear translocation of p65 with increased transactivation activity. We also found that TLR4 levels were reduced upon NE treatment. These data suggest that NE upregulates TGF-beta1 gene expression and release via My88/IRAK/NF-kappaB pathway, possibly through activation of TLR4, and shed light on a potential role of neutrophils in the pathogenesis of asthma.
Clinical advances in therapies targeting the interleukin-2 receptor.

A dominant theme in modern immunological research is the elucidation of how the different branches of the immune system communicate. Identification of receptors for antigens, co‐receptors such as CD4 and CD8, major histocompatibility complex (MHC) molecules and cytokine receptors, has gone a long way to giving a clearer view of the complexities of this interaction. More recently, this new information has opened up avenues for therapeutic intervention by directing novel treatments towards these various receptors. This new strategy of immune‐receptor‐directed therapy has been applied to an array of human disorders both in the laboratory and clinical settings. Perhaps one of the most important, and certainly most studied, cytokines is interleukin‐2 (IL‐2). This molecule was first identified in 1976 by Morgan as a substance present in the supernatant of activated peripheral blood lymphocytes that was capable of driving the growth and proliferation of lymphocytes in vivo . 1 Recent molecular biological advances have allowed development of recombinant IL‐2 and inhibitors of its cellular receptor. This review focuses on the basic biology of IL‐2 and its receptor, and examines the clinical applications of IL‐2 receptor‐targeted therapies. Recombinant IL‐2 has also been extensively used in treatment of various malignancies, but for reasons of space, I will not further examine this issue. I searched through the databases Medline, Embase and Pre‐Medline using the key words interleukin‐2 and interleukin‐2 receptor. I used recent reviews from these searches along with original articles on the subject. IL‐2 is a single polypeptide of molecular weight 15.5 kDa, 133 amino acid residues long. There is only a single IL‐2 gene locus in humans, on chromosome 4. IL‐2 is a globular protein containing two sets of α‐helical domains, lying at right angles to each other.2 These α‐helical regions are involved in the binding to the receptor, and indeed this helical …
Head-to-Head Comparisons of Hydrochlorothiazide With Indapamide and Chlorthalidone: Antihypertensive and Metabolic Effects

Hydrochlorothiazide (HCTZ) has often been contrasted with chlorthalidone, but relatively little is known about HCTZ versus indapamide (INDAP). This systematic review retrieved 9765 publications, and from these, it identified 14 randomized trials with 883 patients comparing HCTZ with INDAP and chlorthalidone on antihypertensive potency or metabolic effects. To make fair comparisons, the dose of the diuretic in each arm was assigned 1 of 3 dose levels. In random effects meta-analysis, INDAP and chlorthalidone lowered systolic blood pressure more than HCTZ: −5.1 mm Hg (95% confidence interval, −8.7 to −1.6); P=0.004 and −3.6 mm Hg (95% confidence interval, −7.3 to 0.0); P=0.052, respectively. For both comparisons, there was minimal heterogeneity in effect across trials and no evidence for publication bias. The HCTZ–INDAP contrast was biased in favor of greater HCTZ potency because of a much greater contribution to the overall effect from trials in which the HCTZ arm had a higher dose level than the INDAP arm. For the HCTZ–INDAP comparison, no single trial was responsible for the overall result nor was it possible to detect significant modifications of this comparison by duration of follow-up, high- versus low-bias trials, or the presence or absence of background medications. There were no detectable differences between HCTZ and INDAP in metabolic adverse effects, including effects on serum potassium. In conclusion, these head-to-head comparisons demonstrate that, like chlorthalidone, INDAP is more potent than HCTZ at commonly prescribed doses without evidence for greater adverse metabolic effects.
Old inflation in string theory

We propose a stringy version of the old inflation scenario which does not require any slow-roll inflaton potential and is based on a specific example of string compactification with warped metric. Our set-up admits the presence of anti-D3-branes in the deep infrared region of the metric and a false vacuum state with positive vacuum energy density. The latter is responsible for the accelerated period of inflation. The false vacuum exists only if the number of anti-D3-branes is smaller than a critical number and the graceful exit from inflation is attained if a number of anti-D3-branes travels from the ultraviolet towards the infrared region. The cosmological curvature perturbation is generated through the curvaton mechanism.
Absence of Asymptomatic Malaria Infection in Endemic Area of Bashagard District, Hormozgan Province, Iran

Background A successful malaria elimination program calls for enough attention to parasite carriers, especially asymptomatic malaria, as well as the diagnosis and treatment of clinical cases. Asymptomatic malaria is an infection that patients do not show any symptom; thus, these patients play critical role in the concept of an elimination program. The current investigation was conducted to evaluate the presence of these cases in Bashagard District, formerly a high malaria transmission area in Hormozgan Province, Iran. Methods Blood samples (n = 500) were collected from symptomless individuals residing in Bashagard to evaluate Plasmodium infection by using microscopic, serological and nested-PCR techniques. Results Regarding the microscopic and nested-PCR analysis, no asymptomatic infection was detected among studied individuals. Totally, 1% of the studied population (5 of 500) had anti PvMSP-119-specific IgG antibody; however, only 0.2% (1 of 500) of the individuals was seropositive to recombinant PfMSP-119, using ELISA. Conclusion This study showed no asymptomatic malaria infection in the studied population; hence malaria elimination is feasible and can be successfully carried out in this region.
Authenticated and persistent skip graph: a data structure for cloud based data-centric applications

Cloud computing has evolved as a popular computing environment. In data centric applications hosted on the cloud, data is accessed and updated in a purely distributed manner. The distributed data structures used for dynamic storage of the data for such applications require two fundamental qualities, authentication and persistence, which are not completely met by existing distributed data structures. Authentication is a crucial requirement for data structures used on the cloud, as users need to be convinced about the validity of the data they receive. Moreover the data structure has to be persistent, so that changes can be made to the data structure without losing old data, or old versions of the data structure, which may be required by different users in the distributed environment. In this paper we present authenticated and persistent skip graph, an enhanced variant of the existing skip graph. It is based on an event based model, to correspond to the distributed data centric application requirements. Skip graphs are randomized data structures based on skip lists, proposed for use in distributed applications. But skip graphs are neither persistent nor authenticated. The fat node technique is adapted here for providing persistence, and a role based access control, with a cryptographic scheme is used to ensure valid data update and verify the validity of the retrieved data. Our data structure is proved to be efficient in terms of time and space complexities.
Optimal power allocation and relay location for decode-and-forward dual-hop systems over Weibull fading channels

This paper addresses the power allocation (PA) and relay location problems in a dual-hop decode-and-forward relaying system over Weibull fading channels. The optimization problems such as optimal relay location with fixed power allocation, adaptive PA with fixed relay location and joint optimization of the PA and relay location, are investigated in order to maximize the ergodic capacity under identical Weibull fading. The above problems are also discussed to minimize the outage probability over non-identical Weibull fading channels. Numerical results show that the adaptive algorithms outperform fixed allocation schemes.
Metal-Based Nanoparticles and the Immune System: Activation, Inflammation, and Potential Applications

Nanomaterials, including metal-based nanoparticles, are used for various biological and medical applications. However, metals affect immune functions in many animal species including humans. Different physical and chemical properties induce different cellular responses, such as cellular uptake and intracellular biodistribution, leading to the different immune responses. The goals of this review are to summarize and discuss the innate and adaptive immune responses triggered by metal-based nanoparticles in a variety of immune system models.
LSU Digital Commons LSU Digital Commons A characterization of box-mengerian matroid ports A characterization of box-mengerian matroid ports

Let M be a matroid on E ∪ { (cid:96) } , where (cid:96) (cid:54)∈ E is a distinguished element of M . The (cid:96) -port of M is the set P = { P : P ⊆ E with P ∪ { (cid:96) } a circuit of M } . Let A be the P - E incidence matrix. Let U 2 , 4 be the uniform matroid on four elements of rank two, F 7 be the Fano matroid, F ∗ 7 be the dual of F 7 , and F +7 be the unique series extension of F 7 . In this paper, we prove that the system A x ≥ 1 , x ≥ 0 is box-totally dual integral (box-TDI) if and only if M has no U 2 , 4 -minor using (cid:96) , no F ∗ 7 -minor using (cid:96) , and no F +7 -minor using (cid:96) as a series element. Our characterization yields a number of interesting results in combinatorial optimization.
Investigation of Torque–Speed Characteristics and Cogging Torque of Fractional-Slot IPM Brushless AC Machines Having Alternate Slot Openings

This paper presents a comparative study of torque-speed characteristics and cogging torque of the fractional-slot interior permanent magnet brushless ac machines having different slot openings, viz. open slot, closed slot, and hybrid slot (sandwiched open and closed slots), and unskewed and step skewed rotors. The influence of such alternate slot openings on the magnetic cross-coupling and cogging torque is particularly emphasized. Furthermore, the repercussion of the manufacturing limitations and tolerances on the cogging torque of machines having these alternate slot openings is also investigated. The magnetic cross-coupling level and the sensitivity of cogging torque to manufacturing limitations and tolerances strongly depend on the slot opening materials. The finite-element analyses are experimentally validated.
Effects of Demographic Factors on Survival Time after a Diagnosis of Amyotrophic Lateral Sclerosis

Background: The Agency for Toxic Substances and Disease Registry established surveillance projects to determine the incidence, prevalence, and demographic characteristics of persons with Amyotrophic Lateral Sclerosis (ALS) in defined geographic areas. There is a need to characterize and account for the survival and prognostic factors among a population-based cohort of ALS cases in the United States. Methods: A cohort of incident cases diagnosed from 2009-2011 in New Jersey was followed until death or December 31, 2013, whichever happened first. Survival was assessed using Kaplan-Meier curves and Cox proportional hazards regression was used to identify prognostic factors. Results: Sixty-four percent of incident cases died between 2009 and 2013, 93.7% specifically from ALS. Among the 456 cases studied in the survival analysis, the median survival from diagnosis was 21 months; 46% of cases survived longer than two years from diagnosis. Older age predicted shorter survival. While there is some indication of differences because of sex, race, and ethnicity, these differences were not statistically significant when accounting for age. Conclusions: New Jersey mortality data were queried to determine the vital status of a cohort of incident ALS cases and used to investigate relationships between demographic factors and survival. Results are consistent with other population-based studies. Older age was a strong predictor of shorter survival time. Additional follow-up time is needed to characterize longer-term survival.
Protein tyrosine phosphatases ε and α perform nonredundant roles in osteoclasts

The closely related tyrosine phosphatases PTPa and PTPe fulfill distinct roles in osteoclasts. The various effects of each PTP on podosome organization in osteoclasts are caused by their distinct N-termini. The function of PTPe in these cells requires the presence of its 12 N-terminal residues, in particular serine 2.
Real-Time Diffusion of Information on Twitter and the Financial Markets

Do spikes in Twitter chatter about a firm precede unusual stock market trading activity for that firm? If so, Twitter activity may provide useful information about impending financial market activity in real-time. We study the real-time relationship between chatter on Twitter and the stock trading volume of 96 firms listed on the Nasdaq 100, during 193 days of trading in the period from May 21, 2012 to September 18, 2013. We identify observations featuring firm-specific spikes in Twitter activity, and randomly assign each observation to a ten-minute increment matching on the firm and a number of repeating time indicators. We examine the extent that unusual levels of chatter on Twitter about a firm portend an oncoming surge of trading of its stock within the hour, over and above what would normally be expected for the stock for that time of day and day of week. We also compare the findings from our explanatory model to the predictive power of Tweets. Although we find a compelling and potentially informative real-time relationship between Twitter activity and trading volume, our forecasting exercise highlights how difficult it can be to make use of this information for monetary gain.
Brain regions involved in the recognition of happiness and sadness in music

Here, we used functional magnetic resonance imaging to test for the lateralization of the brain regions specifically involved in the recognition of negatively and positively valenced musical emotions. The manipulation of two major musical features (mode and tempo), resulting in the variation of emotional perception along the happiness–sadness axis, was shown to principally involve subcortical and neocortical brain structures, which are known to intervene in emotion processing in other modalities. In particular, the minor mode (sad excerpts) involved the left orbito and mid-dorsolateral frontal cortex, which does not confirm the valence lateralization model. We also show that the recognition of emotions elicited by variations of the two perceptual determinants rely on both common (BA 9) and distinct neural mechanisms.
Insulin is an independent correlate of plasma homocysteine levels in obese children and adolescents.

OBJECTIVE The aim of the study was to investigate whether anthropometric and metabolic risk factors for coronary heart disease (CHD) contribute to the variation in homocysteine levels in obese children and adolescents. RESEARCH DESIGN AND METHODS A total of 84 children and adolescents were assessed for fasting total homocysteine, methylenetetrahydrofolate reductase polymorphism (C677T mutation), folate and vitamin B12 status, and anthropometric and metabolic risk factors for CHD. RESULTS No significant sex differences were found for all available anthropometric and metabolic characteristics except for homocysteine, which was significantly higher in boys than in girls (7.1 vs. 6.3 micromol/l; P<0.05). After adjustment for age and sex, homocysteine correlated significantly with BMI, fat mass, percentage of fat mass, and insulin and showed an inverse correlation with folate levels. Homocysteine did not correlate with vitamin B12; total cholesterol; LDL, HDL, and VLDL; triglycerides; and glucose. BMI and fat mass correlated significantly with insulin and showed a significant inverse correlation with folate. We found no association between homocysteine and the C677T mutation. In multiple regression analyses, insulin was found to be the main correlate of homocysteine. CONCLUSIONS Our study demonstrates for the first time that insulin is a main correlate of homocysteine in obese children and adolescents and suggests that fat mass-associated hyper-insulinism may contribute to impairment of homocysteine metabolism in childhood obesity
Development of Fibrosis in Nonalcoholic Steatosis through Combination of a Synthetic Diet Rich in Disaccharide and Low-Dose Lipopolysaccharides in the Livers of Zucker (fa/fa) Rats

Nonalcoholic steatohepatitis (NASH) can develop into end-stage disease such as cryptogenic cirrhosis and hepatocellular carcinoma. Hence, it is important to understand the pathogenesis of NASH. In general, the “two-hit theory” has prevailed as a pathogenic mechanism of NASH. According to this theory, lipopolysaccharides (LPS) contained in normal portal blood are the “second hit,” but their role is not completely understood. Based on this theory, we evaluated the role of LPS in NASH pathogenesis. For the first hit to develop metabolic abnormalities, a synthetic diet rich in disaccharide (synthetic diet: 12.1 cal% disaccharide) was fed to Zucker (fa/fa) rats for 12 weeks. For the second hit, 100 µg/kg LPS was injected intraperitoneally once daily for 2 weeks. Synthetic diet-fed rats treated with LPS showed an increase in the triglyceride content and higher expression of profibrogenic mRNAs in the liver. Plasma alanine aminotransferase levels were significantly elevated using this protocol. Furthermore, histological examination demonstrated that this protocol induced mild hepatic fibrosis and focal necrosis in the livers of all rats. Synthetic diet-fed Zucker (fa/fa) rats treated with LPS could be useful for understanding the development of hepatic fibrosis in the two-hit theory.
Stimulation by cadmium of myohemerythrin-like cells in the gut of the annelid Nereis diversicolor

SUMMARY Isolated guts of Nereis diversicolor revealed the existence of a cadmium-binding protein, the MPII, belonging to the group of hemerythrins and myohemerythrins. The presence of MPII in the cells of the intestine was demonstrated by immunocytochemistry, using anti-MPII, a monoclonal antibody. In addition, using in situ hybridization and northern blotting, it was shown that MPII-cells are the site of synthesis of this molecule. Exposure of the worms to cadmium led to the cellular activation process of MPII-cells (i.e. transformation of the nucleolus, development of the endoplasmic reticulum and the Golgi apparatus), although MPII mRNA transcript levels were unchanged. Enzyme-linked immunosorbent assay (ELISA) of gut extracts revealed that MPII levels were increased after exposure to Cd, so it appears that this protein is synthesized as a response to Cd exposure without any new synthesis of mRNA. This mechanism of regulation is quite similar to that reported in the case of mammalian ferritin and may be involved in the regulation of Cd levels in this worm.
Flying with the birds? Recent large-area dispersal of four Australian Limnadopsis species (Crustacea: Branchiopoda: Spinicaudata)

Temporary water bodies are important freshwater habitats in the arid zone of Australia. They harbor a distinct fauna and provide important feeding and breeding grounds for water birds. This paper assesses, on the basis of haplotype networks, analyses of molecular variation and relaxed molecular clock divergence time estimates, the phylogeographic history, and population structure of four common temporary water species of the Australian endemic clam shrimp taxon Limnadopsis in eastern and central Australia (an area of >1,350,000 km2). Mitochondrial cytochrome c oxidase subunit I sequences of 413 individuals and a subset of 63 nuclear internal transcribed spacer 2 sequences were analyzed. Genetic differentiation was observed between populations inhabiting southeastern and central Australia and those inhabiting the northern Lake Eyre Basin and Western Australia. However, over large parts of the study area and across river drainage systems in southeastern and central Australia (the Murray–Darling Basin, Bulloo River, and southern Lake Eyre Basin), no evidence of population subdivision was observed in any of the four Limnadopsis species. This indicates recent gene flow across an area of ∼800,000 km2. This finding contrasts with patterns observed in other Australian arid zone taxa, particularly freshwater species, whose populations are often structured according to drainage systems. The lack of genetic differentiation within the area in question may be linked to the huge number of highly nomadic water birds that potentially disperse the resting eggs of Limnadopsis among temporary water bodies. Genetically undifferentiated populations on a large geographic scale contrast starkly with findings for many other large branchiopods in other parts of the world, where pronounced genetic structure is often observed even in populations inhabiting pools separated by a few kilometers. Due to its divergent genetic lineages (up to 5.6% uncorrected p-distance) and the relaxed molecular clock divergence time estimates obtained, Limnadopsis parvispinus is assumed to have inhabited the Murray–Darling Basin continuously since the mid-Pliocene (∼4 million years ago). This means that suitable temporary water bodies would have existed in this area throughout the wet–dry cycles of the Pleistocene.