Miracle-dz/UniFAR-FTUs huggingface dataset:
Greater pathogen burden but not elevated C-reactive protein increases the risk of clinical restenosis after percutaneous coronary intervention.

BACKGROUND Restenosis after percutaneous coronary intervention (PCI) constitutes a serious complication in the treatment of cardiovascular disease, but known risk factors do not fully account for the observed restenosis risk. Preliminary studies of infection or inflammation in restenosis report varied results. We tested whether C-reactive protein (CRP) or pathogen burden (seropositivity to 0, 1, 2, or 3 pathogens, of Chlamydia pneumoniae [Cpn], cytomegalovirus [CMV], or Helicobacter pylori [Hpy]) predict clinical restenosis after percutaneous coronary intervention (PCI). METHODS Blood samples were collected from 415 patients undergoing PCI, and levels of plasma CRP and antibodies to Cpn, CMV, and Hpy were measured. The patient's medical history, demographics, and procedural data were recorded. Patient end points were determined for as long as 6 months as a means of evaluating the incidence of clinical restenosis and major adverse cardiac events. RESULTS The average patient age was 62 years, and 80% of patients were male. Fifty-eight patients (14%) experienced clinical restenosis, whereas 17 patients (4%) died or had an acute myocardial infarction. After adjusting for 19 possible predictors, we found the pathogen burden (P-trend =.04, adjusted odds ratio [OR] 1.5 per number of pathogens) and minimum luminal diameter (P =.003, OR 1.8 per mm decrease) to be significant predictors of clinical restenosis. Male sex was a nonsignificant predictor of restenosis (P =.06, OR 2.2), but CRP was not significant after adjustment (P-trend =.10, OR 0.73 per tertile). CONCLUSION Pathogen burden was associated with clinical coronary restenosis, an association that deserves further exploration and evaluation. CRP, a marker of inflammation, was not associated with an increased risk of restenosis.
Human adipocyte function is impacted by mechanical cues

Fibrosis is a hallmark of human white adipose tissue (WAT) during obesity‐induced chronic inflammation. The functional impact of increased interstitial fibrosis (peri‐adipocyte fibrosis) on adjacent adipocytes remains unknown. Here we developed a novel in vitro 3D culture system in which human adipocytes and decellularized material of adipose tissue (dMAT) from obese subjects are embedded in a peptide hydrogel. When cultured with dMAT, adipocytes showed decreased lipolysis and adipokine secretion and increased expression/production of cytokines (IL‐6, G‐CSF) and fibrotic mediators (LOXL2 and the matricellular proteins THSB2 and CTGF). Moreover, some alterations including lipolytic activity and fibro‐inflammation also occurred when the adipocyte/hydrogel culture was mechanically compressed. Notably, CTGF expression levels correlated with the amount of peri‐adipocyte fibrosis in WAT from obese individuals. Moreover, dMAT‐dependent CTGF promoter activity, which depends on β1‐integrin/cytoskeleton pathways, was enhanced in the presence of YAP, a mechanosensitive co‐activator of TEAD transcription factors. Mutation of TEAD binding sites abolished the dMAT‐induced promoter activity. In conclusion, fibrosis may negatively affect human adipocyte function via mechanosensitive molecules, in part stimulated by cell deformation. Published by John Wiley & Sons, Ltd
Isolation and characterization of salivary antigens from Hyalomma anatolicum anatolicum

Summary This study demonstrates the involvement of a large number of salivary proteins in the acquisition of resistance to Hyalomma anatolicum anatolicum. Using immunoblotting, sera from hypersensitized rabbits were shown to react with nine proteins in the saliva and 17 in salivary gland extracts (SGE) from 96 h fed female ticks. The salivary antigens had molecular weights in the range of 14 400 to 130000. All the antigens identified in the saliva and 12 of the SGE antigens were glycoprotein in nature and a majority of them appeared to be common to different stages of feeding. In addition antigen I (molecular weight 130000) showed acid phosphatase and antigen III (molecular weight 96000) showed both non‐specific esterase and aminopeptidase activity. Three high molecular weight proteins isolated from saliva (antigen I, antigen II–molecular weight 103 000 and antigen III), gave immediate hypersensitivity reactions in intradermal inoculation into rabbits which had previously been exposed to ticks. Antigens II and III also elicited a strong delayed hypersensitivity reaction. These results may help to explain the nature of the immune mechanisms which effect resistance against H. a. anatolicum.
Airway Hyperresponsiveness: From Molecules to Bedside Selected Contribution: How does airway inflammation modulate asthmatic airway constriction? An antigen challenge study

During the late-phase (LP) response to inhaled allergen, mediators from neutrophils and eosinophils are released within the airways, resembling what occurs during an asthma attack. We compared the distribution of obstruction and degree of reversibility that follows a deep inspiration (DI) during early-phase (EP) and LP responses in nine asthmatic subjects challenged with allergen. Heterogeneity of constriction was assayed by determining frequency dependence of dynamic lung resistance and elastance, airway caliber by tracking airway resistance during a DI, and airway inflammation by measuring inflammatory cells in induced sputum postchallenge. Despite a paucity of eosinophils in the sputum at baseline (<1% of nonsquamous cells), asthmatic subjects showed a substantial EP response with highly heterogeneous constriction and reduced capacity to maximally dilate airways. The LP was associated with substantial airway inflammation in all subjects. However, five subjects showed only mild LP constriction, whereas .
GST Reform in Australia: Implications of Estimating Price Elasticities of Demand for Food

This paper uses detailed information about household supermarket purchases from the Australian Nielsen Homescan Survey to estimate price elasticities of demand for a range of food categories. An instrumental variable strategy is employed to address endogeneity issues. The estimates obtained from our analysis are used to study five scenarios in which the rate of the GST on food categories is increased or in which the tax base is broadened to include currently GST-free categories. Our findings reveal that there is considerable scope for raising revenue by increasing the rate and broadening the tax base. Low-income households (the bottom 40% of the income distribution) can be compensated for the loss in consumption induced by a tax increase. We demonstrate that increasing the rate of the GST from 10% to 15% and broadening the tax base would increase tax revenues by up to $8.6 billion, whereas compensating lowincome households would require up to $2.2 billion. We also provide a detailed list of tax revenues and compensation payments associated with each food category to allow readers to “build their own tax reform” by choosing the categories that should be taxed.
A formal approach to slack-driven high-level synthesis

With the advent of deep sub micron era, design closure is becoming harder to achieve. In high-level synthesis, slack is a very effective means of tolerating uncertainties. Thus, several research efforts have been paid to study the slack-driven high-level synthesis problem. However, previous works cannot actually maximize the total slack value, because they are limited to either the operation scheduling stage or the resource binding stage. In this paper, we study the simultaneous operation scheduling and resource binding for the maximization of the total slack value. An integer linear programming approach is proposed for formally draw up the slack-driven high-level synthesis problem. Note that our approach guarantees maximizing the total slack value. Compared with the combination of previous works (i.e., slack-driven operation scheduling followed by slack-driven resource binding), experimental data show that our approach can greatly reduce the total slack value without any design overhead.
Separate DNA Elements Containing ATF/CREB and IE86 Binding Sites Differentially Regulate the Human Cytomegalovirus UL112-113 Promoter at Early and Late Times in the Infection

ABSTRACT The human cytomegalovirus (HCMV) UL112-113 promoter represents a useful model for studying temporal regulation of viral gene expression. Stimulation of this promoter by the 86-kDa immediate-early protein (IE86) is controlled by sequences between nucleotides −113 and −59, which include both an ATF/CREB and an IE86 binding site. In transient assays, the ATF/CREB site is essential, and the IE86 site, although nonessential, can enhance transcription. With recombinant viruses, we have assessed the function of these promoter elements in the context of the viral genome. Transcription from the inserted UL112-113 promoter shows the same temporal pattern as the endogenous promoter, including the switch to an upstream RNA start site late in infection. Deletion of sequences containing the IE86 site results in a decrease in the level of early transcription and elimination of late transcription. In contrast, when the ATF/CREB site is deleted, early RNA synthesis is almost completely abolished, but late transcription is comparable to that of the wild type, with repositioning of the RNA start site downstream by the number of nucleotides deleted. Replacement of sequences between −108 and −95 with the HCMVcis-repression signal from the major immediate-early promoter had no effect on the level of late RNAs but resulted in the repositioning of the RNA start site 39 nucleotides upstream. These results suggest that the ATF/CREB site is functional only at early times, while sequences containing the IE86 site modulate the level of early RNAs and may be required for activating late transcription in a distance-dependent manner.
iPGK-PseAAC: Identify Lysine Phosphoglycerylation Sites in Proteins by Incorporating Four Different Tiers of Amino Acid Pairwise Coupling Information into the General PseAAC.

BACKGROUND Occurring at Lys residues, the PGK (lysine phosphoglycerylation) is a special kind of post-translational modification (PTM). It may invert the charge potential of the modified residue and change the protein structures and functions, causing various diseases in liver, brain, and kidney. OBJECTIVE From the angles of both basic research and drug development, we are facing a critical challenging problem: for an uncharacterized protein sequence containing many Lys residues, which ones can be of phosphoglycerylation, and which ones cannot? METHOD To address this problem, we have developed a predictor called iPGK-PseAAC by incorporating into the general PseAAC (pseudo amino acid composition) with four different tiers of amino acid pairwise coupling information, where tiers 1, 2, 3, and 4 refer to the amino acid pairwise couplings between all the 1st, 2nd, 3rd, and 4th most contiguous residues along a protein segment, respectively. RESULTS Rigorous cross-validations indicated that the proposed predictor remarkably outperformed its existing counterparts. CONCLUSION The proposed predictor iPGK-PseAAC will become a very useful bioinformatics tool for medicinal chemistry. For the convenience of most experimental scientists, a user-friendly webserver for iGPK-PseAAC has been established at http://app.aporc. org/iPGK-PseAAC/, by which users can easily obtain their desired results without the need to go through the complicated mathematical equations involved.
The Determinants of Firm Survival in South Africa

In developing economies the existence of a healthy corporate structure is vital to the pursuit of long term policy objectives of employment and sustainable economic growth. This makes it important to understand what determines firm survival and while there is a growing literature on the topic, there is limited coverage of developing economies because of data limitations. This paper uses a unique dataset on a panel of companies listed in the Johannesburg Stock Exchange (JSE) in South Africa during the period 2000-2010 obtained from the DataStream service to analyse the patterns of survival and investigate the determinants of firm survival. It starts by considering the patterns of growth and survival over the 2000-10 period and specifies some simple logit binary survival models that allow for firm size, age and financial characteristics. These models are improved upon using the non-parametric Kaplan-Meier product limit method and estimating Cox proportional hazard model. Fifty per cent of the companies listed in the JSE survived for the whole period and the determinants of their survival would seem to be consistent with expectations with highly leveraged, highly profitable large firms in primary sector having the highest chance of survival. Surprisingly, Age and the origin of the firm do not seem to be significant factors in determining survival.
A Recombinant Vaccinia Virus Encoding the Interferon‐Inducible T‐Cell Alpha Chemoattractant is Attenuated In Vivo

Murine interferon‐inducible T‐cell alpha chemoattractant (I‐TAC) is a potent non‐ELR CXC chemokine that predominantly attracts activated T lymphocytes, binds to the receptor CXCR3 and is induced by interferon‐γ (IFN‐γ). We analysed I‐TAC expression by reverse transcriptase‐polymerase chain reaction during three different virus‐infection models in mice, respiratory syncytial virus (RSV), influenza A and vaccinia virus western reserve (VV‐WR). In the lungs from mice infected with RSV or influenza A viruses, peak expression of I‐TAC coincided with peak viraemia. Surprisingly, there was no expression in the lungs of mice infected with vaccinia, unlike the elevated expression shown previously for other interferon‐regulated chemokines, such as Crg2 and Mig. To further investigate the importance of this difference during vaccinia infection in mice, a recombinant virus encoding I‐TAC (rVV I‐TAC) was generated. Studies in C57BL/6 and Swiss nude mice showed that I‐TAC expression caused increased mononuclear cell infiltration and significantly attenuated the VV. Infection of the footpads of naïve or already immune (with VV‐WR) mice with either rVV I‐TAC or VV‐WR demonstrated that I‐TAC expression reduced overall inflammation during infection and that this reduction was more pronounced in already immune mice. The data presented here show that I‐TAC can have an important role during virus infections and that vaccinia has evolved ways to avoid inducing I‐TAC expression.
Cold Ischemia Time and Allograft Outcomes in Live Donor Renal Transplantation: Is Live Donor Organ Transport Feasible?

One of the greatest obstacles to the implementation of regional or national kidney paired donation programs (KPD) is the need for the donor to travel to their matched recipient's hospital. While transport of the kidney is an attractive alternative, there is concern that prolonged cold ischemia time (CIT) would diminish the benefits of live donor transplantation (LDTx). To examine the impact of increased CIT in LDTx, 1‐year serum creatinine (SCr), delayed graft function (DGF), acute rejection (AR) and allograft survival (AS) were analyzed in 38 467 patients by 2 h CIT groups (0–2, 2–4, 4–6 and 6–8 h) using data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN). Adjusted probabilities of DGF and AR were estimated in multivariate logistic regression models and AS was examined in multivariate Cox proportional hazards models. Although some increase in DGF was observed between the 0–2 h (4.7%) and 4–6 h (8.3%) groups, prolonged CIT did not result in inferior SCr, increased AR or compromised AS in any group with >2 h CIT compared with the 0–2 h group. Comparable long‐term outcomes for these grafts suggests that transport of live donor organs may be a feasible alternative to donor travel in KPD regions where CIT can be limited to 8 h.
The microanatomy of human islets of Langerhans, with special reference to somatostatin (D-) cells.

The arrangement of the various endocrine cells within mammalian islets of Langerhans indicates that the regulation of insulin and glucagon secretion by pancreatic somatostatin may occur mainly by paracrine mechanisms. In the present study, the relationship of somatostatin-containing D-cells to blood vessels and to other endocrine cells in the islets of the human pancreas were investigated using immunohistochemically stained serial semithin sections (0.5-1.0 micron). Morphologic features of 335 D-cells were examined and their anatomical relationship to other endocrine cell types and capillaries was determined by morphometric analysis and graphic or three-dimensional reconstructions. The majority of D-cells (84%) was located in close proximity to the capillaries. The intracellular immunoreactive material was accumulated in those cell parts facing the capillaries or their perivascular spaces. The remaining D-cells did not come into contact with the capillaries and showed only moderate or weak immunoreactivity. --A further characteristic feature of islet D-cells, pertinent to about 67% of these cells, is their tendency to be arranged in contiguity to other D-cells. The present findings indicate that somatostatin after its release from the D-cell reaches other islet cells mainly via the intrainsular circulation or along the perivascular space. Concerning the general microarchitecture of human islets of Langerhans, the present data are not sufficient to give a conclusive morphological description, because heterogeneities among the islets were observed. These variations appear to be related to the type of vascular supply which differs among islets.
Sex differences and similarities in job attribute preferences: a meta-analysis.

Many researchers have studied sex differences in job attribute preferences. The authors meta-analyzed 242 samples collected from 321,672 men and boys and 316,842 women and girls in the United States between 1970 and 1998. Findings indicated significant (p < .05) sex differences on 33 of 40 job attribute preferences examined. The effect sizes were small. Of the 33 significant differences, 26 had average effect sizes of magnitude . 20 or less. The directions of the differences were generally consistent with gender roles and stereotypes. Many job attributes became relatively more important to women and girls in the 1980s and 1990s compared with the 1970s, indicating that women's aspirations to obtain job attributes rose as gender barriers to opportunity declined.
Incorporation of High Levels of Chimeric Human Immunodeficiency Virus Envelope Glycoproteins into Virus-Like Particles

ABSTRACT The human immunodeficiency virus (HIV) envelope (Env) protein is incorporated into HIV virions or virus-like particles (VLPs) at very low levels compared to the glycoproteins of most other enveloped viruses. To test factors that influence HIV Env particle incorporation, we generated a series of chimeric gene constructs in which the coding sequences for the signal peptide (SP), transmembrane (TM), and cytoplasmic tail (CT) domains of HIV-1 Env were replaced with those of other viral or cellular proteins individually or in combination. All constructs tested were derived from HIV type 1 (HIV-1) Con-S ΔCFI gp145, which itself was found to be incorporated into VLPs much more efficiently than full-length Con-S Env. Substitution of the SP from the honeybee protein mellitin resulted in threefold-higher chimeric HIV-1 Env expression levels on insect cell surfaces and an increase of Env incorporation into VLPs. Substitution of the HIV TM-CT with sequences derived from the mouse mammary tumor virus (MMTV) envelope glycoprotein, influenza virus hemagglutinin, or baculovirus (BV) gp64, but not from Lassa fever virus glycoprotein, was found to enhance Env incorporation into VLPs. The highest level of Env incorporation into VLPs was observed in chimeric constructs containing the MMTV and BV gp64 TM-CT domains in which the Gag/Env molar ratios were estimated to be 4:1 and 5:1, respectively, compared to a 56:1 ratio for full-length Con-S gp160. Electron microscopy revealed that VLPs with chimeric HIV Env were similar to HIV-1 virions in morphology and size and contained a prominent layer of Env spikes on their surfaces. HIV Env specific monoclonal antibody binding results showed that chimeric Env-containing VLPs retained conserved epitopes and underwent conformational changes upon CD4 binding.
Cataract-causing alphaAG98R mutant shows substrate-dependent chaperone activity.

PURPOSE The G98R mutation in human alphaA-crystallin is associated with autosomal dominant cataract (presenile type). The reasons for cataract development in alphaAG98R individuals are not fully understood. Therefore we undertook this study to analyze the stability, structural changes and chaperone function of alphaAG98R protein. METHODS Site-directed mutagenesis was employed to generate alphaAG98R mutant protein. Human alphaA-crystallin cDNA cloned into the pET23d vector was used as the template. The recombinant proteins were expressed in E. coli and purified using chromatographic methods. Both the wild-type and mutant proteins were characterized by SDS-PAGE, transmission electron microscopy, static and dynamic light scattering, and spectroscopic analysis. The chaperone-like function of the mutant protein was compared with wild-type protein using different substrates. RESULTS The G98R mutant protein formed larger oligomers compared to the wild-type alphaA-crystallin. Circular dichroism studies showed altered secondary and tertiary structure whereas bis-ANS binding studies showed a gain of surface hydrophobicity in the alphaAG98R protein. The alphaAG98R protein displayed a substrate-dependent chaperone-like activity. The mutant protein appeared to have diminished chaperone-like activity toward aggregating alpha-lactalbumin, whereas citrate synthase and alcohol dehydrogenase were efficiently protected from aggregation. CONCLUSIONS The present results reveal that the G98R mutation causes conformational changes in alphaA-crystallin and that with certain substrates the mutant protein forms complexes that are prone to precipitate over time. The accumulation of mutant protein-substrate complexes may be the reason for cataract development in individuals carrying the G98R mutation in alphaA-crystallin.
Synergistic Interactions between Aβ, Tau, and α-Synuclein: Acceleration of Neuropathology and Cognitive Decline

Alzheimer's disease (AD), the most prevalent age-related neurodegenerative disorder, is characterized pathologically by the accumulation of β-amyloid (Aβ) plaques and tau-laden neurofibrillary tangles. Interestingly, up to 50% of AD cases exhibit a third prevalent neuropathology: the aggregation of α-synuclein into Lewy bodies. Importantly, the presence of Lewy body pathology in AD is associated with a more aggressive disease course and accelerated cognitive dysfunction. Thus, Aβ, tau, and α-synuclein may interact synergistically to promote the accumulation of each other. In this study, we used a genetic approach to generate a model that exhibits the combined pathologies of AD and dementia with Lewy bodies (DLB). To achieve this goal, we introduced a mutant human α-synuclein transgene into 3xTg-AD mice. As occurs in human disease, transgenic mice that develop both DLB and AD pathologies (DLB-AD mice) exhibit accelerated cognitive decline associated with a dramatic enhancement of Aβ, tau, and α-synuclein pathologies. Our findings also provide additional evidence that the accumulation of α-synuclein alone can significantly disrupt cognition. Together, our data support the notion that Aβ, tau, and α-synuclein interact in vivo to promote the aggregation and accumulation of each other and accelerate cognitive dysfunction.