Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms of C-Reactive Protein-Induced Blood-Brain Barrier Disruption

Background and Purpose— Increased mortality after stroke is associated with brain edema formation and high plasma levels of the acute phase reactant C-reactive protein (CRP). The aim of this study was to examine whether CRP directly affects blood-brain barrier stability and to analyze the underlying signaling pathways. Methods— We used a cell coculture model of the blood-brain barrier and the guinea pig isolated whole brain preparation. Results— We could show that CRP at clinically relevant concentrations (10 to 20 &mgr;g/mL) causes a disruption of the blood-brain barrier in both approaches. The results of our study further demonstrate CRP-induced activation of surface Fc&ggr; receptors CD16/32 followed by p38-mitogen-activated protein kinase-dependent reactive oxygen species formation by the NAD(P)H-oxidase. The resulting oxidative stress increased myosin light chain kinase activity leading to an activation of the contractile machinery. Blocking myosin light chain phosphorylation prevented the CRP-induced blood-brain barrier breakdown and the disruption of tight junctions. Conclusions— Our data identify a previously unrecognized mechanism linking CRP and brain edema formation and present a signaling pathway that offers new sites of therapeutic intervention.
Production of Reactive Oxygen Species, Alteration of Cytosolic Ascorbate Peroxidase, and Impairment of Mitochondrial Metabolism Are Early Events in Heat Shock-Induced Programmed Cell Death in Tobacco Bright-Yellow 2 Cells1

To gain some insight into the mechanisms by which plant cells die as a result of abiotic stress, we exposed tobacco (Nicotiana tabacum) Bright-Yellow 2 cells to heat shock and investigated cell survival as a function of time after heat shock induction. Heat treatment at 55°C triggered processes leading to programmed cell death (PCD) that was complete after 72 h. In the early phase, cells undergoing PCD showed an immediate burst in hydrogen peroxide (H2O2) and superoxide (O2·-) anion production. Consistently, death was prevented by the antioxidants ascorbate (ASC) and superoxide dismutase (SOD). Actinomycin D and cycloheximide, inhibitors of transcription and translation, respectively, also prevented cell death, but with a lower efficiency. Induction of PCD resulted in gradual oxidation of endogenous ASC; this was accompanied by a decrease in both the amount and the specific activity of the cytosolic ASC peroxidase (cAPX). A reduction in cAPX gene expression was also found in the late PCD phase. Moreover, changes of cAPX kinetic properties were found in PCD cells. Production of ROS in PCD cells was accompanied by early inhibition of glucose (Glc) oxidation, with a strong impairment of mitochondrial function as shown by an increase in cellular NAD(P)H fluorescence, and by failure of mitochondria isolated from cells undergoing PCD to generate membrane potential and to oxidize succinate in a manner controlled by ADP. Thus, we propose that in the early phase of tobacco Bright-Yellow 2 cell PCD, ROS production occurs, perhaps because of damage of the cell antioxidant system, with impairment of the mitochondrial oxidative phosphorylation.
Health Impact Assessment of Environmental Tobacco Smoke in European Children: Sudden Infant Death Syndrome and Asthma Episodes

478  Public Health Reports / May–June / Volume 125 This article by Boldo et al. demonstrates that in Europe, exposure to environmental tobacco smoke (ETS) caused an estimated 24% to 32% of sudden infant death syndrome (SIDS) cases and increased the number of asthma episodes by 7% to 11% in children younger than 14 years of age. The major source of exposure to ETS among children is smoking by parents and other household members. The European countries in this study included wealthy countries such as Austria, Denmark, Germany, and the United Kingdom as well as those with struggling economies such as Bulgaria, Croatia, Estonia, and Macedonia. This diversity of wealth across the 27 countries included in the study provided a range of exposures when correlated with the smoking rates. The levels of exposure to ETS for the children in the study ranged from one-fifth to one-half. Using the data from the 27 countries and applying the methods used by others to look at the association of ETS to both SIDS and asthma, the authors make a compelling case for recommending to governmental and ministerial officials that their countries follow the World Health Organization (WHO) recommendations to develop and implement enforceable smoke-free policies to avoid the ETS impact on children’s health. Such a recommendation is logical, progressive, and highly protective of the most vulnerable members of the population.1 This study also demonstrates the need for countries, as well as WHO and the European Union, to develop educational programs for parents and children to recognize the dangers of smoking, ETS, and other tobacco-related diseases.
First-line chemotherapy with docetaxel plus capecitabine followed by capecitabine or hormone maintenance therapy for the treatment of metastatic breast cancer patients

The primary aim of the present study was to evaluate whether maintenance therapy with capecitabine or hormone replacement therapy (HRT) results in improved progression-free survival (PFS) in metastatic breast cancer (MBC) patients who had previously achieved disease control with first-line docetaxel plus capecitabine (TX) chemotherapy. Seventy-nine metastatic breast cancer patients treated between January 2008 and June 2013 with TX chemotherapy were retrospectively analyzed. Following successful initial disease control by the combination chemotherapy, 39 patients received single-agent capecitabine maintenance therapy and 40 patients received HRT as maintenance therapy. The PFS time, objective response rate, clinical benefit rate and safety of the two groups were compared. The median PFS of the total cohort (n=79) was 11.0 months. Furthermore, the median PFS time of the capecitabine (n=39) and HRT groups (n=40) were 10.9 and 11.1 months, respectively (P=0.283). Compared with the PFS time of maintenance treatment only, single-agent capecitabine treatment following TX chemotherapy prolonged the PFS time by 6.8 months and HRT following TX chemotherapy prolonged PFS time by 5.8 months (P=0.551). Of the total cohort, 49 patients did not receive palliative endocrine therapy prior to chemotherapy, including 22 patients in the capecitabine maintenance group and 27 patients in the HRT maintenance group. The PFS time from the commencement of maintenance treatment was significantly different between the two groups, 6.1 months in the capecitabine group compared with 11.5 months in the HRT group (P=0.045). For the 30 patients who underwent palliative endocrine therapy prior to TX chemotherapy, the PFS times of the capecitabine and HRT maintenance treatment groups were 7.5 and 4.1 months, respectively (P=0.043). However, the occurrence of adverse events, such as hematological and gastrointestinal toxicity, as well as hand-foot syndrome, were not significantly different between the two groups. The current study indicated that single-agent capecitabine maintenance therapy may be a potential treatment strategy for MBC patients who responded to capecitabine-based chemotherapy. In particular, capecitabine may provide a more effective maintenance treatment duration compared with HRT for patients who had previously undergone first-line palliative HRT for MBC.
Interactive role of human immunodeficiency virus type 1 (HIV-1) clade-specific Tat protein and cocaine in blood-brain barrier dysfunction: Implications for HIV-1-associated neurocognitive disorder

In recent years, increasing interest has emerged to assess the human immunodeficiency virus type 1 (HIV-1) clade C viral pathogenesis due to its anticipated spread in the United States and other western countries. Previous studies suggest that clade C is less neuropathogenic than clade B; however, the underlying mechanism is poorly understood. Additionally, the interactive role of drugs of abuse such as cocaine on clade C-associated neuropathogenesis has not been reported. In the current study, we hypothesize that HIV-1 clade-specific Tat proteins exert differential effects on blood-brain barrier (BBB) integrity and cocaine further differentially aggravates the BBB dysfunction. We evaluated the effect of Tat B and Tat C and/or cocaine on the BBB integrity using an in vitro model constructed with primary human brain microvascular endothelial cells (HBMECs) and astrocytes. The BBB membrane integrity was measured by transendothelial electrical resistance (TEER) and paracellular permeability was measured by fluorescein isothiocyanate (FITC)-dextran transport assay and monocytes transmigration across the BBB. Results indicate that Tat B disrupts BBB integrity to a greater extent compared to Tat C and cocaine further differentially exacerbates the BBB dysfunction. This BBB dysfunction was associated with altered expression of tight junction proteins zona occuldens (ZO-1) and junctional adhesion molecule (JAM)-2. Thus, these results for the first time delineate the differential role of Tat B and Tat C and/or cocaine in BBB dysfunction, which may be correlated with the clade-specific differences observed in HIV-1-associated neurological disorders.
Adaptive foreground segmentation using fuzzy approach

In this paper, we propose a simple and novel method for background modeling and foreground segmentation for visual surveillance applications. This method employs histogram based median method using HSV color space and a fuzzy k-means clustering. A histogram for each pixel among the training frames is constructed first, then the highest bin of the histogram is chosen and the median value among this bin is selected as the estimated value of background model for this pixel. A background model is established after the above procedure is applied to all the pixels. Fuzzy k-means clustering is used to classify each pixel in current frame either as the background pixel or the foreground pixel. Experimental results on a set of indoor videos show the effectiveness of the proposed method. Compared with other two contemporary methods — k-means clustering and Mixture of Gaussians (MoG) — the proposed method is not only time efficient but also provides better segmentation results.
Power in Negotiated and Reciprocal Exchange

While classical exchange theorists excluded bargaining from the scope of their theories, most contemporary theorists have done the opposite, concentrating exclusively on negotiated exchanges with binding agreements. We analyze how the form of social exchange—negotiated or reciprocal—affects the distribution of power in exchange networks. These two forms of exchange differ in fundamental ways that affect how actors use power and the kinds of risk and uncertainty they face. We predict that these basic differences will affect the relation between the availability of alternative partners and actors’ use of power, and will produce lower power use in reciprocal exchange than in negotiated exchange. We test our predictions in a laboratory experiment. The results support the underlying logic of our theory, partially support its specific predictions, and raise new questions about the importance of the different time perspectives required by negotiated and reciprocal exchange.
Potato Consumption and Risk of Type 2 Diabetes: Results From Three Prospective Cohort Studies

OBJECTIVE We aimed to elucidate whether potato consumption is associated with a higher risk of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS We analyzed data in three cohorts consisting of U.S. male and female health professionals without diabetes, cardiovascular disease, and cancer at baseline: 70,773 women from the Nurses’ Health Study (1984–2010), 87,739 women from Nurses’ Health Study II (1991–2011), and 40,669 men from the Health Professionals Follow-up Study (1986–2010). Potato consumption was assessed quadrennially using validated food frequency questionnaires (FFQs), and we calculated 4-year change in potato consumption from consecutive FFQs. Self-reported T2D diagnosis was confirmed using a validated supplementary questionnaire. RESULTS During 3,988,007 person-years of follow-up, 15,362 new cases of T2D were identified. Higher consumption of total potatoes (including baked, boiled, or mashed potatoes and french fries) was significantly associated with an elevated risk for T2D: the pooled hazard ratio (HR) of T2D compared with <1 serving/week was 1.07 (95% CI 0.97–1.18) for 2–4 servings/week and 1.33 (95% CI 1.17–1.52) for ≥7 servings/week after adjustment for demographic, lifestyle, and dietary factors. In addition, the pooled HRs of T2D for every 3 servings/week were 1.04 (95% CI 1.01–1.08) for baked, boiled, or mashed potatoes, and 1.19 (95% CI 1.13–1.25) for french fries. We further estimated that the HR of T2D was 0.88 (95% CI 0.84–0.91) for replacing 3 servings/week of total potatoes with the same amount of whole grains. Last, in comparison with stable potato consumption, every 3-servings/week increment of potato consumption in 4 years was associated with a 4% (95% CI 0–8%) higher T2D risk. CONCLUSIONS Greater consumption of potatoes, especially french fries, was associated with a higher T2D risk, independent of BMI and other risk factors. Replacement of potatoes with whole grains was associated with a lower T2D risk.
In vivo evidence that secretion of HLA‐G by immunogenic tumor cells allows their evasion from immunosurveillance

Human leukocyte antigen‐G (HLA‐G) expression by tumors has been evidenced in numerous malignancies in association with poor prognosis and resistance to immunotherapy in humans. Particularly, soluble form of HLA‐G was measured at high concentrations in malignant effusions and plasma from cancer patients, and inhibits antitumor immune cells in vitro through interaction with immunoglobulin‐like transcript (ILT) receptors. Nevertheless, in vivo study demonstrating that HLA‐G secretion by tumor cells allows their escape from immunosurveillance remained to be established. Despite nondescribed murine homolog, direct functional interaction of HLA‐G with murine paired immunoglobulin‐like receptor (PIR)‐B, ortholog of human ILT receptors, enables to investigate its role in vivo. Immunocompetent mice were injected either with syngeneic tumor cells co‐expressing HLA‐G5, the main soluble HLA‐G isoform, and the conformation stabilizer human β2‐microglubulin (hβ2m), or with hβ2m+HLA‐G5− tumor cells. hβ2m expressed at both tumor cell surface acted as a tumor antigen triggering a specific humoral response. Interestingly, although hβ2m+HLA‐G5− tumors were rejected, secreted HLA‐G5 provided hβ2m+HLA‐G5+ tumors a protection against hβ2m‐elicited immune rejection, enabling such immunogenic tumors to grow similarly to a poorly immunogenic tumor. HLA‐G5 tumor expression was associated with local and peripheral immunosuppression, characterized by dampened anti‐hβ2m B‐cell response, quantitative and functional T‐and B‐cell defects, accumulation of myeloid‐derived suppressor cells able to inhibit T‐cell proliferation and reduced T‐ and B‐cell tumor infiltrate. Our study provides the first in vivo proof that soluble HLA‐G counteracts tumor rejection and reinforces the importance to consider HLA‐G as a promising target to optimize current cancer immunotherapies.
Major complications of tibial tuberosity advancement in 1613 dogs

Objectives: To report major postoperative complications in 1613 dogs with tibial tuberosity advancement (TTA). Study design: Retrospective case series. Sample population: Dogs (n = 1613) with cranial cruciate ligament deficiency treated with TTA. Methods: Medical records of TTAs performed between December 2007‐2013 were reviewed for age, sex, weight, contralateral stifle surgery, surgical approach, duration of preoperative lameness, presence of meniscal damage, concurrent patellar luxation and simultaneous bilateral TTA. Major postoperative complications were defined as surgical site infection (SSI) (superficial, deep, or organ/space), implant failure, fracture, patellar luxation, and meniscal tear. Results: Major complications were recorded in 13.4% of cases. Superficial SSI (incisional irritation) was diagnosed in 6.9% cases, requiring only antimicrobial therapy. Other complications included postliminary medial meniscal tear (2% incidence), deep SSI (incisional dehiscence, 1.1%), implant failure (1%), patellar luxation (1.2%), fracture (0.9%), and organ/space SSI (septic arthritis, 0.4%). Dogs with normal menisci were less likely to develop postliminary meniscal tears if the medial meniscus was released at the time of TTA (P < .0001). No association was detected between recorded parameters and complications, although dogs >8 years old approached significance (P = .05) in terms of predisposition to major complications. Conclusions: Major complications after TTA are uncommon, even in dogs with concurrent patellar luxation or bilateral simultaneous procedures. In spite of its morbidity, medial meniscal release may prevent postliminary meniscal tears.
Program Synthesis Using Natural Language

Interacting with computers is a ubiquitous activity for millions of people. Repetitive or specialized tasks often require creation of small, often one-off, programs. End-users struggle with learning and using the myriad of domain-specific languages (DSLs) to effectively accomplish these tasks. We present a general framework for constructing program synthesizers that take natural language (NL) inputs and produce expressions in a target DSL. The framework takes as input a DSL definition and training data consisting of NL/DSL pairs. From these it constructs a synthesizer by learning optimal weights and classifiers (using NLP features) that rank the outputs of a keyword-programming based translation. We applied our framework to three domains: repetitive text editing, an intelligent tutoring system, and flight information queries. On 1200+ English descriptions, the respective synthesizers rank the desired program as the top-1 and top-3 for 80% and 90% descriptions respectively.
Software reliability

In this article, we present an overview of the state of the art in software reliability. We present some of the traditional software reliability models as well as recent advances in modeling. In so doing, we discuss use of hidden Markov models, as well as nonparametric models including mixtures of Dirichlet processes. Furthermore, we review decision problems in software reliability such as testing strategies and optimal stopping rules. We discuss computational issues associated with use of the models, their statistical analyses and development of optimal strategies. WIREs Comp Stat 2011 3 269–281 DOI: 10.1002/wics.159
Association of the Type 2 Diabetes Mellitus Susceptibility Gene, TCF7L2, with Schizophrenia in an Arab-Israeli Family Sample

Many reports in different populations have demonstrated linkage of the 10q24–q26 region to schizophrenia, thus encouraging further analysis of this locus for detection of specific schizophrenia genes. Our group previously reported linkage of the 10q24–q26 region to schizophrenia in a unique, homogeneous sample of Arab-Israeli families with multiple schizophrenia-affected individuals, under a dominant model of inheritance. To further explore this candidate region and identify specific susceptibility variants within it, we performed re-analysis of the 10q24-26 genotype data, taken from our previous genome-wide association study (GWAS) (Alkelai et al, 2011). We analyzed 2089 SNPs in an extended sample of 57 Arab Israeli families (189 genotyped individuals), under the dominant model of inheritance, which best fits this locus according to previously performed MOD score analysis. We found significant association with schizophrenia of the TCF7L2 gene intronic SNP, rs12573128, (p = 7.01×10−6) and of the nearby intergenic SNP, rs1033772, (p = 6.59×10−6) which is positioned between TCF7L2 and HABP2. TCF7L2 is one of the best confirmed susceptibility genes for type 2 diabetes (T2D) among different ethnic groups, has a role in pancreatic beta cell function and may contribute to the comorbidity of schizophrenia and T2D. These preliminary results independently support previous findings regarding a possible role of TCF7L2 in susceptibility to schizophrenia, and strengthen the importance of integrating linkage analysis models of inheritance while performing association analyses in regions of interest. Further validation studies in additional populations are required.
Adaptive-passive control of vibration transmission in beams using electro/magnetorheological fluid filled inserts

A method for the control of the transmission of bending vibrations in beams is described. A composite beam (a structural insert) is inserted into a part of the structure to affect the transmission there. The insert comprises two elastic face plates and a central core of tunable fluid such as an electrorheological (ER) or magnetorheological (MR) fluid. By adjusting the applied electric or magnetic field the theological properties of the fluid can be controlled and so can the vibration transmission properties of the insert. Theoretical results concerning the transmission of vibrations in beam-like structures are reviewed. Numerical results are presented for the transmission through ER and MR fluid filled inserts, with experimental results for an ER case. The transmission is seen to show a pass/stopband structure with the stopbands being tunable.
Britain and Europe

would be foolish to attempt to discuss Britain's relationship with the countries of Continental Europe without making some quick glance back at the history of the last ten years; oversimplified as the resulting picture will be, the oversimplification in itself is revealing. Politically, the ten years fall into three periods, the first the thirty months that ended with the Communist coup d'etat in Czechoslovakia and the Berlin Blockade, the second the period of fear and uncertainty between 1948 and 1950, the third that which began four months after the invasion of South Korea with M. Rene Pleven's proposal for a European Army. The climax to that period was the EDC treaty; the anti-climax, the rejection of the whole project by the French National Assembly in August, 1954. Yet, while the story of the treaty is one of a descending curve of hope and interest, two other events diluted the feelings of increasing despondency. One was the death of Stalin, the other the negotiations for the treaty that replaced EDC, for out of that came a definite committment by the United Kingdom Government to be concerned in the supervision and control of German rearmament. From all points of view that period ended with the meeting this summer of the four leaders at Geneva, and in its way that conference typified the whole ten years. It broke up with an exchange of admirable sentiments and it left all the problems of German reunification unsettled, and shelved for someone else to discuss later.
Ultrastructural organization of the sensory fibers innervating the Golgi tendon organ

The organization of the sensory innervation of Golgi tendon organs (GTO) from E. carpi ulnaris of the cat is described. The large Ib afferent fiber gives rise to small myelinated branches which become oriented longitudinally in a neural compartment of the GTO capsule lumen. The latter give rise to smaller, unmyelinated branches which further arborize among loosely packed collagen bundles. The unmyelinated fibers form numerous varicosities and small terminal branches which have portions of the axolemma covered only by basal lamina which intervenes between the collagen bundles and the axolemma. In places, the axon's surface may lack all investments and nerve and collagen come into intimate association. The large unmyelinated branches and their varicosities have different axoplasmic characteristics compared with the small unmyelinated terminal portions. The latter contain few or no mitochondria, vesicles, neurotubules, and neurofilaments. In addition to the description of the terminals, the similarities and differences of the innervation of the GTO, compared with other mechanoreceptors, are discussed.