Miracle-dz/UniFAR-FTUs huggingface dataset:
Danirixin: A Reversible and Selective Antagonist of the CXC Chemokine Receptor 2

CXC chemokine receptor 2 (CXCR2) is a key receptor in the chemotaxis of neutrophils to sites of inflammation. The studies reported here describe the pharmacological characterization of danirixin, a CXCR2 antagonist in the diaryl urea chemical class. Danirixin has high affinity for CXCR2, with a negative log of the 50% inhibitory concentration (pIC50) of 7.9 for binding to Chinese hamster ovary cell (CHO)-expressed human CXCR2, and 78-fold selectivity over binding to CHO-expressed CXCR1. Danirixin is a competitive antagonist against CXCL8 in Ca2+-mobilization assays, with a KB (the concentration of antagonist that binds 50% of the receptor population) of 6.5 nM and antagonist potency (pA2) of 8.44, and is fully reversible in washout experiments over 180 minutes. In rat and human whole-blood studies assessing neutrophil activation by surface CD11b expression following CXCL2 (rat) or CXCL1 (human) challenge, danirixin blocks the CD11b upregulation with pIC50s of 6.05 and 6.3, respectively. Danirixin dosed orally also blocked the influx of neutrophils into the lung in vivo in rats following aerosol lipopolysaccharide or ozone challenge, with median effective doses (ED50s) of 1.4 and 16 mg/kg respectively. Thus, danirixin would be expected to block chemotaxis in disease states in which neutrophils are increased in response to inflammation, such as pulmonary diseases. In comparison with navarixin, a CXCR2 antagonist from a different chemical class, the binding characterization of danirixin is distinct. These observations may offer insight into the previously observed clinical differences in induction of neutropenia between these compounds.
Layer-encoded video in scalable adaptive streaming

Combining the concepts of caching and transmission control protocol (TCP)-friendly streaming of layer-encoded video bears the problem that those videos might not be cached in full quality. Therefore, we focus in this work on the scheduling of retransmissions of missing segments of a cached video in a manner that allows clients to receive the content in an improved quality. In a first step, we conducted subjective assessments of variations in layer-encoded video with the goal to validate existing quality metrics, including our own, which are based on certain assumptions. A statistical analysis of the subjective assessment validates these assumptions. We also show that the frequently used peak signal-to-noise ratio (PSNR) is not an appropriate metric for variations in layer-encoded video. With the insight from the subjective assessment we develop heuristics for retransmission scheduling and prove their applicability by conducting a series of simulations.
An Electrophysiological Investigation into the Role of Cognitive Control in the Attentional Blink

Accuracy at reporting a second-target (T2) is reduced if it is presented within approximately 500 ms of the first target (T1) – an attentional blink (AB). Early models explained the AB in terms of attentional limitations creating a processing bottleneck such that T2 processing would be impaired while T1 processing was ongoing. Theoretical models of the AB have more recently been expanded to include the role of cognitive control. In this dissertation I propose that cognitive control, defined as the optimization of information processing in order to achieve goals, is maladapted to the dual-task conditions of the AB task in that cognitive control optimizes the T1 goal, due to its temporal proximity, at the cost of T2. I start with the concept that the role of cognitive control is to serve goals, and that how goals are conceived of and the degree of motivation associated with those goals will determine whether cognitive control will create the condition that cause the AB. This leads to the hypothesis that electrophysiological measures of cognitive control and the degree of attentional investment resulting from cognitive control modulate the AB and explain individual differences in the AB. In a series of four studies feedback-related N2 amplitude, (reflecting individual differences in the strength of cognitive control), and event-related and resting alpha frequency oscillatory activity (reflecting degree of attentional investment), are used to explain both intraand inter-individual variability in performance on the AB task. Results supported the hypothesis that stronger cognitive control and greater attentional investment are associated with larger AB magnitudes. Attentional investment, as measured by alpha frequency oscillations, and cognitive control, as measured by the feedback-related N2, did not relate to each other as hypothesized. It is proposed that instead of a measure of attentional investment alone, alpha frequency oscillatory activity actually reflects control over information processing over time, in other words the timing of attention. With this conceptualization, various aspects of cognitive control, either related to the management of goals (feedback-related N2) or the management of attention over time to meet goals, explain variability in the AB.
ETHYL PYRUVATE PREVENTS INFLAMMATORY RESPONSES AND ORGAN DAMAGE DURING RESUSCITATION IN PORCINE HEMORRHAGE

Hemorrhage remains a common cause of death despite the recent advances in critical care, in part because conventional resuscitation fluids fail to prevent lethal inflammatory responses. Here, we analyzed whether ethyl pyruvate can provide a therapeutic anti-inflammatory potential to resuscitation fluids and prevent organ damage in porcine hemorrhage. Adult male Yorkshire swine underwent lethal hemorrhage with trauma and received no resuscitation treatment or resuscitation with Hextend alone, or supplemented with ethyl pyruvate. Resuscitation with ethyl pyruvate did not improve early hemodynamics but prevented hyperglycemia, the intrinsic coagulation pathway, serum aspartate aminotransferase, and myeloperoxidase in the major organs. Resuscitation with ethyl pyruvate provided an anti-inflammatory potential to restrain serum TNF and high-mobility group B protein 1 levels. Ethyl pyruvate inhibited nuclear factor &kgr;B in the spleen but not in the other major organs. In contrast, ethyl pyruvate inhibited NO in all the major organs, and it also inhibited TNF production in the major organs but in the lung and heart. The most significant effects were found in the terminal ileum where ethyl pyruvate inhibited cytokine production, restrained myeloperoxidase activity, preserved the intestinal epithelium, and prevented the systemic distribution of bacterial endotoxin. Ethyl pyruvate can provide therapeutic anti-inflammatory benefits to modulate splenic nuclear factor &kgr;B, restrain inflammatory responses, and prevent hyperglycemia, the intrinsic coagulation pathway, and organ injury in porcine hemorrhage without trauma.
Validation of the Chinese Version of the Quality of Nursing Work Life Scale

Quality of Nursing Work Life (QNWL) serves as a predictor of a nurse’s intent to leave and hospital nurse turnover. However, QNWL measurement tools that have been validated for use in China are lacking. The present study evaluated the construct validity of the QNWL scale in China. A cross-sectional study was conducted conveniently from June 2012 to January 2013 at five hospitals in Guangzhou, which employ 1938 nurses. The participants were asked to complete the QNWL scale and the World Health Organization Quality of Life abbreviated version (WHOQOL-BREF). A total of 1922 nurses provided the final data used for analyses. Sixty-five nurses from the first investigated division were re-measured two weeks later to assess the test-retest reliability of the scale. The internal consistency reliability of the QNWL scale was assessed using Cronbach’s α. Test-retest reliability was assessed using the intra-class correlation coefficient (ICC). Criterion-relation validity was assessed using the correlation of the total scores of the QNWL and the WHOQOL-BREF. Construct validity was assessed with the following indices: χ2 statistics and degrees of freedom; relative mean square error of approximation (RMSEA); the Akaike information criterion (AIC); the consistent Akaike information criterion (CAIC); the goodness-of-fit index (GFI); the adjusted goodness of fit index; and the comparative fit index (CFI). The findings demonstrated high internal consistency (Cronbach’s α = 0.912) and test-retest reliability (interclass correlation coefficient = 0.74) for the QNWL scale. The chi-square test (χ2 = 13879.60, df [degree of freedom] = 813 P = 0.0001) was significant. The RMSEA value was 0.091, and AIC = 1806.00, CAIC = 7730.69, CFI = 0.93, and GFI = 0.74. The correlation coefficient between the QNWL total scores and the WHOQOL-BREF total scores was 0.605 (p<0.01). The QNWL scale was reliable and valid in Chinese-speaking nurses and could be used as a clinical and research instrument for measuring work-related factors among nurses in China.
Antiproliferative effects of daucane esters from Ferula communis and F. arrigonii on human colon cancer cell lines

Certain jaesekanadiol p‐hydroxy‐ and p‐methoxybenzoates – typical of Ferula communis and Ferula arrigonii sardinian plants – show antiproliferative activity on human colon cancer less. The inhibitory doses 50%, calculated after 72 h of treatment, revealed that the antiproliferative capacity of the compounds was in the following descending order: ferutinin > 2α‐OH‐ferutidin > ferutidin > siol anisate > lapiferin > jaeskeanadiol. Evidence is presented that interaction with type II estrogen‐binding sites (EBS) underlies this activity. Copyright © 2005 John Wiley & Sons, Ltd.
Onset of expression of the variant surface glycoproteins of Trypanosoma brucei in the tsetse fly studied using immunoelectron microscopy.

The acquisition of the variant surface glycoprotein (variable antigen) coat by metacyclic stage Trypanosoma brucei in the salivary glands of the tsetse fly, Glossina morsitans, has been studied in situ by transmission and scanning electron microscopy using monoclonal antibodies raised against metacyclic variable antigen types and complexed with horseradish peroxidase or colloidal gold. The coat is acquired after binary fission has ceased but while the parasite is still attached to the gland epithelium, i.e. before the mature metacyclic is released into the gland lumen. The variable antigen type heterogeneity previously observed in discharged mature metacyclics is here demonstrated in the nascent (attached) metacyclic population. The variant surface glycoprotein genes are thus not expressed in a fixed sequence since different metacyclic variable antigen types are present ab initio. The distribution of immunogold-marked nascent metacyclics of a particular variable antigen type, as shown by quadrat analysis of a scanning electron micrograph montage of the infected salivary gland epithelium, conforms to a Poisson series. This provides evidence that individual variant surface glycoprotein genes are stochastically activated and suggests that selective activation occurs after trypanosome division has ceased.
Distributed Description Logics Revisited

Distributed Description Logics (DDLs) is a KR formalism that enables reasoning with multiple ontologies interconnected by directional semantic mapping (bridge rules). DDLs capture the idea of importing and reusing concepts between ontologies and thus combine well with intuitions behind Semantic Web. We modify the original semantics of DDLs in order to cope with a modeling discrepancy that has been pointed out in the literature. We do so by introducing a new kind of bridge rules, which we call conjunctive. Using conjunctive bridge-rules instead of the normal ones solves the problem. All the basic properties that have been established for DDLs hold also for the adjusted framework. We also provide a transformational semantics for conjunctive bridge rules, and thus, at least theoretically, a decision procedure for the new semantics.
Spanners and emulators with sublinear distance errors

Let <i>k</i> ≥ 2 be an integer. We show that any undirected and unweighted graph <i>G</i> = (<i>V, E</i>) on <i>n</i> vertices has a subgraph <i>G'</i> = (<i>V, E'</i>) with <i>O</i>(<i>kn</i><sup>1+1/<i>k</i></sup>) edges such that for any two vertices <i>u, v ∈ V</i>, if Δ<inf><i>G</i></inf>(<i>u, v</i>) = <i>d</i>, then Δ<inf><i>G'</i></inf>(<i>u, v</i>) = <i>d</i>+<i>O</i>(<i>d</i><sup>1-1/<i>k</i>-1</sup>). Furthermore, we show that such subgraphs can be constructed in <i>O</i>(<i>mn</i><sup>1/<i>k</i></sup>) time, where <i>m</i> and <i>n</i> are the number of edges and vertices in the original graph. We also show that it is possible to construct a <i>weighted</i> graph <i>G</i>* = (<i>V, E</i>*) with <i>O</i>(<i>kn</i><sup>1+1/(2<sup><i>k</i></sup>-1)</sup>) edges such that for every <i>u, v ∈ V</i>, if Δ<inf><i>G</i></inf>(<i>u, v</i>) = <i>d</i>, then Δ ≤ Δ<inf><i>G</i>*</inf>(<i>u, v</i>) = <i>d</i> + <i>O</i>(<i>d</i><sup>1-1/<i>k</i>-1</sup>). These are the first such results with additive error terms of the form <i>o</i>(<i>d</i>), i.e., additive error terms that are sublinear in the distance being approximated.
PCR-RFLP-mediated detection and speciation of bacterial species causing endophthalmitis.

PURPOSE To determine the usefulness of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in the identification and speciation of bacteria causing endophthalmitis. METHODS PCR-RFLP was performed on 53 strains of 14 bacterial species (eight Gram positive and five Gram negative) collected from both keratitis and endophthalmitis patients. Two pairs of oligonucleotide primers based on the 16S rDNA gene were used to PCR-amplify 1.2- and 1.0-kb fragments of bacterial genomic DNA. RFLPs within the PCR product were used to speciate the organisms. RESULTS The sensitivity of the nested PCR amplification reaction was one organism. All bacteria tested could be identified and speciated using RFLP analysis except for Escherichia coli and Serratia marcescens, which could not be interdifferentiated using RFLP. Molecular analysis of two vitreous samples from two eyes with typical signs of bacterial endophthalmitis confirmed the presence of E. coli in the vitreous from a culture-positive case with E. coli endophthalmitis and revealed the presence of Staphylococcus epidermidis in the vitreous of a culture-negative case. CONCLUSIONS It is expected that this technique will provide a useful laboratory tool for future microbiologic diagnosis of patients presenting with endophthalmitis, especially for those eyes that prove culture negative.
Modeling a Snap-Action, Variable-Delay Switch Controlling Extrinsic Cell Death

When exposed to tumor necrosis factor (TNF) or TNF-related apoptosis-inducing ligand (TRAIL), a closely related death ligand and investigational therapeutic, cells enter a protracted period of variable duration in which only upstream initiator caspases are active. A subsequent and sudden transition marks activation of the downstream effector caspases that rapidly dismantle the cell. Thus, extrinsic apoptosis is controlled by an unusual variable-delay, snap-action switch that enforces an unambiguous choice between life and death. To understand how the extrinsic apoptosis switch functions in quantitative terms, we constructed a mathematical model based on a mass-action representation of known reaction pathways. The model was trained against experimental data obtained by live-cell imaging, flow cytometry, and immunoblotting of cells perturbed by protein depletion and overexpression. The trained model accurately reproduces the behavior of normal and perturbed cells exposed to TRAIL, making it possible to study switching mechanisms in detail. Model analysis shows, and experiments confirm, that the duration of the delay prior to effector caspase activation is determined by initiator caspase-8 activity and the rates of other reactions lying immediately downstream of the TRAIL receptor. Sudden activation of effector caspases is achieved downstream by reactions involved in permeabilization of the mitochondrial membrane and relocalization of proteins such as Smac. We find that the pattern of interactions among Bcl-2 family members, the partitioning of Smac from its binding partner XIAP, and the mechanics of pore assembly are all critical for snap-action control.
Correction of post-stroke cognitive impairments using computer programs

article i nfo Article history: Neurorehabilitation of poststroke cognitive impairments is an important medical problem. The purpose of the present study was to estimate the efficacy of new methods of restoration of impaired cognitive functions using computer correction programs. 43 poststroke patients aged 57-69, (male — 23, female — 20) were ran- domized into two groups. First group patients have been treated with the standard methods and supplemen- tary neuropsychological computer training for 14 days, 25-35 min of duration per day. Control group received standard treatment according to Federal and local medical recommendations. Initial and achieved levels of cognitive functioning were estimated with the use of Mini Mental State Examination, Frontal Assess- ment Battery, the Clock Drawing Test, the Montreal Cognitive Assessment, Schulte's test, Hospital Anxiety and Depression Scale. We found that including the computer correction programs into the complex protocol of rehabilitation of post-stroke patients confirmed their efficacy in both clinical aspects and the Patient Global Impression Scale. Although the results are encouraging, further studies are required with larger samples and longer follow-up to identify characteristics of those patients who are most likely to benefit from computer training of cognitive functions.
A comparison of subgroups of inpatients with anorexia nervosa.

OBJECTIVE Classification of subgroups of people with anorexia nervosa has been in flux. It has not been clear whether anorexics who only purge should be grouped with pure restricters or with people who both binge and purge. METHODS We compared 27 restricting-type anorexics (RAN), 26 bulimic anorexics (BAN), and 34 restricting anorexics with purging behaviors (RAN-P). All subjects were underweight and recently admitted to a hospital. We excluded subjects who had not had a diagnosis of anorexia nervosa for at least 1 year duration. RESULTS The three groups of subjects had similar scores for Depression and Anxiety on the Beck Depression Inventory, the Spielberger State and Trait Anxiety Inventory, and on the EDI subscales aside from higher scores for BAN subjects on the Bulimia subscale. DISCUSSION These three subgroups of anorexia nervosa have similar degrees of dysphoric moods and core eating disorder symptoms when underweight and malnourished.
β2 Glycoprotein I Recognition Drives Th1 Inflammation in Atherosclerotic Plaques of Patients with Primary Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is characterized by recurrent arterial/venous thrombosis and miscarriages in the persistent presence of autoantibodies against phospholipid-binding proteins (aPLs), such as β2 glycoprotein I (β2GPI). In addition to the aPL thrombophilic effect, arterial thrombosis was related to accelerated atherosclerosis in animal models; however, contrasting findings were reported in primary APS patients with regard to the increased number of plaques or abnormal arterial wall thickness. We investigated the cytokine production induced by β2GPI in activated T cells that infiltrate in vivo atherosclerotic lesions of primary APS patients with atherothrombosis. We also examined the helper function of β2GPI-specific T cells for monocyte matrix metalloproteinase-9 and tissue factor production, as well as their cytolytic potential and their helper function for Ab production. APS patients with atherothrombosis harbor in vivo–activated CD4+ T cells that recognize β2GPI in atherothrombotic lesions. β2GPI induces T cell proliferation and IFN-γ expression in plaque-derived T cell clones. β2GPI-specific T cells display helper function for monocyte matrix metalloproteinase-9 and tissue factor production and promote Ig production in autologous B cells. Moreover, plaque-derived β2GPI-specific CD4+ T lymphocytes express perforin-mediated and Fas/Fas ligand–mediated cytotoxicity. β2GPI, and especially the DI domain, drive a local Th1 inflammatory response, with subsequent plaque instability that eventually favors atherothrombosis. This finding may explain the association between aPLs and arterial thrombosis, despite the lack of evidence of surrogate markers for atherosclerosis in primary APS.
T cells respond to heat shock protein 60 via TLR2: activation of adhesion and inhibition of chemokine receptors

Soluble 60 kDa heat shock protein (HSP60) activates macrophages via TLR4. We now report that soluble HSP60 activates T cells via the innate receptor TLR2. HSP60 activated T cell adhesion to fibronectin to a degree similar to other activators: IL‐2, SDF‐1α, and RANTES. T cell type and state of activation was important; nonactivated CD45RA+ and IL‐2‐activated CD45RO+ T cells responded optimally (1 h) at low concentrations (0.1–1 ng/ml), but nonactivated CD45RO+ T cells required higher concentrations (∼1 εg/ml) of HSP60. T cell HSP60 signaling was inhibited specifically by monoclonal antibodies (mAb) to TLR2 but not by a mAb to TLR4. Indeed, T cells from mice with mutated TLR4 could still respond to HSP60, whereas Chinese hamster T cells with mutated TLR2 did not respond. The human T cell response to soluble HSP60 depended on phosphatidylinositol 3‐kinase and protein kinase C signaling and involved the phosphorylation of Pyk‐2. Soluble HSP60 also inhibited actin polymerization and T cell chemotaxis through extracellular matrix‐like gels toward the chemokines SDF‐1α (CXCL12) or ELC (CCL19). Exposure to HSP60 for longer times (18 h) down‐regulated chemokine receptor expression: CXCR4 and CCR7. These results suggest that soluble HSP60, through TLR2‐dependent interactions, can regulate T cell behavior in inflammation.
The impact of involuntary job loss on subsequent alcohol consumption by older workers: findings from the health and retirement survey.

OBJECTIVE To estimate the effect of involuntary job loss on subsequent alcohol consumption by older workers in the United States. METHODS Using longitudinal data from the 1992 and 1994 waves of the Health and Retirement Survey, the authors estimated multivariate models to assess the impact of involuntary job loss on subsequent alcohol use. Two outcomes were investigated: reported daily alcohol consumption and onset of drinking. The analysis sample included 207 workers who experienced involuntary job loss between survey dates and a comparison group of 2,866 continuously employed workers. RESULTS After baseline alcohol consumption and a variety of socioeconomic and illness-related covariates were controlled, involuntary job loss was not associated (p>.05) with number of daily drinks consumed at follow-up. However, among those who did not consume alcohol at baseline, individuals who suffered involuntary job loss were twice as likely as continuously employed individuals to start drinking by follow-up (OR = 2.01; CI = 1.06-3.80). The majority of those who began drinking at follow-up reported drinking less than 1 drink per day. DISCUSSION The findings provide evidence of a significant relationship between job loss and subsequent alcohol use among baseline nondrinkers. However, the magnitude of the changes in drinking was quite modest.