Miracle-dz/UniFAR-FTUs huggingface dataset:
Frontline: Characterization of BT3 molecules belonging to the B7 family expressed on immune cells

New members of the B7 family have been recently described as regulators of T cell activation and function. Butyrophilin (BT) has also been related to the B7 family by sequence similarity analyses. We present a new subfamily called BT3, which belongs to the B7/BT family. The BT3 subfamily comprises three members (BT3.1, .2 and .3) that exhibit 95% identity and form a monophylogenetic group along with the BT‐related members. High expression levels of BT3 transcripts were detected in lymphoid tissues (mainly spleen, lymph node and PBL). Using anti‐BT3 mAb we could demonstrate BT3 expression on immune cells including T, B and NK cells, monocytes and dendritic cells as well as hematopoietic precursors and some tumor cell lines. As described earlier for PDL‐1 and ICOS‐L, BT3 molecules are expressed on endothelial cells and up‐regulated upon activation by IFN‐γ or TNF‐α. The BT3.1 counter‐receptor (BT3.1‐R) was analyzed by means of binding experiments using BT3.1‐Ig soluble protein. The BT3.1‐R is not CD28, CTLA‐4, ICOS, PD‐1 or BTLA and seems restricted to some T cell and hematopoietic cell lines. Altogether, these data describe new members of the B7/BT family that may play a role in regulation of the immune response.
Social networks in software process improvement

Software process improvement in small organisation is often problematic and communication and knowledge sharing is more informal. To improve software processes we need to understand how they communicate and share knowledge. In this article have studied the company SmallSoft through action research. In the action research we have applied the framework of social network analysis and we show this can be used to understand the underlying structures of communication and knowledge sharing between software developers and managers. We show in detail how the analysis can be done and how the management can utilise the ﬁndings. From this we conclude that social network analysis was a useful framework together with accompanying tools and techniques. Copyright  2009 John Wiley & Sons, Ltd.
Fast detection of node mergers using logic implications

In this paper, we propose a new node merging algorithm using logic implications. The proposed algorithm only requires two logic implications to find the substitute nodes for a given target node, and thus can efficiently detect node mergers. Furthermore, we also apply the node merger identification algorithm for area optimization in VLSI circuits. We conduct experiments on a set of IWLS 2005 benchmarks. The experimental results show that our algorithm has a competitive capability on area optimization compared to a global observability don't care (ODC)-based node merging algorithm which is highly time-consuming. Our speedup is approximately 86 times for overall benchmarks. Categories and Subject Descriptors B.6. 3 [Logic Design]: Design Aids-Optimization General Terms Algorithms
Identification of Therapeutic Covariant MicroRNA Clusters in Hypoxia-Treated Cardiac Progenitor Cell Exosomes Using Systems Biology

Rationale: Myocardial infarction is a leading cause of death in developed nations, and there remains a need for cardiac therapeutic systems that mitigate tissue damage. Cardiac progenitor cells (CPCs) and other stem cell types are attractive candidates for treatment of myocardial infarction; however, the benefit of these cells may be as a result of paracrine effects. Objective: We tested the hypothesis that CPCs secrete proregenerative exosomes in response to hypoxic conditions. Methods and Results: The angiogenic and antifibrotic potential of secreted exosomes on cardiac endothelial cells and cardiac fibroblasts were assessed. We found that CPC exosomes secreted in response to hypoxia enhanced tube formation of endothelial cells and decreased profibrotic gene expression in TGF-&bgr;–stimulated fibroblasts, indicating that these exosomes possess therapeutic potential. Microarray analysis of exosomes secreted by hypoxic CPCs identified 11 miRNAs that were upregulated compared with exosomes secreted by CPCs grown under normoxic conditions. Principle component analysis was performed to identify miRNAs that were coregulated in response to distinct exosome-generating conditions. To investigate the cue–signal–response relationships of these miRNA clusters with a physiological outcome of tube formation or fibrotic gene expression, partial least squares regression analysis was applied. The importance of each up- or downregulated miRNA on physiological outcomes was determined. Finally, to validate the model, we delivered exosomes after ischemia–reperfusion injury. Exosomes from hypoxic CPCs improved cardiac function and reduced fibrosis. Conclusions: These data provide a foundation for subsequent research of the use of exosomal miRNA and systems biology as therapeutic strategies for the damaged heart.
Comprehensive management of dysfunctional voiding.

OBJECTIVE Dysfunctional voiding is a major problem leading to daytime-wetting and recurrent urinary tract infection (UTI). Our center is devoted to treating children with dysfunctional voiding. We offer a multidisciplinary approach with a pediatric nephrologist, nurse practitioners, and a psychologist. This article is the first to describe the efficacy of this approach on a large population of American children. PATIENTS Between 1992 and 1995, 366 children with symptoms of voiding dysfunction were referred for urodynamic studies. Criteria were based on the child's age, symptoms, and failure to respond to empirical therapy. Females made up 77% of the population, and the mean age at referral was 8.5 years (range, 4 to 18 years). Day-wetting occurred in 312 (89%), night-wetting in 278 (79%), recurrent UTI in 218 (60%), and vesicoureteral reflux (VUR) in 48 (20%) of those undergoing voiding cystourethrography. RESULTS A minimum of 6 months' follow-up data (mean, 22 months) is available on 280 children (77% studied). Urge syndrome was the predominant urodynamic finding in 52%, followed by bladder sphincter dysfunction in 25%. Treatment consisted of antibiotic prophylaxis (59%), anticholinergic medication (49%), biofeedback (25%), and psychological counseling (15%). Of the 222 children with daytime-wetting (45%), 100 are cured (off all medication, no wetting) and 82 (37%) are improved (on medication or >50% reduction in symptoms). Improvement or cure was seen in 69% of children with night-wetting. Of the 199 children with UTI, 127 (64%) never developed another infection. Vesicoureteral reflux resolved in 16 of 30 (53%) children undergoing repeat voiding cystourethrography. CONCLUSION Our comprehensive approach demonstrates a favorable outcome that promises to reduce the medical and psychological morbidity seen in patients with voiding dysfunction.
Circle-based eye center localization (CECL)

The ability to automatically detect eye center locations in video images allows for estimating gaze direction. This, in turn, facilitates the study of human-computer interaction and behavioral analyses of social interactions. We propose an improved eye center localization method based on the Hough transform, called Circle-based Eye Center Localization (CECL) that is simple, robust, and achieves accuracy at a par with typically more complex state-of-the-art methods. The CECL method relies on color and shape cues that distinguish the iris from other facial structures. The circle enclosing the iris is localized by means of the Hough transform and the center of the iris is determined using the intensity level within the detected circle. The accuracy of the CECL method is demonstrated through a comparison with 15 state-of-the-art eye center localization methods against five error thresholds, as reported in the literature. The CECL method achieved an accuracy of 80.8% to 99.4% and ranked first for 2 of the 5 thresholds. It is concluded that the CECL method offers an attractive alternative to existing methods for automatic eye center localization.
The 18 kDa Translocator Protein (Peripheral Benzodiazepine Receptor) Expression in the Bone of Normal, Osteoprotegerin or Low Calcium Diet Treated Mice

The presence of the translocator protein (TSPO), previously named as the mitochondrial or peripheral benzodiazepine receptor, in bone cells was studied in vitro and in situ using RT-qPCR, and receptor autoradiography using the selective TSPO ligand PK11195. In vitro, the TSPO is highly expressed in osteoblastic and osteoclastic cells. In situ, constitutive expression of TSPO is found in bone marrow and trabecular bone, e.g., spongiosa. Mice with a reduction of bone turnover induced by a 4-day treatment of osteoprotegerin reduces [3H]PK11195 binding in the spongiosa (320±128 Bq.mg−1, 499±106 Bq.mg−1 in saline-treated controls). In contrast, mice with an increase in bone turnover caused by a 4-day low calcium diet increases [3H]PK11195 binding in the spongiosa (615±90 Bq.mg−1). Further, our study includes technical feasibility data on [18F]fluoride microPET imaging of rodent bone with altered turnover. Despite [18F]fluoride having high uptake, the in vivo signal differences were small. Using a phantom model, we describe the spillover effect and partial volume loss that affect the quantitative microPET imaging of the small bone structures in experimental mouse models. In summary, we demonstrate the expression of TSPO in small rodent bone tissues, including osteoblasts and osteoclasts. A trend increase in TSPO expression was observed in the spongiosa from low to high bone turnover conditions. However, despite the potential utility of TSPO expression as an in vivo biomarker of bone turnover in experimental rodent models, our small animal PET imaging data using [18F]fluoride show that even under the condition of a good biological signal-to-noise ratio and high tracer uptake, the currently achievable instrument sensitivity and spatial resolution is unlikely to be sufficient to detect subtle differences in small structures, such as mouse bone.
Isoflurane Enhances Both Fast and Slow Synaptic Inhibition in the Hippocampus at Amnestic Concentrations

Background: Inhibition mediated by &ggr;-aminobutyric acid type A (GABAA) receptors has long been considered an important target for a variety of general anesthetics. In the hippocampus, two types of phasic GABAA receptor-mediated inhibition coexist: GABAA,fast, which is expressed primarily at peri-somatic sites, and GABAA,slow, which is expressed primarily in the dendrites. Their spatial segregation suggests distinct functions: GABAA,slow may control plasticity of dendritic synapses, whereas GABAA,fast controls action potential initiation at the soma. We examined modulation of GABAA,fast and GABAA,slow inhibition by isoflurane at amnesic concentrations, and compared it with modulation by behaviorally equivalent doses of the GABAA receptor-selective drug etomidate. Methods: Whole cell recordings were obtained from pyramidal cells in organotypic hippocampal cultures prepared from C57BL/6 × 129/SvJ F1 hybrid mice. GABAA receptor-mediated currents were isolated using glutamate receptor antagonists. GABAA,slow currents were evoked by electrical stimulation in the stratum lacunosum-moleculare. Miniature GABAA,fast currents were recorded in the presence of tetrodotoxin. Results: 100 &mgr;M isoflurane (approximately EC50,amnesia) slowed fast- and slow-inhibitory postsynaptic current decay by approximately 25%. Higher concentrations, up to 400 &mgr;M, produced proportionally greater effects without altering current amplitudes. The effects on GABAA,slow were approximately one-half those produced by equi-amnesic concentrations of etomidate. Conclusions: Isoflurane enhances both types of phasic GABAA receptor-mediated inhibition to similar degrees at amnesic concentrations. This pattern differs from etomidate, which at low concentrations selectively enhances slow inhibition. These effects of isoflurane are sufficiently large that they may contribute substantially to its suppression of hippocampal learning and memory.
Significance of coagulase-negative Staphylococcus in urine.

Twenty-six episodes of urinary-tract infection due to coagulase-negative Staphylococci were studied. These represented 16.7% of all urinary-tract infections seen in one clinic over a 21-month period. Some seasonal variation was observed. Some patients were asymptomatic; others had acute pyelonephritis, isolated loin pain or symptoms referable to the lower urinary tract. Coagulase-negative staphylococci frequently multiply in the urinary tract in numbers less than 100,000 per ml; for this reason a careful bacteriologic assessment is essential. To make a rapid diagnosis without use of quantitative bacteriology on multiple voided specimens, it is preferable to obtain urine for culture by the technique of suprapubic bladder aspiration. It is suggested that women infected with this organism should have their urinary tract investigated radiologically at the time of initial presentation.
Non-homogeneous conduction in giant axons of the nerve cord of Periplaneta americana.

Studies with intracellular electrodes show that the abdominal giant axons of the cockroach give ascending responses to stimulation of cercal nerves and descending responses to stimulation of S 0 -T 1 connectives. 2. In the thoracic region one or more areas of low safety factors occur for descending conduction. 3. These areas, which are considered not to be synapses, are blocked by low doses of nicotine (2-5 µg./ml.) fatigued by repetitive stimulation and show conduction delays of 0·6-0·7 msec. 4. It is concluded that the abdominal giant axons extend continuously from A 6 to suboesophageal ganglion. The possibility of bi-directional conduction under physiological conditions is discussed.
TRIP‐Br: a novel family of PHD zinc finger‐ and bromodomain‐interacting proteins that regulate the transcriptional activity of E2F‐1/DP‐1

We report the isolation of TRIP‐Br1, a transcriptional regulator that interacts with the PHD‐bromodomain of co‐repressors of Krüppel‐associated box (KRAB)‐mediated repression, KRIP‐1(TIF1β) and TIF1α, as well as the co‐activator/adaptor p300/CBP. TRIP‐Br1 and the related protein TRIP‐Br2 possess transactivation domains. Like MDM2, which has a homologous transactivation domain, TRIP‐Br proteins functionally contact DP‐1, stimulating E2F‐1/DP‐1 transcriptional activity. KRIP‐1 potentiates TRIP‐Br protein co‐activation of E2F‐1/DP‐1. TRIP‐Br1 is a component of a multiprotein complex containing E2F‐1 and DP‐1. Co‐expression of the retinoblastoma gene product (RB) abolishes baseline E2F‐1/DP‐1 transcriptional activity as well as TRIP‐Br/KRIP‐1 co‐activation, both of which are restored by the adenovirus E1A oncoprotein. These features suggest that TRIP‐Br proteins function at E2F‐responsive promoters to integrate signals provided by PHD‐ and/or bromodomain‐ containing transcription factors. TRIP‐Br1 is identical to the cyclin‐dependent kinase 4 (cdk4)‐binding protein p34SEI‐1, which renders the activity of cyclin D/cdk4 resistant to the inhibitory effect of p16INK4a during late G1. TRIP‐Br1(p34SEI‐1) is differentially overexpressed during the G1 and S phases of the cell cycle, consistent with a dual role for TRIP‐Br1(p34SEI‐1) in the regulation of cell cycle progression through sequential effects on the transcriptional activity of E2F‐responsive promoters during G1 and S phases.
The Prognostic Value of p16 Hypermethylation in Cancer: A Meta-Analysis

Background The prognostic value of p16 promoter hypermethylation in cancers has been evaluated for several years while the results remain controversial. We thus performed a systematic review and meta-analysis of studies assessing the impact of p16 methylation on overall survival (OS) and disease-free survival (DFS) to clarify this issue. Methods We searched Pubmed, Embase and ISI web of knowledge to identify studies on the prognostic impact of p16 hypermethylation in cancers. A total of 6589 patients from 45 eligible studies were included in the analysis. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to estimate the effect using random-effects model. Results The analysis indicated that p16 hypermethylation had significant association with poor OS of non-small cell lung cancer (NSCLC) (HR 1.74, 95% CI: 1.36–2.22) and colorectal cancer (CRC) (HR 1.80; 95% CI 1.27–2.55). Moreover, the significant correlation was present between p16 hypermethylation and DFS of NSCLC (HR 2.04, 95% CI: 1.19–3.50) and head and neck cancer (HR 2.24, 95% CI: 1.35–3.73). Additionally, in the analysis of the studies following REMARK guidelines more rigorously, p16 hypermethylation had unfavorable impact on OS of NSCLC (HR 1.79, 95% CI: 1.35–2.39) and CRC (HR 1.96, 1.16–3.34), and on DFS of NSCLC (HR 2.12, 95% CI: 1.21–3.72) and head and neck cancer (HR 2.24, 95% CI: 1.35–3.73). Conclusions p16 hypermethylation might be a predictive factor of poor prognosis in some surgically treated cancers, particularly in NSCLC.
Subtle Scientific Fallacies Undermine the Validity of Neuroendocrinological Research: Do Not Draw Premature Conclusions on the Role of Female Sex Hormones

Major scientific flaws such as reporting and publication biases are well documented, even though acknowledgment of their importance appears to be lacking in various psychological and medical fields. Subtle and less obvious biases including selective reviews of the literature and empirically unsupported conclusions and recommendations have received even less attention. Using the literature on the association between transition to menopause, hormones and the onset of depression as a guiding example, I outline how such scientific fallacies undermine the validity of neuroendocrinological research. It is shown that in contrast to prominent claims, first, most prospective studies do not support the notion that the menopausal transition relates to increased risk for depression, second, that associations between hormone levels and depression are largely inconsistent and irreproducible, and, third, that the evidence for the efficacy of hormone therapy for the treatment of depression is very weak and at best inconclusive. I conclude that a direct and uniform association between female sex hormones and depression is clearly not supported by the literature and that more attention should be paid to the manifold scientific biases that undermine the validity of findings in psychological and medical research, with a specific focus on the behavioral neurosciences.
Charge transfer and transport in DNA.

We explore charge migration in DNA, advancing two distinct mechanisms of charge separation in a donor (d)-bridge ([Bj])-acceptor (a) system, where [Bj] = B1,B2, . , BN are the N-specific adjacent bases of B-DNA: (i) two-center unistep superexchange induced charge transfer, d*[Bj]a --> d[Bj]a+/-, and (ii) multistep charge transport involves charge injection from d* (or d+) to [Bj], charge hopping within [Bj], and charge trapping by a. For off-resonance coupling, mechanism i prevails with the charge separation rate and yield exhibiting an exponential dependence approximately exp(-betaR) on the d-a distance (R). Resonance coupling results in mechanism ii with the charge separation lifetime tau approximately Neta and yield Y approximately (1 + Neta)-1 exhibiting a weak (algebraic) N and distance dependence. The power parameter eta is determined by charge hopping random walk. Energetic control of the charge migration mechanism is exerted by the energetics of the ion pair state dB1+/-B2 . BNa relative to the electronically excited donor doorway state d*B1B2 . BNa. The realization of charge separation via superexchange or hopping is determined by the base sequence within the bridge. Our energetic-dynamic relations, in conjunction with the energetic data for d*/d- and for B/B+, determine the realization of the two distinct mechanisms in different hole donor systems, establishing the conditions for "chemistry at a distance" after charge transport in DNA. The energetic control of the charge migration mechanisms attained by the sequence specificity of the bridge is universal for large molecular-scale systems, for proteins, and for DNA.
Quantitative Computed Tomography Measurement of Tracheal Cross-Sectional Areas in Relapsing Polychondritis: Correlations with Spirometric Values

Background: Although tracheal stenosis occurs in relapsing polychondritis (RP), no studies exist that have clarified correlations between quantitative airway measurement and spirometry in RP patients. Objectives: The aim of this study was to investigate correlations between the cross-sectional area (CSA) of the trachea and spirometric values in patients with RP. Methods: The institutional review board approved this retrospective study, and written informed consent was waived. Twenty-six patients with RP underwent spirometry and chest computed tomography (CT) at full inspiration and end-expiration. On inspiratory and expiratory chest CT images, CSA at the intrathoracic trachea was measured for all CT slices, and the mean and minimum tracheal CSA were obtained. Correlations between the tracheal CSA and spirometric values were assessed by Spearman's rank correlation analysis. Results: Tracheal CSA measurements for inspiratory and expiratory scans were significantly correlated with FEV1, FEV25-75%, and peak flow values (ρ = 0.51-0.86, p < 0.01). During each inspiratory or expiratory phase, the minimum tracheal CSA achieved a higher correlation coefficient with spirometric values than the mean CSA. Conclusion: Tracheal dimensions for both inspiratory and expiratory CT are significant predictors of pulmonary function in patients with RP. The narrowest tracheal dimension likely determines the severity of airflow limitation in RP.
Premature menopause in a multi-ethnic population study of the menopause transition.

BACKGROUND Premature menopause, also termed premature ovarian failure (POF), is characterized by cessation of menstruation before the age of 40 years. Little information is available on the general prevalence of POF or on the prevalence by ethnic group. There is also a lack of information on the association of POF with health indicators. METHODS A cross-sectional survey of women aged 40-55 years was conducted at seven sites in the USA to determine eligibility for a community-based, multi-ethnic longitudinal study of the peri-menopause (The Study of Women Across the Nation, SWAN). Interview data were used to (i). determine the prevalence of self-reported POF overall and by ethnic group, and (ii). assess the association of POF with selected self-reported variables related to health. Cases of POF included only women with no discernible cause for POF. RESULTS POF was reported by 1.1% (126/11 652) of women. By ethnicity, 1.0% (95% CI, 0.7-1.4) of Caucasian, 1.4% (95% CI, 1.0-2.1) of African American, 1.4% (95% CI, 0.8-2.5) of Hispanic, 0.5% (95% CI, 0.1-1.9) of Chinese and 0.1% (95% CI, 0.02-1.1) of Japanese women experienced POF. The differences in frequency across ethnic groups were statistically significant (P = 0.01). Only Caucasian, African American and Hispanic women were included in further analyses since too few Asian women had POF. In a multivariate model, POF was independently associated with osteoporosis, female hormone use (excluding oral contraceptives), higher body mass index (BMI) and current smoking after adjustment for education level, ability to pay for basics, site and age at interview. In Caucasian women, use of female hormones, osteoporosis, severe disability and smoking were significantly associated with POF. In contrast, POF in African American women was associated with higher BMI and female hormone use, but not osteoporosis. CONCLUSIONS The prevalence of POF appears to vary by ethnicity. Health factors associated with POF also vary by ethnicity but because of the cross-sectional study design, it is not possible to determine cause and effect relationships. Health risks of POF would benefit from further study.