Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoadiponectinemia as a Predictor for the Development of Hypertension: A 5-Year Prospective Study

Low circulating levels of adiponectin, an adipokine with insulin-sensitizing, antiatherogenic, and anti-inflammatory properties, are found in hypertensive patients. Adiponectin replenishment ameliorated hypertension in adiponectin-deficient mice or obese, hypertensive mice with hypoadiponectinemia, suggesting an etiologic role of adiponectin in hypertension. We aimed to determine, in this 5-year prospective study, whether hypoadiponectinemia could predict the development of hypertension in a nondiabetic Chinese cohort. A total of 577 subjects (249 men and 328 women) were recruited from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study and prospectively followed up for 5 years. The relationship of serum adiponectin with the development of hypertension (sitting blood pressure ≥140/90 mm Hg) was investigated in a nested case–control study consisting of 70 subjects who had developed hypertension on follow-up and 140 age- and sex-matched control subjects who were normotensive both at baseline and at year 5. At baseline, serum adiponectin level in the lowest sex-specific tertile was more likely to be associated with hypertension (P=0.003 versus the highest tertile, after adjusting for age, body mass index, fasting insulin, and high-sensitivity C-reactive protein). At year 5, baseline serum adiponectin was a significant independent predictor of incident hypertension in the nested case–control study (P=0.015; age adjusted), together with mean arterial pressure (P<0.001), high-sensitivity C-reactive protein (P=0.018), and body mass index (P=0.004). Normotensive subjects with baseline serum adiponectin levels in the lowest sex-specific tertile had an increased risk of becoming hypertensive (adjusted odds ratio: 2.76; 95% CIs: 1.06 to 7.16; P=0.037 versus highest tertile). Our data suggest that hypoadiponectinaemia may be involved in the pathogenesis of hypertension in humans.
Social Psychology and Software Teams: Establishing Task-Effective Group Norms

It's a common belief that groups that possess appropriate expertise and work well together will be more likely to successfully complete a project. However, social psychological research shows that getting the right mix of people doesn't guarantee a successful outcome. Group success also relies on group norms, which are derived as much from the group's context as from the people in it. A small, preliminary study illustrates how norm manipulation affected how well groups performed requirements elicitation. Results show that groups performed better on this task when norms emphasized creativity rather than agreeability. Norm manipulation might be a practical way to enhance group performance in software engineering tasks. There is an erratum in this article: in Figure 1, the description in the &#x201C;Constructive norm condition&#x201D; box should have read &#x201C;Priming: list what they had learned in their requirements-analysis course. &#x201D; The description in the &#x201C;Critical norm condition&#x201D; box should have read &#x201C;Priming: debate and reach consensus on the statement&#x2018;Requirements specifications should always reflect design constraints. &#x2019;&#x201D;
Cleavage of IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis

Degradation of immunoglobulins is an effective strategy of bacteria to evade the immune system. We have tested whether human IgG is a substrate for gingipain K of Porphyromonas gingivalis and found that the enzyme can hydrolyze subclass 1 and 3 of human IgG. The heavy chain of IgG1 was cleaved at a single site within the hinge region, generating Fab and Fc fragments. IgG3 was also cleaved within the heavy chain, but at several sites around the CH2 region. Investigation of the enzyme kinetics of IgG proteolysis by gingipain K, using FPLC‐ and isothermal titration calorimetry‐based assays followed by Hill plots, revealed non‐Michaelis‐Menten kinetics involving a mechanism of positive cooperativity. In ex vivo studies, it was shown that gingipain K retained its IgG hydrolyzing activity in human plasma despite the high content of natural protease inhibitors; that IgG1 cleavage products were detected in gingival crevicular fluid samples from patients with severe periodontitis; and that gingipain K treatment of serum samples from patients with high antibody titers against P. gingivalis significantly hindered opsonin‐dependent phagocytosis of clinical isolates of P. gingivalis by neutrophils. Altogether, these findings underline a biological function of gingipain K as an IgG protease of pathophysiological importance. —Vincents, B. , Guentsch, A. , Kostolowska, D. , von Pawel‐Rammingen, U. , Eick, S. , Potempa, J., Abrahamson, M. Cleavage of IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis. FASEB J. 25, 3741–3750 (2011). www.fasebj. org
Carotid Artery Wall Thickness and Risk of Stroke Subtypes: The Atherosclerosis Risk in Communities Study

Background and Purpose— Understanding associations of carotid atherosclerosis with stroke subtypes may contribute to more effective prevention of stroke. Methods— Between 1987 and 1989, 13 560 men and women aged 45 to 64 years and free of clinical stroke took part in the first examination of the Atherosclerosis Risk in Communities (ARIC) study. Incident strokes were ascertained by hospital surveillance. Results— During an average follow-up of 15.7 years, 82 incident hemorrhagic and 621 incident ischemic strokes (131 lacunar, 358 nonlacunar, and 132 cardioembolic strokes) occurred. The incidence rates of hemorrhagic and ischemic strokes were greater across higher carotid intima-media thickness levels. Although this positive association was observed for all stroke subtypes, the age-, gender-, and race-adjusted risk ratios were higher for cardioembolic and nonlacunar strokes than for hemorrhagic and lacunar strokes. Compared with participants in the lowest quintile (<0.61 mm), the adjusted risk ratios for those in the highest quintile (≥0.85 mm) of intima-media thickness were 2.55 (95% CI, 1.09–5.94) for hemorrhagic, 2.89 (95% CI, 1.50–5.54) for lacunar, 3.61 (95% CI, 2.33–5.99) for nonlacunar, and 6.12 (95% CI, 2.71–13.9) for cardioembolic stroke. The risk ratios were attenuated by additional adjustment for covariates but remained statistically significant for nonlacunar and cardioembolic strokes (P for trend <0.001, respectively). The association between carotid intima-media thickness and lacunar stroke was somewhat stronger in blacks than in whites (P for interaction=0.07). Conclusions— Carotid atherosclerosis was associated with increased risk of all stroke subtypes, but the association of carotid atherosclerosis with stroke may vary by subtypes.
Localizing spatially and temporally objects and actions in videos. (Localiser spatio-temporallement des objets et des actions dans des vidéos)

The rise of deep learning has facilitated remarkable progress in video understanding. This thesis addresses three important tasks of video understanding: video object detection, joint object and action detection, and spatio-temporal action localization. Object class detection is one of the most important challenges in computer vision. Object detectors are usually trained on bounding-boxes from still images. Recently, video has been used as an alternative source of data. Yet, training an object detector on one domain (either still images or videos) and testing on the other one results in a significant performance gap compared to training and testing on the same domain. In the first part of this thesis, we examine the reasons behind this performance gap. We define and evaluate several domain shift factors: spatial location accuracy, appearance diversity, image quality, aspect distribution, and object size and camera framing. We examine the impact of these factors by comparing the detection performance before and after cancelling them out. The results show that all five factors affect the performance of the detectors and their combined effect explains the performance gap. While most existing approaches for detection in videos focus on objects or human actions separately, in the second part of this thesis we aim at detecting non-human centric actions, i.e., objects performing actions, such as cat eating or dog jumping. We introduce an end-to-end multitask objective that jointly learns object-action relationships. We compare it with different training objectives, validate its effectiveness for detecting object-action pairs in videos, and show that both tasks of object and action detection benefit from this joint learning. In experiments on the A2D dataset, we obtain state-of-the-art results on segmentation of object-action pairs. In the third part, we are the first to propose an action tubelet detector that leverages the temporal continuity of videos instead of operating at the frame level, as state-of- the-art approaches do. The same way modern detectors rely on anchor boxes, our tubelet detector is based on anchor cuboids by taking as input a sequence of frames and outputing tubelets, i.e., sequences of bounding boxes with associated scores. Our tubelet detector outperforms all state of the art on the UCF-Sports, J-HMDB, and UCF-101 action localization datasets especially at high overlap thresholds. The improvement in detection performance is explained by both more accurate scores and more precise localization.
Circulating MicroRNAs as Easy-to-Measure Aging Biomarkers in Older Breast Cancer Patients: Correlation with Chronological Age but Not with Fitness/Frailty Status

Circulating microRNAs (miRNAs) hold great promise as easily accessible biomarkers for diverse (patho)physiological processes, including aging. We have compared miRNA expression profiles in cell-free blood from older versus young breast cancer patients, in order to identify “aging miRNAs” that can be used in the future to monitor the impact of chemotherapy on the patient’s biological age. First, we assessed 175 miRNAs that may possibly be present in serum/plasma in an exploratory screening in 10 young and 10 older patients. The top-15 ranking miRNAs showing differential expression between young and older subjects were further investigated in an independent cohort consisting of another 10 young and 20 older subjects. Plasma levels of miR-20a-3p, miR-30b-5p, miR106b, miR191 and miR-301a were confirmed to show significant age-related decreases (all p≤0.004). The remaining miRNAs included in the validation study (miR-21, miR-210, miR-320b, miR-378, miR-423-5p, let-7d, miR-140-5p, miR-200c, miR-374a, miR376a) all showed similar trends as observed in the exploratory screening but these differences did not reach statistical significance. Interestingly, the age-associated miRNAs did not show differential expression between fit/healthy and non-fit/frail subjects within the older breast cancer cohort of the validation study and thus merit further investigation as true aging markers that not merely reflect frailty.
Blocking the transcription factor E2F/DP by dominant-negative mutants in a normal breast epithelial cell line efficiently inhibits apoptosis and induces tumor growth in SCID mice

The transcription factor E2F is regulated during the cell cycle through interactions with the product of the retinoblastoma susceptibility gene and related proteins. It is thought that E2F-mediated gene regulation at the G1/S boundary and during S phase may be one of the rate-limiting steps in cell proliferation. It was reported that in vivo overexpression of E2F-1 in fibroblasts induces S phase entry and leads to apoptosis. This observation suggests that E2F plays a role in both cell cycle regulation and apoptosis. To further understand the role of E2F in cell cycle progression, cell death, and tumor development, we have blocked endogenous E2F activity in HBL-100 cells, derived from nonmalignant human breast epithelium, using dominant-negative mutants under the control of a tetracycline-dependent expression system. We have shown here that induction of dominant-negative mutants led to strong downregulation of transiently transfected E2F-dependent chloramphenicol acetyl transferase reporter constructs and of endogenous c-myc, which has been described as a target gene of the transcription factor E2F/DP. In addition, we have shown that blocking of E2F could efficiently protect from apoptosis induced by serum starvation within a period of 10 d, whereas control cells started to die after 24 h. Surprisingly, blocking of E2F did not alter the rate of proliferation or of DNA synthesis of these cells; this finding indicates that cell-cycle progression could be driven in an E2F- independent manner. In addition, we have been able to show that blocking of endogenous E2F in HBL-100 cells led to rapid induction of tumor growth in severe combined immunodeficiency mice. No tumor growth could be observed in mice that received mock-transfected clones or tetracycline to block expression of the E2F mutant constructs in vivo. Thus, it appears that E2F has a potential tumor-suppressive function under certain circumstances. Furthermore, we provide evidence that dysregulation of apoptosis may be an important step in tumorigenesis.
Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation.

CONTEXT Catechol O-methyltransferase (COMT), the major enzyme determining cortical dopamine flux, has a common functional polymorphism (val(158)met) that affects prefrontal function and working memory capacity and has also been associated with anxiety and emotional dysregulation. OBJECTIVES To examine COMT val(158)met effects on corticolimbic circuitry reactivity and functional connectivity during processing of biologically salient stimuli, as well as the relationship to the temperamental trait of novelty seeking. DESIGN Within-subject functional magnetic resonance imaging study. SETTING National Institute of Mental Health, Genes, Cognition, and Psychosis Program, Bethesda, Md. Patients One hundred one healthy subjects of both sexes. RESULTS We found that the met allele was associated with a dose-dependent increase in hippocampal formation and ventrolateral prefrontal cortex activation during viewing of faces displaying negative emotion. In met/met homozygotes, limbic and prefrontal regions showed increased functional coupling. Moreover, in these same subjects, the magnitude of amygdala-orbitofrontal coupling was inversely correlated with novelty seeking, an index of temperamental inflexibility. CONCLUSIONS Our results indicate that heritable variation in dopamine neurotransmission associated with the met allele of the COMT polymorphism results in heightened reactivity and connectivity in corticolimbic circuits. This may reflect a genetic predisposition for inflexible processing of affective stimuli, a mechanism possibly accounting for aspects of arousal and behavioral control that contribute to emotional dysregulation previously reported in met/met individuals.
The Role of HOXB9 and miR-196a in Head and Neck Squamous Cell Carcinoma

Background Previous studies have demonstrated that a number of HOX genes, a family of transcription factors with key roles in early development, are up-regulated in head and neck squamous cell carcinoma (HNSCC) and other cancers. The loci of several Homeobox (HOX) genes also contain microRNAs (miRs), including miR-196a. Methods Global miR expression and expression of all 39 HOX genes in normal oral keratinocytes (NOKs), oral pre-malignant (OPM) and HNSCC cells was assessed by expression microarray and qPCR and in tissues by immunohistochemistry (IHC) and qPCR of laser microdissected (LCM) tissues. Expression of miR196a and HOXB9 was reduced using anti-miR-196a and siRNA, respectively. Expression microarray profiles of anti-miR196a and pre-miR196a transfected cells were compared to parental cells in order to identify novel targets of miR-196a. Putative miR196a targets were validated by qPCR and were confirmed as binding to the 3’UTR of miR196a by a dual luciferase reporter assay combined with mutational analysis of the miR-196a binding site. Results miR-196a and HOXB9 are highly expressed in HNSCC compared to NOKs, a pattern also seen in HNSCC tissues by HOXB9 IHC and qPCR of miR-196a in LCM tissue. Knock-down of miR-196a expression decreased HNSCC cell migration, invasion and adhesion to fibronectin, but had no effect on proliferation. Furthermore, knock-down of HOXB9 expression decreased migration, invasion and proliferation but did not alter adhesion. We identified a novel primary mRNA transcript containing HOXB9 and miR196a-1 as predicted from in-silico analysis. Expression array analysis identified a number of miR196a targets, including MAMDC2 and HOXC8. We confirmed that MAMDC2 is a novel miR-196a target using a dual luciferase reporter assay with the effect abolished on mutation of the binding site. Conclusions These results show that miR-196a and HOXB9 are overexpressed, perhaps co-ordinately, as HNSCC develops and exert a pro-tumourigenic phenotype in HNSCC and OPM cells.
Long-Term Outcomes of Cultivated Limbal Epithelial Transplantation: Evaluation and Comparison of Results in Children and Adults

Purpose. To compare the long-term clinical outcomes of cultivated limbal epithelial transplantation (CLET) in children and adults with limbal stem cell deficiency. Design. Retrospective case series. Methods. Case records of patients with limbal stem cell deficiency (LSCD) who underwent CLET from April 2004 to December 2014 were studied. Outcome measures were compared in terms of anatomical success and visual improvement. Parameters for total anatomical success were avascular, epithelized, and clinically stable corneal surface without conjunctivalization, whereas partial anatomical success was considered when mild vascularization (sparing centre of cornea) and mild conjunctivalization were noted along with complete epithelization. Results. A total of 62 cases underwent the CLET procedure: 38 (61.3%) were children and 24 (38.7%) were adults. Patients with unilateral LSCD (33 children and 21 adults) had autografts and those with bilateral LSCD (5 children and 3 adults) had allografts. Amongst the 54 autografts partial and total anatomical success were noted in 21.2% and 66.6% children, respectively, and 19.0% and 80.9% in adults, respectively (p value 0.23). Visual improvement of 1 line and ≥2 lines was seen in 57.5% and 21.2% children, respectively, and 38% and 38% in adults, respectively (p value 0.31). Conclusion. Cultivated limbal epithelial transplantation gives good long-term results in patients with LSCD and the outcomes are comparable in children and adults.
Low-latency hard real-time communication over switched Ethernet

Ethernet, the most widely used commodity network, increasingly moves toward switches as implementation technology thus replacing buses. This allows to use traffic shaping techniques to implement hard real-time distributed systems on commodity networks. However, because Ethernet switches lack build-in policing features, nodes connected by switched Ethernet need to be cooperative. Although the theory behind traffic shaping for real-time communication is known for some time, it has not been considered for Ethernet so far. In this paper, we present the implementation of traffic shaping on switched Ethernet technology. We make thorough experiments to understand the cost and practical limits of using fast and gigabit Ethernet for hard real-time communication. We do measurements to analyze properties of switches and delays that we can achieve using these switches. We further analyze the influences of non real-time Linux nodes sharing the network.
Moderate Caveolin-1 Downregulation Prevents NADPH Oxidase–Dependent Endothelial Nitric Oxide Synthase Uncoupling by Angiotensin II in Endothelial Cells

Objective— We analyzed the role of caveolin-1 (Cav-1) in the cross-talk between NADPH oxidase and endothelial nitric oxide synthase (eNOS) signaling in endothelial caveolae. Methods and Results— In intact endothelial cells, angiotensin II (AII) concurrently increased NO and O2 −· production (to 158±12% and 209±5% of control). NO production was sensitive to inhibition of NADPH oxidase and small interfering RNA downregulation of nonreceptor tyrosine kinase cAbl. Reciprocally, N-nitro-L-arginine methyl ester, a NOS inhibitor, partly inhibited O2 −· stimulated by AII (by 47±11%), indicating eNOS uncoupling, as confirmed by increased eNOS monomer/dimer ratio (by 35%). In endothelial cell fractions separated by isopycnic ultracentrifugation, AII promoted colocalization of cAbl and the NADPH oxidase subunit p47phox with eNOS to Cav-1-enriched fractions, as confirmed by proximity ligation assay. Downregulation of Cav-1 by small interfering RNA (to 50%), although it preserved eNOS confinement, inhibited AII-stimulated p47phox translocation and NADPH oxidase activity in Cav-1-enriched fractions and reversed eNOS uncoupling. AII infusion produced hypertension and decreased blood hemoglobin-NO in Cav-1+/+ mice but not in heterozygote Cav-1+/− mice with similar Cav-1 reduction. Conclusion— Cav-1 critically regulates reactive oxygen species–dependent eNOS activation but also eNOS uncoupling in response to AII, underlining the possibility to treat endothelial dysfunction by modulating Cav-1 abundance.
Herpesvirus Saimiri Transforms Human T-Cell Clones to Stable Growth without Inducing Resistance to Apoptosis

ABSTRACT Herpesvirus saimiri (HVS) transforms human T cells to stable growth in vitro. Since HVS codes for two different antiapoptotic proteins, growth transformation by HVS might be expected to confer resistance to apoptosis. We found that the expression of both viral antiapoptotic genes was restricted to cultures with viral replication and absent in growth-transformed human T cells. A comparative examination of HVS-transformed T-cell clones and their native parental clones revealed that the expression of Bcl-2, Bcl-XL, Bax, and members of the tumor necrosis factor receptor (TNF-R) superfamily with a death domain, namely, TNF-RI, CD95, and TRAMP, were not modulated by HVS. Expression of CD30 was induced in HVS-transformed T cells, and these cells also expressed the CD30 ligand. Uninfected and transformed T cells were sensitive to CD95 ligation but resistant to apoptosis mediated by TRAIL or soluble TNF-α. CD95 ligand was constitutively expressed on transformed but not uninfected parental T cells. Both cell types showed similar sensitivity to cell death induction or inhibition of T-cell activation mediated by irradiation, oxygen radicals, dexamethasone, cyclosporine, and prostaglandin E2. Altogether, this study strongly suggests that growth transformation by HVS is based not on resistance to apoptosis but, rather, on utilization of normal cellular activation pathways.