Miracle-dz/UniFAR-FTUs huggingface dataset:
Complement reduction impairs the febrile response of guinea pigs to endotoxin.

Although it is generally believed that circulating exogenous pyrogens [e.g., lipopolysaccharides (LPS)] induce fever via the mediation of endogenous pyrogens (EP) such as cytokines, the first of these, tumor necrosis factor-α, is usually not detectable in blood until at least 30 min after intravenous administration of LPS, whereas the febrile rise begins within 15 min after its administration. Moreover, although abundant evidence indicates that circulating LPS is cleared primarily by liver macrophages [Kupffer cells (KC)], these do not secrete EP in immediate response. This would imply that other factors, presumably evoked earlier than EP, may mediate the onset of the febrile response to intravenous LPS. It is well known that blood-borne LPS very rapidly activates the intravascular complement (C) system, some components of which in turn stimulate the quick release into blood of various substances that have roles in the acute inflammatory reaction. KC contain receptors for C components and are in close contact with afferent vagal terminals in the liver; the involvement of hepatic vagal afferents in LPS-induced fever has recently been shown. In this study, we tested the hypothesis that the initiation of fever by intravenous LPS involves, sequentially, the C system and KC. To test this postulated mechanism, we measured directly the levels of prostaglandin E2(PGE2) in the interstitial fluid of the preoptic anterior hypothalamus (POA), the presumptive site of the fever-producing controller, of conscious guinea pigs over their entire febrile course, before and after C depletion by cobra venom factor (CVF) and before and after elimination of KC by gadolinium chloride (GdCl3). CVF and GdCl3 pretreatment each individually attenuated the first of the biphasic core temperature (Tc) rises after intravenous LPS, inverted the second into a Tcfall, and greatly reduced the usual fever-associated increase in POA PGE2. We conclude, therefore, that C activation may indeed be pivotal in the induction of fever by intravenous LPS and that substance(s) generated presumably by KC in almost immediate reaction to the presence of LPS and/or C may transmit pyrogenic signals via hepatic vagal afferents to the POA, where they rapidly induce the production of PGE2 and, hence, fever.
Dynamic–Mechanical Properties of Bioartificial Polymeric Materials

Bioartificial polymeric materials represent a new class of polymeric materials based on blends of synthetic and natural polymers, designed with the purpose of producing new materials with enhanced properties with respect to the single components. The mechanical properties of bioartificial materials prepared using poly(vinyl alcohol) (PVA), poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) as synthetic components, and collagen (SC), gelatin, starch, hyaluronic acid (HA) and dextran as biological components, were investigated by dynamic mechanical thermal analysis. The materials were prepared in the form of films or hydrogels and treated by glutaraldehyde (GTA) vapour or thermal dehydration in order to reduce their solubility in water. The results indicate that SC/PVA, gelatin/PVA and starch/PVA films behave as biphasic systems, showing good mechanical properties over a wide range of temperature. It was observed that the GTA procedure affects only the biological component of the SC/PVA and gelatin/PVA blends, whilst the thermal treatment influences mainly the synthetic polymer. In the case of HA/PVA hydrogels, a modulus variation was found with the HA content related to the organization degree and perfection of the PVA network structure. It seems evident that, in the experimental conditions used, dextran/PAA mixtures behave as miscible blends showing a glass transition intermediate between those of the pure components. With both untreated and GTA-treated gelatin/PMAA blends, it was not possible to evaluate the miscibility of the systems; it could only be affirmed that these materials show good mechanical properties over a wide range of temperature. © 1997 SCI.
Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin

Regulation of gene expression is achieved by sequence-specific transcriptional regulators, which convey the information that is contained in the sequence of DNA into RNA polymerase activity. This is achieved by the recruitment of transcriptional co-factors. One of the consequences of co-factor recruitment is the control of specific properties of nucleosomes, the basic units of chromatin, and their protein components, the core histones. The main principles are to regulate the position and the characteristics of nucleosomes. The latter includes modulating the composition of core histones and their variants that are integrated into nucleosomes, and the post-translational modification of these histones referred to as histone marks. One of these marks is the methylation of lysine 4 of the core histone H3 (H3K4). While mono-methylation of H3K4 (H3K4me1) is located preferentially at active enhancers, tri-methylation (H3K4me3) is a mark found at open and potentially active promoters. Thus, H3K4 methylation is typically associated with gene transcription. The class 2 lysine methyltransferases (KMTs) are the main enzymes that methylate H3K4. KMT2 enzymes function in complexes that contain a necessary core complex composed of WDR5, RBBP5, ASH2L, and DPY30, the so-called WRAD complex. Here we discuss recent findings that try to elucidate the important question of how KMT2 complexes are recruited to specific sites on chromatin. This is embedded into short overviews of the biological functions of KMT2 complexes and the consequences of H3K4 methylation.
Arrowhead detection in biomedical images

Medical images in biomedical documents tend to be complex by nature and often contain several regions that are annotated using arrows. Arrowhead detection is a critical precursor to regionof-interest (ROI) labeling and image content analysis. To detect arrowheads, images are first binarized using fuzzy binarization technique to segment a set of candidates based on connected component principle. To select arrow candidates, we use convexity defect-based filtering, which is followed by template matching via dynamic programming. The similarity score via dynamic time warping (DTW) confirms the presence of arrows in the image. Our test on biomedical images from imageCLEF 2010 collection shows the interest of the technique.
Optimized Fairness Cell Selection for 3GPP LTE-A Macro-Pico HetNets

Pico cell has been brought to cellular networks as a new technology to deliver cost-effective coverage and capacity to hard-to-reach places, and also increase capacity by cell splitting in hotspots with very dense phone usage. However, according to existing strongest receiving signal association method, pico cells with the extremely low transmitting power are significantly limited in the presence of macro coverage. Thus, the new introduced pico frequency resource will not be fully exploited in this unbalanced user distributions among macro and pico cells. In this paper, by jointly considering the long term channel condition and load balance in this macro-pico coexisted heterogeneous network, we formulate the cell selection problem into a network-wide proportional fairness optimization. Both optimal solution (by dynamic programming) and cost efficient algorithm (greedy heuristics) are proposed. In 3GPP LTE-A heterogeneous network scenario, the system-level performance evaluation shows that, compared with the conventional strongest signal cell selection scheme, the proposed optimized fairness cell selection methods could achieve significant performance gains especially for the cell edge users.
Aberrant Development of Speech Processing in Young Children with Autism: New Insights from Neuroimaging Biomarkers

From the time of birth, a newborn is continuously exposed and naturally attracted to human voices, and as he grows, he becomes increasingly responsive to these speech stimuli, which are strong drivers for his language development and knowledge acquisition about the world. In contrast, young children with autism spectrum disorder (ASD) are often insensitive to human voices, failing to orient and respond to them. Failure to attend to speech in turn results in altered development of language and social-communication skills. Here, we review the critical role of orienting to speech in ASD, as well as the neural substrates of human voice processing. Recent functional neuroimaging and electroencephalography studies demonstrate that aberrant voice processing could be a promising marker to identify ASD very early on. With the advent of refined brain imaging methods, coupled with the possibility of screening infants and toddlers, predictive brain function biomarkers are actively being examined and are starting to emerge. Their timely identification might not only help to differentiate between phenotypes, but also guide the clinicians in setting up appropriate therapies, and better predicting or quantifying long-term outcome.
Risk and protective factors for heavy binge alcohol use among American Indian adolescents utilizing emergency health services

ABSTRACT Background: American Indian (AI) adolescents are disproportionately burdened by alcohol abuse and heavy binge use, often leading to problematic drinking in adulthood. However, many AI communities also have large proportions of adults who abstain from alcohol. Objective: To understand these concurrent and divergent patterns, we explored the relationship between risk and protective factors for heavy binge alcohol use among a reservation-based sample of AI adolescents. Methods: Factors at individual, peer, family, and cultural/community levels were examined using a cross-sectional case–control study design. Cases were adolescents with recent heavy binge alcohol use that resulted in necessary medical care. Controls had no lifetime history of heavy binge alcohol use. 68 cases and 55 controls were recruited from emergency health services visits. Participants were 50% male; average age 15.4 years old, range 10 to 19. Independent variables were explored using logistic regression; those statistically significant were combined into a larger multivariate model. Results: Exploratory analyses showed adolescents who were aggressive, impulsive, had deviant peers, poor family functioning or more people living at home were at greater risk for heavy binge alcohol use. Protective factors included attending school, family closeness, residential stability, social problem-solving skills, having traditional AI values and practices, and strong ethnic identity. Confirmatory analysis concluded that school attendance and residential stability reduce the probability of heavy binge alcohol use, even among those already at low risk. Conclusions: Findings deepen the understanding of AI adolescent heavy binge alcohol use and inform adolescent intervention development fostering trajectories to low-risk drinking and abstinence.
On cyberattack mechanisms

Cybercrimes and cyberattacks have become serious threats to the internet-based life and work of people and organisations. Cyberdefenders and law enforcement have been waging a losing war against the determined and clever cybercriminals and cyberwarriors. The primary elements of cyberattack include hacking, malware, and DDoS attacks. This paper provides technical descriptions of how each element of cyberattack works, and what are some of the software tools used to aid it.
Evaluation of a countrywide implementation of the world health organisation surgical safety checklist in Madagascar

Background The 2009 World Health Organisation (WHO) surgical safety checklist significantly reduces surgical mortality and morbidity (up to 47%). Yet in 2016, only 25% of East African anesthetists regularly use the checklist. Nationwide implementation of the checklist is reported in high-income countries, but in low- and middle-income countries (LMICs) reports of successful implementations are sparse, limited to single institutions and require intensive support. Since checklist use leads to the biggest improvements in outcomes in LMICs, methods of wide-scale implementation are needed. We hypothesized that, using a three-day course, successful wide-scale implementation of the checklist could be achieved, as measured by at least 50% compliance with six basic safety processes at three to four months. We also aimed to determine predictors for checklist utilization. Materials and methods Using a blended educational implementation strategy based on prior pilot studies we designed a three-day dynamic educational course to facilitate widespread implementation of the WHO checklist. The course utilized lectures, film, small group breakouts, participant feedback and simulation to teach the knowledge, skills and behavior changes needed to implement the checklist. In collaboration with the Ministry of Health and local hospital leadership, the course was delivered to 427 multi-disciplinary staff at 21 hospitals located in 19 of 22 regions of Madagascar between September 2015 and March 2016. We evaluated implementation at three to four months using questionnaires (with a 5-point Likert scale) and focus groups. Multivariate linear regression was used to test predictors of checklist utilization. Results At three to four months, 65% of respondents reported always using the checklist, with another 13% using it in part. Participant’s years in practice, hospital size, or surgical volume did not predict checklist use. Checklist use was associated with counting instruments (p< 0.05), but not with verifying: patient identity, difficult intubation risk, risk of blood loss, prophylactic antibiotic administration, or counting needles and sponges. Conclusion Use of a multi-disciplinary three-day course for checklist implementation resulted in 78% of participants using the checklist, at three months; and an increase in counting surgical instruments. Successful checklist implementation was not predicted by participant length of medical service, hospital size or surgical volume. If reproducible in other countries, widespread implementation in LMICs becomes a realistic possibility.
Effect of PGE1, PGI2, and PGF2α analogs on collagen gel compaction in vitro and interstitial pressure in vivo.

Acute inflammation in skin is accompanied by increased negativity of interstitial fluid pressure (PIF), which will increase capillary fluid filtration and thereby potentiate edema formation. A series of studies indicates that the connective tissue cells in rat dermis are involved in the control of PIF and mediate this response. The present study describes a novel effect of prostaglandin (PG) E1 isopropyl ester, carbaprostacyclin (PGI2 analog), and latanoprost (PGF2α analog) on edema formation and PIF in parallel with their action on the fibroblast-populated collagen gel contraction assay. The prostaglandins were injected subdermally in pentobarbital-anesthetized rats. PIF was measured with a servo-controlled counterpressure system after circulatory arrest had been induced with saturated potassium chloride. Circulatory arrest was induced to limit edema formation that would raise interstitial fluid volume and thereby attenuate a possible increased negativity of PIF. PGE1 (0.91 mM) and carbaprostacyclin (1.28 mM) lowered PIF from a control value of -0.8 ± 0.4 mmHg to -3.0 ± 0.4 ( P < 0.01) and -3.7 ± 0.9 ( P < 0.01) mmHg, respectively, within 45 min in a dose-dependent manner. Edema formation was measured in separate experiments. PGE1 and carbaprostacyclin significantly increased interstitial fluid volume (extravascular51Cr-EDTA space) at concentrations as low as 0.1 and 1.1 μM, respectively. Latanoprost had no effect on PIF or edema formation. However, latanoprost reversed, in a dose-dependent manner, an increased negativity of PIF accompanying the anaphylactic reaction to dextran. In the gel contraction assay with human diploid fibroblasts (AG 1518), a corresponding specificity was observed where PGE1 and carbaprostacyclin effectively inhibited gel contraction although latanoprost had no effect. Thus the present data demonstrate a novel effect of prostaglandins and provide further evidence for active modulation of PIF via loose connective tissue cells.
Externalizing Behaviour for Analysing System Models

Systems models have recently been introduced to model organisationsandevaluate their vulnerability to threats and especially insiderthreats. Especially for the latter these models are very suitable, since insiders can be assumed to have more knowledge about the attacked organisation than outside attackers. Therefore, manyattacks are considerably easier to be performed for insiders than for outsiders. However, current models do not support explicit specification of different behaviours. Instead, behaviour is deeply embedded in the analyses supported by the models, meaning that it is a complex, if not impossible task to change behaviours. Especially when considering social engineering or the human factor in general, the ability to use different kinds of behaviours is essential. In this work we present an approach to make the behaviour a separate component in system models, and explore how to integrate in existing models.
Tyrosine phosphorylation and association of p130Cas and c-Crk II by ANG II in vascular smooth muscle cells.

In cultured vascular smooth muscle cells (VSMC), angiotensin II (ANG II) stimulated tyrosine phosphorylation of multiple proteins including a 130-kDa protein. This 130-kDa protein was identified as a Crk-associated substrate, p130Cas. ANG II-stimulated tyrosine phosphorylation of p130Cas was rapid, concentration dependent, and inhibited by the AT1-receptor antagonist CV-11974. Neither downregulation of protein kinase C by long exposure of cells to phorbol 12,13-dibutyrate nor blockade of Ca2+ mobilization by 1,2-bis(2-aminophenoxy)ethane- N, N, N', N'-tetraacetic acid acetoxymethyl ester had an effect on ANG II-stimulated tyrosine phosphorylation of p130Cas. Stimulation with ANG II enhanced the specific association of p130Cas with c-Crk II. The time course of the association of p130Cas and c-Crk II was similar to that of tyrosine phosphorylation of p130Cas. c-Crk II was also tyrosine phosphorylated in response to ANG II. These results indicate that ANG II induces tyrosine phosphorylation of p130Cas and c-Crk II and their specific association, suggesting a potential role of the p130Cas-c-Crk II complex in ANG II signal transduction in VSMC.
Dissociation between regional dysfunction and β-adrenergic receptor signaling in heart failure.

We have previously shown that left ventricular (LV) pacing-induced heart failure is associated with preserved wall thickening in the interventricular septum (IVS) compared with the posterolateral wall (PLW). The current study focuses on the relationship between regional myocardial function and altered β-adrenergic receptor (β-AR) signaling. We studied 15 pigs: 6 controls and 9 paced from the left ventricle (225 beats/min, 26 ± 3 days). Heart failure was documented by decreased LV fractional shortening ( P < 0.0001) and increased left atrial pressure ( P < 0.0001). In heart failure, despite marked differences in basal regional function (percent wall thickening: IVS, 33 ± 10% vs. PLW, 13 ± 7%; P = 0.0003), there were no differences between the two regions in β-AR responsiveness, measured by regional wall thickening in response to dobutamine infusion and any measurement of adrenergic signaling. Adenylyl cyclase activity, β-AR number, and β-AR/Gscoupling were markedly reduced in failing LV without regional differences. In animals with heart failure, LV G protein receptor kinase (GRK) isoform 2 content was unchanged and GRK5, the other major GRK isoform, was increased more than threefold (IVS, 0.51 ± 0.20 vs. 0.12 ± 0.12 arbitrary densitometric units, P = 0.01; PLW, 0.47 ± 0.15 vs. 0.13 ± 0.09 arbitrary densitometric units, P = 0.03), but again, there were no regional differences. These data indicate that systemic rather than regional factors govern LV adrenergic signaling and that regional adrenergic signaling abnormalities poorly predict wall thickening in the same regions.
Role of nitric oxide in intrarenal hemodynamics in experimental diabetes mellitus in rats.

The role of nitric oxide (NO) in the regulation of the intrarenal microcirculation in streptozotocin (STZ)-induced diabetes mellitus in rats is not clear. We examined renal cortical and papillary hemodynamics in STZ rats and determined the effects of systemic inhibition and stimulation of NO synthesis. Renal blood flow in cortical (QCC), and inner medullary ascending (QAV) and descending (QDV) vasa recta capillaries was measured by fluorescence videomicroscopy in STZ Munich-Wistar rats and nondiabetic control rats. Ten days after STZ injection (80 mg/kg ip), basal QCC and QDV were significantly greater in STZ rats ( n = 16) compared with control rats ( n = 15). Infusion of N G-monomethyl-l-arginine (l-NMMA, 15 mg/kg bolus, 500 μg ⋅ min-1 ⋅ kg-1iv) decreased QCC (-41%), QAV (-38%), and QDV (-37%) in control rats ( n = 6) and to a significantly greater magnitude than in STZ rats ( n = 7), QCC (-14%), QAV (-20%), and QDV (-25%). Coinfusion ofl-arginine (l-Arg, 1 mg ⋅ kg-1 ⋅ min-1iv) with l-NMMA increased QCC to a significantly greater extent ( P < 0.01) in control rats compared with STZ rats. In subsequent studies, infusion ofl-Arg alone increased QCC (+50%), QAV (+16%), and QDV (+11%) in control rats ( n = 5) but had no effect in STZ rats ( n = 5). These results show that the response of renal cortical and papillary capillary blood flow to both inhibition and stimulation of NO synthesis is attenuated in the early onset of STZ-diabetes mellitus rats compared with control rats.
Increased expression of glomerular AT1 receptors in rats with myocardial infarction.

Rats with congestive heart failure demonstrate striking intrarenal vasoconstriction that contributes to reduced renal excretory function. We previously demonstrated that inhibition of angiotensin action reverses intrarenal vasoconstriction in rats 4-6 wk after coronary artery ligation. In the present study we tested the hypothesis that abnormalities in the expression and regulation of glomerular angiotensin receptors contribute to the intrarenal vasoconstriction. Because glomerular angiotensin type 1 (AT1) receptors normally downregulate in response to high local ANG II concentrations, we anticipated that glomerular AT1-receptor expression would be reduced in rats after myocardial infarction (MI). To our surprise, the density of glomerular AT1receptors was nearly double (97% increase, P < 0.002) that of controls, indicating an acquired abnormality in angiotensin receptor regulation. This was specific for renal glomeruli, because the density of angiotensin receptors on renal vasculature was decreased in rats after MI compared with normal controls. Glomerular AT1-receptor expression was downregulated by an acute pharmacological infusion of ANG II and upregulated by acute angiotensin-converting enzyme inhibition to a similar extent in MI and control rats. Renal cortical mRNA expression showed an increase in the renin mRNA-to-actin ratio and angiotensinogen-to-actin ratio, indicating stimulation of the intrarenal angiotensin system in rats after MI. The data indicate a specific dysregulation of AT1receptors in glomeruli but not blood vessels after MI.