Miracle-dz/UniFAR-FTUs huggingface dataset:
Citrullination-acetylation interplay guides E2F-1 activity during the inflammatory response

PAD4-mediated citrullination of E2F-1 transcription factor and its interplay with acetylation affects inflammatory gene expression. Peptidyl arginine deiminase 4 (PAD4) is a nuclear enzyme that converts arginine residues to citrulline. Although increasingly implicated in inflammatory disease and cancer, the mechanism of action of PAD4 and its functionally relevant pathways remains unclear. E2F transcription factors are a family of master regulators that coordinate gene expression during cellular proliferation and diverse cell fates. We show that E2F-1 is citrullinated by PAD4 in inflammatory cells. Citrullination of E2F-1 assists its chromatin association, specifically to cytokine genes in granulocyte cells. Mechanistically, citrullination augments binding of the BET (bromodomain and extra-terminal domain) family bromodomain reader BRD4 (bromodomain-containing protein 4) to an acetylated domain in E2F-1, and PAD4 and BRD4 coexist with E2F-1 on cytokine gene promoters. Accordingly, the combined inhibition of PAD4 and BRD4 disrupts the chromatin-bound complex and suppresses cytokine gene expression. In the murine collagen-induced arthritis model, chromatin-bound E2F-1 in inflammatory cells and consequent cytokine expression are diminished upon small-molecule inhibition of PAD4 and BRD4, and the combined treatment is clinically efficacious in preventing disease progression. Our results shed light on a new transcription-based mechanism that mediates the inflammatory effect of PAD4 and establish the interplay between citrullination and acetylation in the control of E2F-1 as a regulatory interface for driving inflammatory gene expression.
NITRIC OXIDE (NO), CITRULLINE - NO CYCLE ENZYMES, GLUTAMINE SYNTHETASE AND OXIDATIVE STRESS IN ANOXIA (HYPOBARIC HYPOXIA) AND REPERFUSION IN RAT BRAIN

Nitric oxide is postulated to be involved in the pathophysiology of neurological disorders due to hypoxia/ anoxia in brain due to increased release of glutamate and activation of N-methyl-D-aspartate receptors. Reactive oxygen species have been implicated in pathophysiology of many neurological disorders and in brain function. To understand their role in anoxia (hypobaric hypoxia) and reperfusion (reoxygenation), the nitric oxide synthase, argininosuccinate synthetase, argininosuccinate lyase, glutamine synthetase and arginase activities along with the concentration of nitrate /nitrite, thiobarbituric acid reactive substances and total antioxidant status were estimated in cerebral cortex, cerebellum and brain stem of rats subjected to anoxia and reperfusion. The results of this study clearly demonstrated the increased production of nitric oxide by increased activity of nitric oxide synthase. The increased activities of argininosuccinate synthetase and argininosuccinate lyase suggest the increased and effective recycling of citrulline to arginine in anoxia, making nitric oxide production more effective and contributing to its toxic effects. The decreased activity of glutamine synthetase may favor the prolonged availability of glutamic acid causing excitotoxicity leading to neuronal damage in anoxia. The increased formation of thiobarbituric acid reactive substances and decreased total antioxidant status indicate the presence of oxidative stress in anoxia and reperfusion. The increased arginase and sustained decrease of GS activity in reperfusion group likely to be protective.
Phylogeny and expression of canonical transient receptor potential (TRPC) genes in developing zebrafish

Background: Canonical transient receptor potential (TRPC) channels are nonselective, calcium‐permeable cation channels that are expressed in a great variety of organisms, tissues, and cell types. TRPC channels are known to be involved in the transduction of polymodal sensory input. Additionally, they are implicated in a variety of developmental processes. Distinct gating mechanisms have been elucidated so far, but their exact functional role in vertebrate organisms still needs to be resolved. Results: We now used the teleost Danio rerio to perform a comprehensive expression analysis of the trpc gene subfamily. Based on the sequence homology to the seven described mammalian TRPC channels, we identified 12 trpc genes in the zebrafish genome. All but trpc1 and trpc3 are represented by two paralogs. We further describe the specific expression patterns of trpc transcripts in whole‐mounts during the first 5 days of development. Conclusions: Consistent with their proposed role in sensory transduction zebrafish trpcs are predominantly expressed in neural structures such as the olfactory, visual, mechanosensitive, and motor systems. Intriguingly, zebrafish paralogs show mainly nonoverlapping expression patterns, suggesting that duplicated genes have either split their functions or have adapted new ones. Developmental Dynamics 242:1427–1441, 2013. © 2013 Wiley Periodicals, Inc.
D ec 2 00 1 Morphological Model for Colloidal Suspensions

The phase behavior of colloidal particles embedded in a binary fluid is influenced by wetting layers surrounding each particle. The free energy of the fluid film depends on its morphology, i.e., on size, shape and connectivity. Under rather natural assumptions a general expression for the Hamiltonian can be given extending the model of hard spheres to partially penetrable shapes including energy contributions related to the volume, surface area, mean curvature , and Euler characteristic of the wetting layer. The complex spatial structure leads to multi-particle interactions of the colloidal particles. The dependence of the morphology of the wetting layer on temperature and density can be studied using Monte-Carlo simulations and perturbation theory. A fluid-fluid phase separation induced by the wetting layer is observed which is suppressed when only two-particle interactions are taken into account instead of the inherent many-particle interaction of the wetting layer.
Circulating Tumor Cell Detection Predicts Early Metastatic Relapse After Neoadjuvant Chemotherapy in Large Operable and Locally Advanced Breast Cancer in a Phase II Randomized Trial

Purpose: Circulating tumor cells in blood from metastatic breast cancer patients have been reported as a surrogate marker for tumor response and shorter survival. The aim of this study was to determine whether circulating tumor cells are present in the blood of patients with large operable or locally advanced breast cancer before neoadjuvant chemotherapy and after neoadjuvant chemotherapy before surgery. Experimental Design: Blood samples of 7.5 mL were obtained on CellSave tubes from patients included in a phase II trial (REMAGUS 02). Circulating tumor cells were immunomagnetically separated and fluorescently stained by the CellSearch system. Blood from 20 metastatic breast cancer patients was used as a positive control. Results: From October 2004 to July 2006, preneoadjuvant chemotherapy and/or postneoadjuvant chemotherapy blood samples were obtained from 118 patients. At least 1 circulating tumor cell was detected in 22 of 97 patients with preneoadjuvant chemotherapy samples (23%; 95% confidence interval, 15-31%; median, 2 cells; range, 1-17 cells). Circulating tumor cell positivity rates were 17% in 86 postneoadjuvant chemotherapy samples and 27% in all 118 patients. Persistence of circulating tumor cells at the end of neoadjuvant chemotherapy was not correlated with treatment response. After a short median follow-up of 18 months, the presence of circulating tumor cells (P = 0.017), hormone receptor negativity, and large tumor size were independent prognostic factors for shorter distant metastasis–free survival. Conclusion: Circulating tumor cells can be detected by the CellSearch system at a low cutoff of 1 cell in 27% of patients receiving neoadjuvant chemotherapy. Circulating tumor cell detection was not correlated to the primary tumor response but is an independent prognostic factor for early relapse.
Phylogenetic relationships among four new complete mitogenome sequences of Pelophylax (Amphibia: Anura) from the Balkans and Cyprus

Abstract We present the full-length mitogenome sequences of four European water frog species: Pelophylax cypriensis, P. epeiroticus, P. kurtmuelleri and P. shqipericus. The mtDNA size varied from 17,363 to 17,895 bp, and its organization with the LPTF tRNA gene cluster preceding the 12 S rRNA gene displayed the typical Neobatrachian arrangement. Maximum likelihood and Bayesian inference revealed a well-resolved mtDNA phylogeny of seven European Pelophylax species. The uncorrected p-distance for among Pelophylax mitogenomes was 9.6 (range 0.01–0.13). Most divergent was the P. shqipericus mitogenome, clustering with the “P. lessonae” group, in contrast to the other three new Pelophylax mitogenomes related to the “P. bedriagae/ridibundus” lineage. The new mitogenomes resolve ambiguities of the phylogenetic placement of P. cretensis and P. epeiroticus.
Oligonucleotide Microarray for the Study of Functional Gene Diversity in the Nitrogen Cycle in the Environment

ABSTRACT The analysis of functional diversity and its dynamics in the environment is essential for understanding the microbial ecology and biogeochemistry of aquatic systems. Here we describe the development and optimization of a DNA microarray method for the detection and quantification of functional genes in the environment and report on their preliminary application to the study of the denitrification gene nirS in the Choptank River-Chesapeake Bay system. Intergenic and intragenic resolution constraints were determined by an oligonucleotide (70-mer) microarray approach. Complete signal separation was achieved when comparing unrelated genes within the nitrogen cycle (amoA, nifH, nirK, and nirS) and detecting different variants of the same gene, nirK, corresponding to organisms with two different physiological modes, ammonia oxidizers and denitrifying halobenzoate degraders. The limits of intragenic resolution were investigated with a microarray containing 64 nirS sequences comprising 14 cultured organisms and 50 clones obtained from the Choptank River in Maryland. The nirS oligonucleotides covered a range of sequence identities from approximately 40 to 100%. The threshold values for specificity were determined to be 87% sequence identity and a target-to-probe perfect match-to-mismatch binding free-energy ratio of 0.56. The lower detection limit was 10 pg of DNA (equivalent to approximately 107 copies) per target per microarray. Hybridization patterns on the microarray differed between sediment samples from two stations in the Choptank River, implying important differences in the composition of the denitirifer community along an environmental gradient of salinity, inorganic nitrogen, and dissolved organic carbon. This work establishes a useful set of design constraints (independent of the target gene) for the implementation of functional gene microarrays for environmental applications.
Cardiovascular risk factor management of myocardial infarction patients with and without diabetes in the Netherlands between 2002 and 2006: a cross-sectional analysis of baseline data

Objective We examined levels and trends in cardiovascular risk factors and drug treatment in myocardial infarction (MI) patients with and without diabetes. Design Cross-sectional analysis of baseline Alpha Omega Trial data, a randomised controlled trial. Setting 32 hospitals in the Netherlands. Participants In total, we had 1014 MI patients with diabetes (74% men) and 3823 without diabetes (79% men) aged 60–80 years, analysed over the period 2002–2006. Results Between 2002 and 2006, a significantly decreasing trend in the prevalence of obesity (−5%, ptrend=0.02) and in systolic blood pressure (BP) levels (−5 mm Hg, ptrend<0.0001) was demonstrated in non-diabetic patients, but not in diabetic patients. In 2006, obesity, mean systolic BP and serum triglyceride levels were significantly higher, whereas high-density lipoprotein cholesterol levels were lower in diabetic patients compared to those without. Prescription of antihypertensive drug (diabetic vs non-diabetic patients respectively, 95% vs 93%, p=0.08) and statin treatment were high (86% and 90%, p=0.11). Conclusions A high proportion of MI patients with and without diabetes was similarly treated with cardiovascular drugs. In spite of high drug treatment levels, more adverse risk factors were found in patients with diabetes.
A Data Capsule Framework For Web Services: Providing Flexible Data Access Control To Users

This paper introduces the notion of a secure data capsule, which refers to an encapsulation of sensitive user information (such as a credit card number) along with code that implements an interface suitable for the use of such information (such as charging for purchases) by a service (such as an online merchant). In our capsule framework, users provide their data in the form of such capsules to web services rather than raw data. Capsules can be deployed in a variety of ways, either on a trusted third party or the user's own computer or at the service itself, through the use of a variety of hardware or software modules, such as a virtual machine monitor or trusted platform module: the only requirement is that the deployment mechanism must ensure that the user's data is only accessed via the interface sanctioned by the user. The framework further allows an user to specify policies regarding which services or machines may host her capsule, what parties are allowed to access the interface, and with what parameters. The combination of interface restrictions and policy control lets us bound the impact of an attacker who compromises the service to gain access to the user's capsule or a malicious insider at the service itself.
Vascular Access for Hemodialysis - How to Maintain in Clinical Practice

Chronic access to the circulation became a reality in 1960 when Scribner, Dillard, and Quinton introduced the Teflon-Silastic arteriovenous (AV) shunt. The Scribner shunt rarely could be used for more than 3 months because of: interference of the external appliance with normal activity, infection, thrombosis, and bleeding [3]. These disadvantages were overcome by introduction of the subcutaneous AV fistula by Brescia, Cimino, Appel and Hurwich in 1966 which is a fistula between the artery above the wrist and the largest available vein in close proximity [4]. Their innovative approach remains the initial procedure of choice in patients who are candidates for long term hemodialysis.
Adaptive Virtual Machine Provisioning in Elastic Multi-tier Cloud Platforms

Virtual machines are allocated on demand in virtualized cloud platforms to provide flexible and reliable services. The major difficulty lies in satisfying the conflicting objectives of reducing response time while lowering resource costs. In this paper, a mathematical multi-tier framework for virtual machine allocation is proposed, which can be used to capture the performance of the cloud platform. We first use simulations to derive virtual resource allocation policies, and later use real benchmarking applications to verify the effectiveness of this framework. Experimental results show that the model can be simply and effectively used to satisfy the response time requirement as well as lowering the cost of using the virtual machine resources.
Thermal stresses in load-bearing glass-timber components

Thermal stresses can arise in glass used in architectonic realisations in buildings as a result of solar irradiation: that is, sunlight. The magnitude of these thermal stresses depends on the temperature conditions in the glass in terms of the temperature differences between warm and cold areas. The work described here has verified the existence and distribution of thermal stresses in glass, both theoretically and experimentally, in a load-bearing element made of glass and wood, when exposed to incident solar radiation and various degrees of shading. The finite element method was used in order to simulate the temperature distribution in the glass, together with the resulting associated thermal stresses. Parts of these model results were then compared with results and data from experimental investigations in a solar simulator. The experimental trials were carried out on a plain glass sheet and on a wood-framed glass sheet. This frame assembly saw the glass fitted in a wooden frame such that its edge was flush with the edges of the frame and therefore freely exposed to the surroundings. Two different grades of glass were analysed in the theoretical modelling and used in the experimental solar exposure: a clear glass, with a low absorption coefficient, and a tinted glass having a relatively high absorption coefficient. The experimental part of the work included two different finishes to the glass edge: as-cut, with no further attention, and cut and smoothed. The results from the finite element method calculations agree relatively well with the experimental results. When simulating the temperature values and distributions, the value of the coefficient of heat transfer is an important factor in determining the results. The coefficient can be given either a constant value, taken from a standard, or a calculated value that varies depending on the surface temperature and ambient temperature at every instant. For the clear glass with a low coefficient of absorption, the calculated temperatures did not differ significantly depending on which method had been used to provide a value for the coefficient of heat transfer. However, for the glass with a high coefficient of absorption, and when exposed to high solar intensity, a calculated value of coefficient of heat transfer should be used in order to arrive at relevant values of surface temperatures and stresses. Thermal tensile stresses have more effect on the total stress level than have stresses arising from typical in-service vertical loads.
An extensible speaker identification sidekit in Python

SIDEKIT is a new open-source Python toolkit that includes a large panel of state-of-the-art components and allow a rapid prototyping of an end-to-end speaker recognition system. For each step from front-end feature extraction, normalization, speech activity detection, modelling, scoring and visualization, SIDEKIT offers a wide range of standard algorithms and flexible interfaces. The use of a single efficient programming and scripting language (Python in this case), and the limited dependencies, facilitate the deployment for industrial applications and extension to include new algorithms as part of the whole tool-chain provided by SIDEKIT. Performance of SIDEKIT is demonstrated on two standard evaluation tasks, namely the RSR2015 and NIST-SRE 2010.
Stereo-based simultaneous localization, mapping and moving object tracking

Vision based simultaneous localization and mapping (SLAM) has recently received much research interest. However, vision based SLAM could be corrupted with the inclusion of moving entities, which makes it hard to operate in dynamic environments. Simultaneous localization, mapping and moving object tracking (SLAMMOT) serves as a solution to deal with moving objects while performing SLAM. The existing work has shown the feasibility of monocular SLAMMOT in dynamic environments. However, monocular SLAMMOT inherits the observability issue of bearings-only tracking in which moving entities would be unobservable according to motions of the camera and moving objects. In this paper, stereo-based SLAMMOT is proposed to solve the observability issue as well as increase the accuracy of localization, mapping and tracking. Simulation and experimental results demonstrate that the proposed stereo SLAMMOT is superior than monocular SLAMMOT in dynamic environments.
Comparing Different Early Warning Systems: Results from a Horse Race Competition Among Members of the Macro-Prudential Research Network

Over the recent decades researchers in academia and central banks have developed early warning systems (EWS) designed to warn policy makers of potential future economic and financial crises. These EWS are based on diverse approaches and empirical models. In this paper we compare the performance of nine distinct models for predicting banking crises resulting from the work of the Macroprudential Research Network (MaRs) initiated by the European System of Central Banks. In order to ensure comparability, all models use the same database of crises created by MaRs and comparable sets of potential early warning indicators. We evaluate the models’ relative usefulness by comparing the ratios of false alarms and missed crises and discuss implications for pratical use and future research. We find that multivariate models, in their many appearances, have great potential added value over simple signalling models. One of the main policy recommendations coming from this exercise is that policy makers can benefit from taking a broad methodological approach when they develop models to set macro-prudential instruments.
What Makes an Information System More Preferable for Clinicians? a Qualitative Comparison of Two Systems

Two different information systems with respect to their ability to afford clinicians' needs in the chemotherapy medication process were implemented in a large Dutch academic hospital. A commercially available Computerized Physician Order Entry (CPOE) system was not appreciated because clinicians believed that it could not support complex chemotherapy process. Later, a home-grown IT system with the capability of prescribing chemotherapy medications based on standard care protocols was appreciated and fully used by clinicians. We evaluated both systems from their users' perspective to find the sources of clinicians' preference and to trace them back to their Systems Development Life Cycle (SDLC).
The solar Ba${\sf II}$ 4554 Å line as a Doppler diagnostic: NLTE analysis in 3D hydrodynamical model

Instituto de Astrof´isica de Canarias, 38205, C/ V´ia L´actea, s/n, Tenerife, Spain e-mail: khomenko@iac.esReceived date; accepted dateABSTRACTAims. The aim of this paper is to analyse the validity of the Dopplergram and λ-meter techniques for the Dopplerdiagnostics of solar photospheric velocities using the Baii 4554 ˚A line.Methods. Both techniques are evaluated by means of NLTE radiative transfer calculations of the Baii 4554 ˚A line ina three-dimensional hydrodynamical model of solar convection. We consider the cases of spatially unsmeared proﬁlesand the proﬁles smeared to the resolution of ground-based observations.Results. We ﬁnd that: (i) Speckle-reconstructed Dopplergram velocities reproduce the “true” velocities well at heightsaround 300 km, except for intergranular lanes with strong downﬂows where the velocity can be overestimated. (ii)The λ-meter velocities give a good representation of the “true” velocities through the whole photosphere, both underthe original and reduced spatial resolutions. The velocities derived from the inner wing of smeared Baii 4554 ˚A lineproﬁles are more reliable than those for the outer wing. Only under high spatial resolution does the inner wing velocitiescalculated in intergranular regions give an underestimate (or even a sign reversal) compared with the model velocities. (iii) NLTE eﬀects should be taken into account in modelling the Baii 4554 ˚A line proﬁles. Such eﬀects are morepronounced in intergranular regions.Conclusions. Our analysis supports the opinion that the Dopplergram technique applied to the Baii 4554 ˚A line is avaluable tool for the Doppler diagnostics of the middle photosphere around 300 km. The λ-meter technique appliedto this line gives us a good opportunity to “trace” the non-thermal motions along the whole photosphere up to thetemperature minimum and lower chromosphere.Key words.Sun – photosphere: Sun – granulation: line – formation: techniques – spectroscopic – hydrodynamics – radiative transfer