Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced Response Algorithm for Spurious TCP Timeout(ER-SRTO)

Eifel and F-RTO have been reported representative solutions for spurious TCP timeout. However, these algorithms do not work well in case that delay spike and packet loss occur simultaneously. In this paper, we propose ER-SRTO algorithm which detects the packet loss during delay spike and conducts an efficient recovery in the RTO procedure based on ACK sequence number of retransmission packet. Proposed scheme recovers the lost packet without invoking additional loss recovery procedure. Simulation result shows that proposed algorithm outperforms previous ones.
Aurothiomalate and hydroxychloroquine inhibit nitric oxide production in chondrocytes and in human osteoarthritic cartilage

Objectives: Nitric oxide (NO) is a destructive mediator produced by activated chondrocytes. The aim of the present study was to investigate the effect of disease‐modifying anti‐rheumatic drugs (DMARDs) on interleukin‐1β (IL‐1β)‐induced NO production in chondrocyte cultures, and in human osteoarthritic cartilage. Results: Aurothiomalate, hydroxychloroquine, methotrexate and leflunomide inhibited IL‐1β‐induced inducible NO synthase (iNOS) expression and NO production in immortalized H4 chondrocytes, while penicillamine and sulfasalazine had no effect. This can be explained by the fact that the four effective DMARDs also suppressed IL‐1β‐induced activation of nuclear factor kappa B (NF‐κB), which is a crucial transcription factor for iNOS. Aurothiomalate and hydroxychloroquine also inhibited IL‐1β‐induced NO production in OA cartilage whereas methotrexate and leflunomide had no effect. Conclusion: Aurothiomalate and hydroxychloroquine suppressed IL‐1β‐induced NO production in chondrocyte cultures and in OA cartilage. The results suggest an additional anti‐inflammatory mechanism for aurothiomalate and hydroxychloroquine and indicates their possible therapeutic value in the treatment of osteoarthritis (OA).
Tracking of multiple moving speakers with multiple microphone arrays

In this paper we use multiple microphone arrays to fuse the location estimate from each microphone array which yields an improved estimate of the positions and velocities of multiple, simultaneously active, moving speakers based on time delay of arrivals (TDOAs). Our approach: 1) incorporates kinematic information of moving speakers by using an interacting multiple model (IMM) estimator for each speaker in order to constrain the evolution of the location measurements; 2) fuses the location estimates of the same speaker from multiple microphone arrays for better acoustical coverage of the sensed environment, and 3) directly accounts for the measurement origin uncertainty, i.e., which measurement comes from which speaker by using the probabilistic data association (PDA) technique with the IMM estimator. We demonstrate that a network of arrays combined with the estimation technique widely used in multisensor multitarget tracking area provides a consistent and coherent way to reduce the uncertainty and ambiguity of measurements. The effectiveness of our approach is illustrated by extensive simulation study on tracking a single moving speaker and two closely-spaced speakers with a crossing segment in their trajectories.
A framework towards personalisation and active muscle integration in a 3D finite-element neck model for orthopaedic applications

In biomechanics, multi-segmented rigid-body and finite element (FE) models have become an essential tool to explore and quantify the dynamics of human motion through objective parameters. At the neck level, numerous segmental and parametric FE approaches have been used to quantify loads (e.g. to evaluate the design of spinal devices), but only a few studies have explored the influence of subject-specific geometric postural variations on the cervical spine's behaviour (Frechede et al. 2006; Laville et al. 2009). Explorations of the influence of the muscles and the subject-specific complexity of their load sharing on the dynamic stability of the cervical spine are still restricted to rigid-body modelling approaches. At this stage, there is a need for detailed subject-specific models that would allow exploring the links between posture, dynamic stability and muscle function. This study presents the framework and current development of such a model.
Chelation of bismuth by combining desferrioxamine and deferiprone in rats

Consumption and production of bismuth compounds are increasing, however, a little information on the toxic effect and also the effective method in removal of bismuth compounds are available. The present research aimed to characterize the potential efficiency of two chelators after bismuth administration for 55 days following two dose levels of 20 and 40 mg/kg body weight daily to male rats. However, we found abnormalities after bismuth administration in clinical signs, such as body weight, kidneys and liver damages, a black line on gums and skin reactions. Furthermore, the hypothesis that the two chelators might be more efficient as combined therapy than as single therapy in removing bismuth from the body was considered. Along this line, two known chelators deferiprone (1, 2-dimethy1-3-hydroxypyride-4-one, L1) and desferrioxamine (DFO) were chosen and tested in the acute rat model. Chelators were given orally (L1) or intraperitoneally (DFO) as a single or combined therapy for the period of a week. Doses of L1 and DFO were 110 mg/kg body weight in experiments. Bismuth and iron concentrations in various tissues were determined by graphite furnace and flame atomic absorption spectrometry, respectively. The combined chelation therapy results show that DFO and L1 are able to remove bismuth ions from the body, whereas iron concentration returned to the normal level and symptoms are also decreased. DFO was more effective than L1 in reducing bismuth concentration in tissues. The efficiency of DFO + L1 is more than DFO or L1 in removing bismuth from organs. Our results are indicative that the design procedure might be useful for preliminary in-vivo testing of the efficiency of chelating agents. Results of combined chelators’ treatment should be confirmed in a different experimental model before extrapolation to other systems. This testing procedure of course does not provide all the relevant answers for efficiency of chelating agents in bismuth toxicity.
Lower growth factor expression in follicular fluid undergone in-vitro fertilization

Objective This study was performed to identify whether growth and differentiation factor-9 (GDF-9) and transforming growth factor-β1 (TGF-β1) expressions would be lower in the follicular fluid (FF) of those over age 35 who underwent IVF than under age 35. Methods A total of 24 IVF cycles (20 patients) were included in this study. All of patients were stimulated for IVF by the GnRH short protocol and divided into two groups for analysis, according to their age: <35 group (14 cycles, 11 patients) vs. ≥35 group (10 cycles, 9 patients). The expression levels of GDF-9 and TGF-β1 were determined by western blotting and quantitative enzyme-linked immunosorbent assay. Results The numbers of retrieved oocytes and metaphase II oocytes were significantly lower in the ≥35 group. Lower expression of GDF-9 and TGF-β1 by western blotting in the ≥35 group were observed as well. The mean GDF-9 and TGF-β1 levels by enzyme-linked immunosorbent assay were lower in the ≥35 group. The values were 6,850.5±928.4 ng/L vs. 3,333.3±1,089.2 ng/L of GDF-9 (p<0.05) and 3,844.1±571.1 ng/L vs. 2,187.7±754.0 ng/L of TGF-β1 (p<0.05). A negative correlation between GDF-9 and age was observed (r=-0.546, p=0.006). Conclusion GDF-9 and TGF-β1 production from stimulated ovaries during IVF appears to decrease with age.
Dose- and time-dependent effects of TNFα and actinomycin D on cell death incidence and embryo growth in mouse blastocysts

Summary This study was undertaken to obtain information about characteristics of different types of induced apoptosis in preimplantation embryos. Freshly isolated mouse blastocysts were cultured in vitro with the addition of two apoptotic inductors – TNFα and actinomycin D – at various doses and times. The average number of nuclei and the percentage of dead cells were evaluated in treated embryos. Classification of dead cells was based on morphological assessment of their nuclei evaluated by fluorescence microscopy, the detection of specific DNA degradation (TUNEL assay), the detection of active caspase-3 and cell viability assessed by propidium iodide staining. The addition of both apoptotic inductors into culture media significantly increased cell death incidence in blastocysts. Their effects were dose and time dependent. Lower concentrations of inductors increased cell death incidence, usually without affecting embryo growth after 24 h culture. Higher concentrations of inductors caused wider cell damage and also retarded embryo development. In all experiments, the negative effect of actinomycin D on blastomere survival and blastocyst growth was greater than the effect of TNFα. Furthermore, the addition of actinomycin D into culture media increased cell death incidence even after 6 h culture. Differences resulted probably from diverse specificity of apoptotic inductors. The majority of dead cells in treated blastocysts were of apoptotic origin. Morphological and biochemical features of apoptotic cell death induced by both TNFα and actinomycin D were similar and had homologous profile. In blastomeres, similarly to somatic cells, the biochemical pathways of induced apoptosis included activation of caspase-3 and internucleosomal DNA fragmentation.
Methodological characteristics of academic clinical drug trials--a retrospective cohort study of applications to the Danish Medicines Agency 1993-2005.

AIM The aim of this study was to investigate the temporal trends in characteristics of academic clinical drug trials. We here report characteristics on trial methodology. METHODS A review of 386 approved applications of academic clinical drug trials submitted to the Danish Medicines Agency 1993-2005 was carried out. Data on 11 methodological characteristics were collected, e.g. statement of primary endpoint, use of control group, blinding, randomization, method for generation of allocation sequence, monitoring according to the principles of Good Clinical Practice (GCP monitoring) and publication. RESULTS Statement of primary endpoint increased from 60 to 90% of trials (P < 0.0001). Comparing the period before and after implementation of the Clinical Trials Directive in 2004, intention of GCP monitoring increased from 13% to 94%. Control of medicine compliance increased from 42% to 76% (P < 0.0001) among trials with self-administration of the investigational medicinal product. Among controlled trials use of randomization increased from 78% to 94% (P= 0.0063) of trials. Remaining characteristics did not change significantly. In total 68% (264/386) were randomized controlled trials. CONCLUSIONS Our study shows that randomization, definition of primary endpoint, GCP monitoring, and control of medicine compliance form part of a significantly increasing percentage of academic clinical drug trials. This indicates an increase in the quality of academic clinical drug research in Denmark 1993-2005. However, high numbers of unblinded randomized controlled trials and randomized controlled trials utilizing unacceptable methods for generation of allocation sequence emphasize the potential for further improvement of trial methodology.
Viruses and bacteria in acute asthma exacerbations – A GA2LEN‐DARE* systematic review

To cite this article: Papadopoulos NG, Christodoulou I, Rohde G, Agache I, Almqvist C, Bruno A, Bonini S, Bont L, Bossios A, Bousquet J, Braido F, Brusselle G, Canonica GW, Carlsen KH, Chanez P, Fokkens WJ, Garcia‐Garcia M, Gjomarkaj M, Haahtela T, Holgate ST, Johnston SL, Konstantinou G, Kowalski M, Lewandowska‐Polak A, Lødrup‐Carlsen K, Mäkelä M, Malkusova I, Mullol J, Nieto A, Eller E, Ozdemir C, Panzner P, Popov T, Psarras S, Roumpedaki E, Rukhadze M, Stipic‐Markovic A, Todo Bom A, Toskala E, van Cauwenberge P, van Drunen C, Watelet JB, Xatzipsalti M, Xepapadaki P, Zuberbier T. Viruses and bacteria in acute asthma exacerbations – A GA2LEN‐DARE systematic review. Allergy 2011; 66: 458–468.
Role of ADDUCIN Gly460Trp, ACE I/D and AGT M235T Gene Polymorphisms in Genetic Susceptibility to Diabetic Nephropathy

Diabetes mellitus is a metabolic disease with a high incidence of morbidity and mortality lowering the quality of life with acute and chronic complications and it needs to be followed up and treated throughout the lifespan. Concordant with the frequency of DM and the increase in the length of life frequency of DNP is also increased. The I allele of the ACE I/D polymorphism, AGT M235T’s T allele and ADD G460W’s W allele presence are purported to present a predisposition to DNP. In our study we aimed to investigate the effect of the AGT M235T, ACE I/D and ADD 460W polymorphisms in the development of DNP in patients with diabetes mellitus. The study group consisted of 194 patients with Diabetic nephropathy and the control group contained 100 DM patients. In the diabetic group the DD genotype of the ACE I/D polymorphism was 54 (54.0%) and the D allele was 69.0% and in the nephropathy group II genotype of the ID were 78 (40.2%) and 51 (26.3%) and the I allele was 46.4 respectively and the presence of the I allele was associated with the presence of nephropathy. There was no significance between the genotypes in the presence of a coexistence of AGT M235T and ACE I/D polymorphisms between the groups the MD alleles (42%) demonstrated significance in the diabetic and the T/I alleles (28.1) demonstrated significance in the nephropathy group. In the ADD G640W polymorphism on its own, subjects having GG (77.3%) and WW (7.7%) genotypes (p=0.025) might have been predisposed to nephropathy however when in combination with the ACE I/D, the presence of the DD/GG (45%) in the diabetic group and the presence of the ID/GG (29.9%) and II/GG (19.6%) combination in the DNP group were statistically significant. The D/G (64%) alleles were significant in the diabetic and the I/G (36.6) alleles were significant in the DNP groups respectively. As a conclusion we think that the II-ID/GG genotype and the I/G alleles in the presence of the ACE-ADD combination and TT/ID genotype and T/I alleles in the ACE-AGT combination may be effective in the predisposition of the diabetic patients to nephropathy.
Steroid Receptor RNA Activator (SRA) Modification by the Human Pseudouridine Synthase 1 (hPus1p): RNA Binding, Activity, and Atomic Model

The most abundant of the modified nucleosides, and once considered as the “fifth” nucleotide in RNA, is pseudouridine, which results from the action of pseudouridine synthases. Recently, the mammalian pseudouridine synthase 1 (hPus1p) has been reported to modulate class I and class II nuclear receptor responses through its ability to modify the Steroid receptor RNA Activator (SRA). These findings highlight a new level of regulation in nuclear receptor (NR)-mediated transcriptional responses. We have characterised the RNA association and activity of the human Pus1p enzyme with its unusual SRA substrate. We validate that the minimal RNA fragment within SRA, named H7, is necessary for both the association and modification by hPus1p. Furthermore, we have determined the crystal structure of the catalytic domain of hPus1p at 2.0 Å resolution, alone and in a complex with several molecules present during crystallisation. This model shows an extended C-terminal helix specifically found in the eukaryotic protein, which may prevent the enzyme from forming a homodimer, both in the crystal lattice and in solution. Our biochemical and structural data help to understand the hPus1p active site architecture, and detail its particular requirements with regard to one of its nuclear substrates, the non-coding RNA SRA.
Role of TLR4  rs4986790A>G and rs4986791C>T Polymorphisms in the Risk of Inflammatory Bowel Disease

Objective. The present meta-analysis investigated the contribution of TLR4 rs4986790A>G and rs4986791C>T genetic polymorphisms in increasing the risk of inflammatory bowel disease (IBD). Methods. Databases were searched using a combination of keywords related to TLR4 and IBD. Relevant studies were selected based on strict inclusion and exclusion criteria. Meta-analysis of the data extracted from the selected studies was performed using CMA 2.0 statistical analysis software. Results. Out of the 70 studies retrieved by database search, only 13 studies were eligible for inclusion in this meta-analysis and these 13 studies contained a total number of 4409 IBD patients and 5693 healthy controls. The meta-analysis results demonstrated that TLR4 rs4986790A>G polymorphism is associated with an increased risk of IBD (allele model: OR = 1.268, 95% CI = 1.124~1.431, and P < 0.001; dominant model: OR = 1.240, 95% CI = 1.090~1.409, and P = 0.001). Similarly, TLR4 rs4986791C>T polymorphism also conferred an increased risk of IBD (allele model: OR = 1.259, 95% CI = 1.092~1.453, and P = 0.002; dominant model: OR = 1.246, 95% CI = 1.072~1.447, and P = 0.004). Conclusion. Our meta-analysis results demonstrate that TLR4 rs4986790A>G and rs4986791C>T genetic polymorphisms are associated with the etiopathogenesis of IBD.
Determinants of Cardiac Catheterization Use in Older Medicare Patients With Acute Myocardial Infarction

Background—Cardiac catheterization is substantially underused among higher-risk patients with acute myocardial infarction (AMI) with appropriate indications but overused among patients with inappropriate indications. We sought to determine the importance of anticipated benefit and anticipated harm on the use of cardiac catheterization among older patients with AMI. Methods and Results—We performed an analysis of Medicare fee-for-service beneficiaries hospitalized with an AMI between 1998 and 2001. Multivariate models were developed to determine relative importance of anticipated benefit (baseline cardiovascular risk), anticipated harm (bleeding risk, comorbidities), and demographic factors (age, sex, race, regional invasive intensity) in predicting cardiac catheterization use within 60 days of AMI admission. Analyses were stratified by American College of Cardiology/American Heart Association class I or II as appropriate, and class III as inappropriate. Determinants of reduced likelihood of cardiac catheterization among 42 241 AMI patients with appropriate indications included (in order of importance) older age (likelihood &khgr;2=1309.5), higher bleeding risk score (likelihood &khgr;2=471.2), more comorbidities (likelihood &khgr;2=276.6), female sex (likelihood &khgr;2=162.9), hospitalization in low (likelihood &khgr;2=67.9) or intermediate intensity invasive regions (likelihood &khgr;2=22.4) (all P<0.001), and baseline cardiovascular risk (likelihood &khgr;2=6.4, P=0.01). Among 2398 AMI patients with inappropriate indications, significant determinants of greater procedure likelihood included younger age, male sex, lower bleeding risk score, and fewer comorbidities. Conclusions—Regardless of the procedure indication, the decision to perform cardiac catheterization in this population appears largely driven by demographic factors and potential harm rather than potential benefit of the procedure.
The Impact of Anxiety-Inducing Distraction on Cognitive Performance: A Combined Brain Imaging and Personality Investigation

Background Previous investigations revealed that the impact of task-irrelevant emotional distraction on ongoing goal-oriented cognitive processing is linked to opposite patterns of activation in emotional and perceptual vs. cognitive control/executive brain regions. However, little is known about the role of individual variations in these responses. The present study investigated the effect of trait anxiety on the neural responses mediating the impact of transient anxiety-inducing task-irrelevant distraction on cognitive performance, and on the neural correlates of coping with such distraction. We investigated whether activity in the brain regions sensitive to emotional distraction would show dissociable patterns of co-variation with measures indexing individual variations in trait anxiety and cognitive performance. Methodology/Principal Findings Event-related fMRI data, recorded while healthy female participants performed a delayed-response working memory (WM) task with distraction, were investigated in conjunction with behavioural measures that assessed individual variations in both trait anxiety and WM performance. Consistent with increased sensitivity to emotional cues in high anxiety, specific perceptual areas (fusiform gyrus - FG) exhibited increased activity that was positively correlated with trait anxiety and negatively correlated with WM performance, whereas specific executive regions (right lateral prefrontal cortex - PFC) exhibited decreased activity that was negatively correlated with trait anxiety. The study also identified a role of the medial and left lateral PFC in coping with distraction, as opposed to reflecting a detrimental impact of emotional distraction. Conclusions These findings provide initial evidence concerning the neural mechanisms sensitive to individual variations in trait anxiety and WM performance, which dissociate the detrimental impact of emotion distraction and the engagement of mechanisms to cope with distracting emotions. Our study sheds light on the neural correlates of emotion-cognition interactions in normal behaviour, which has implications for understanding factors that may influence susceptibility to affective disorders, in general, and to anxiety disorders, in particular.
In Situ Scanning Tunneling Microscopy of Polycrystalline Platinum Electrodes under Potential Control Copper Electrodeposition and Pyrrole Electropolymerization

The surface changes of Pt electrodes immersed in solution under potential control were studied by scanning tunneling microscopy. Various structures were observed on a polished, flame-annealed-quenched polycrystalline electrode. Extended cycling of the electrode in 1M H2SO4 between the regions where an adsorbed oxide film forms and is removed causes significant roughening of the electrode surface. The electrodeposition of copper on polycrystalline Pt and of polypyrrole on a Pt film on mica was also investigated. The scanning tunneling microscope (STM) allows very high resolution (atomic or near-atomic) examination of the surfaces of conductive or semiconductive substrates (1, 2). Although originally mainly applied to samples in a vacuum or a gaseous environment, this technique has been used to investigate various substrates immersed in aqueous and nonaqueous solutions (3-9). We have further demonstrated the in situ study of anodic dissolution of nickel electrodes in sulfuric acid solution under external polarization conditions and open-circuit corrosion of stainless steel in aqueous chloride media (10).