Miracle-dz/UniFAR-FTUs huggingface dataset:
A Salmonella Virulence Factor Activates the NOD1/NOD2 Signaling Pathway

ABSTRACT The invasion-associated type III secretion system (T3SS-1) of Salmonella enterica serotype Typhimurium (S. Typhimurium) activates the transcription factor NF-κB in tissue culture cells and induces inflammatory responses in animal models through unknown mechanisms. Here we show that bacterial delivery or ectopic expression of SipA, a T3SS-1-translocated protein, led to the activation of the NOD1/NOD2 signaling pathway and consequent RIP2-mediated induction of NF-κB-dependent inflammatory responses. SipA-mediated activation of NOD1/NOD2 signaling was independent of bacterial invasion in vitro but required an intact T3SS-1. In the mouse colitis model, SipA triggered mucosal inflammation in wild-type mice but not in NOD1/NOD2-deficient mice. These findings implicate SipA-driven activation of the NOD1/NOD2 signaling pathway as a mechanism by which the T3SS-1 induces inflammatory responses in vitro and in vivo. IMPORTANCE Salmonella enterica serotype Typhimurium (S. Typhimurium) deploys a type III secretion system (T3SS-1) to induce intestinal inflammation and benefits from the ensuing host response, which enhances growth of the pathogen in the intestinal lumen. However, the mechanisms by which the T3SS-1 triggers inflammatory responses have not been resolved. Here we show that the T3SS-1 effector protein SipA induces NF-κB activation and intestinal inflammation by activating the NOD1/NOD2 signaling pathway. These data suggest that the T3SS-1 escalates innate responses through a SipA-mediated activation of pattern recognition receptors in the host cell cytosol. Salmonella enterica serotype Typhimurium (S. Typhimurium) deploys a type III secretion system (T3SS-1) to induce intestinal inflammation and benefits from the ensuing host response, which enhances growth of the pathogen in the intestinal lumen. However, the mechanisms by which the T3SS-1 triggers inflammatory responses have not been resolved. Here we show that the T3SS-1 effector protein SipA induces NF-κB activation and intestinal inflammation by activating the NOD1/NOD2 signaling pathway. These data suggest that the T3SS-1 escalates innate responses through a SipA-mediated activation of pattern recognition receptors in the host cell cytosol.
Constructing a user-friendly GA-based fuzzy system directly from numerical data

This paper proposes a novel genetic algorithms (GA)-based algorithm to construct a user-friendly fuzzy system for approximating an unknown system with a satisfactory degree of accuracy. In the algorithm, the adequate number of fuzzy rules, the adequate number of membership functions of each input variable, and the parameters of membership functions will be determined automatically; in addition, the dummy input variables will be detected and discarded. Finally, several typical examples are illustrated to show the effectiveness of the algorithm.
Cancer as a mitochondrial metabolic disease

Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes. This view persists despite the numerous inconsistencies associated with the somatic mutation theory. In contrast to the somatic mutation theory, emerging evidence suggests that cancer is a mitochondrial metabolic disease, according to the original theory of Otto Warburg. The findings are reviewed from nuclear cytoplasm transfer experiments that relate to the origin of cancer. The evidence from these experiments is difficult to reconcile with the somatic mutation theory, but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease.
Effects of germination conditions on ascorbic acid level and yield of soybean sprouts

The effects of light illumination on the ascorbic acid content and growth of soybean sprouts were investigated. Among the six light qualities studied, ultraviolet light had the highest promoting effect on the ascorbic acid content in soybean sprouts, increasing it by 77.0% compared with the darkness control, while red light had the highest promoting effect on the growth of soybean sprouts, increasing the total fresh weight by 16.6% compared with the darkness control. Experiments with different durations of ultraviolet and red light illumination in a day showed that 12 h ultraviolet (500 Lx) and 12 h red (1000 Lx) light diurnal cycles had the highest promoting effects on both the ascorbic acid level and fresh weight of soybean sprouts, increasing the ascorbic acid content and total fresh weight by 78.7 and 17.4% respectively compared with the darkness control. The results indicated that germination of soybeans under 12 h ultraviolet and 12 h red light diurnal cycles was an effective process for increasing the yield and enhancing the nutritional quality of soybean sprouts.
EULERIAN MULTI-FLUID MODELS : MODELING AND NUMERICAL METHODS

In this contribution we propose a general presentation of Eulerian multi-ﬂuid modeling and numerical methods for the simulation of polydisperse evaporating sprays. By spray, we denote a cloud of spherical liquid droplets of various sizes ranging from submicronic scales up to several hundred microns which interact with the carrier gaseous phase and among themselves. We deal with sprays for which the physics of such a two-phase ﬂow is governed at the “kinetic” level, also called mesoscopic level, by a Williams-Boltzmann spray equation, where the elementary phenomena such as evaporation, heating, coalescence and secondary break-up can be described properly. Our ob jective is to provide a hierarchy of models of Eulerian type with two main criteria : 1- to take into account accurately the polydispersion of the spray, that is the large size spectrum, as well as size-conditioned dynamics, evaporation and heating, 2- to keep a rigourous link with the Williams-Boltzmann spray equation at the mesoscopic level of description. We start with the original multi-ﬂuid model where the polydispersion is resolved by discretizing the size phase space into intervals, also called sections in relation to the original work of Greenberg and Tambour. We present the fundamentals of the model, the associated precise set of related closure assumptions as well as its implication on the mathematical structure of solutions. We provide robust numerical methods able to cope with the potential presence of singularities and a set of validations showing the eﬃciency of the model and of the related numerical methods. This approach is very robust but encounters two diﬃculties : 1- in order to accurately resolve evaporation and size conditioned dynamics in phase space, it requires a high number of size intervals, 2- for ﬁnite Stokes numbers and large Knudsen numbers, it fails to reproduce droplet crossing tra jectories since it relies on a hydrodynamic local velocity equilibrium. We thus present recent studies based on high order moment methods which allow to overcome these two diﬃculties. Then, the models are validated by comparisons with experimental measurements in the conﬁguration of pulsated free jets with polydisperse spray injection, a dedicated well-controled environment with coupled Laser diagnostics. We conclude this lecture with a chapter on the computational multi-ﬂuid dynamics and prove that the proposed models and related numerical methods and algorithms are well-suited for 2D and 3D simulations. They prove to be very accurate versus a Lagragian approach and eventually involve a small amount of numerical diﬀusion as a consequence of a precise choice of algorithms. Their ability for high performance computing on parallel architecture with dedicated algorithms is also demonstrated. In the framework of this Lecture Series, it provides a set of very interesting tools for the purpose of simulating nanoparticles in ﬂuid ﬂows.
Socioeconomic position and the risk of spontaneous abortion: a study within the Danish National Birth Cohort

Objectives To investigate the relationship between different indicators of socioeconomic position and the risk of spontaneous abortion. Design Cohort study. Setting 1996–2002, Denmark. Participants All first time participants, a total of 89 829 pregnant women, enrolled in the Danish National Birth Cohort were included in the present study. Overall, 4062 pregnancies ended in spontaneous abortion. Information on education, income and labour market attachment in the year before pregnancy was drawn from national registers. Main outcome measure Spontaneous abortion, that is, fetal death within the first 22 weeks of pregnancy, was the outcome of interest. The authors estimated HRs of spontaneous abortion using Cox regression analysis with gestational age as the underlying time scale. Results Women with <10 years of education had an elevated risk of spontaneous abortion when compared with women with >12 years of education (HR 1.19 (95% CI 1.05 to 1.34)). The HR estimates for the four lowest income quintiles were all increased (HRs between 1.09 and 1.15) as compared with the upper quintile but did not differ considerably from each other. In general, no statistically significant association was found between labour market attachment and the risk of spontaneous abortion; however, the group of women on disability pension had an increased HR of spontaneous abortion when compared with women who were employed (HR 1.32 (95% CI 0.82 to 2.13)). Conclusions Educational level and income were inversely associated with the risk of spontaneous abortion. As these factors most likely are non-causally related to spontaneous abortion, the findings indicate that factors related to social position, probably of the environmental and behavioural type, may affect spontaneous abortion risk. The study highlights the need for studies addressing such exposures in order to prevent spontaneous abortions.
Comparison of five systems of classification of diabetic foot ulcers and predictive factors for amputation

Diabetes mellitus is a common metabolic disorder. Among various complications, diabetic neuropathy and peripheral vascular disorders are closely associated with diabetic foot ulcers (DFUs). Lower extremity ulcers and amputations are ongoing problems among individuals with diabetes. There are several classification systems for DFUs; however, no prognostic system has to date been accepted as the gold standard or the optimum prediction tool for amputations. A retrospective study was designed. Demographic data and baseline laboratory data were gathered and scored or evaluated using five representative DFU classification systems. These included (i) the diabetic ulcer severity score (DUSS); (ii) University of Texas (UT) diabetic wound classification; (iii) Meggitt–Wagner classification; (iv) depth of the ulcer, extent of bacterial colonisation, phase of ulcer and association aetiology (DEPA) scoring system; and (v) site, ischaemia, neuropathy, bacterial infection and depth (SINBAD) score. Finally, a statistical analysis was performed. A total of 137 patients were included in this study. During the follow‐up, DFU had healed in 51·1% of subjects and 48·9% of the individuals underwent lower extremity amputations (LEAs). In a univariable logistic regression analysis, history of previous DFU, hypertension, neuropathy, haemoglobin, C‐reactive protein (CRP) and ankle‐brachial index (ABI) showed a statistically significant difference between the healed group and the LEA group. Moreover, the stages, grades or overall prognostic ability of all five classifications were highly associated with the overall occurrence of LEA. On multivariable logistic regression analysis of the risk of LEA, all classifications showed a significant positive trend with an increased number of amputations. All the five classification systems exhibited high sensitivity, specificity, classification accuracy, positive predictive, negative predictive and area under the curve (AUC) values. They showed substantial accuracy and their main variables were associated with LEA occurrence. The Wagner and UT systems, although they are relatively simple to assess, were better predictors of LEA.
A recombinant Leishmania chagasi antigen that stimulates cellular immune responses in infected mice

Cellular immune mechanisms resulting in gamma interferon production are critical for protection against visceral leishmaniasis. Antigens stimulating T-cell responses are likely present in the intracellular amastigote form of the parasite, since this is the form found in a mammalian host. To identify T-cell antigens of Leishmania chagasi, the parasite causing South American visceral leishmaniasis, we used a double antibody-T-cell technique to screen an amastigote cDNA library. One cDNA selected (Lcr1) encodes an antigen that stimulated proliferation of splenic T lymphocytes from infected mice that were either resistant (C3H.HeJ) or susceptible (BALB/c) to L. chagasi infection. The Lcr1 cDNA contains four highly divergent 201-bp repeats homologous to the 204-bp repeat of a Trypanosoma cruzi flagellar antigen gene. Results are consistent with a single copy of the Lcr1 gene producing an mRNA of > 10 kb and a protein of > 200 kDa. Recombinant Lcr1, cloned adjacent to polyhistidine and purified on a nickel affinity column, stimulated gamma interferon but not interleukin-4 (IL-4), IL-5, or IL-10 secretion by T-cell-enriched splenocytes from either susceptible or resistant mice during L. chagasi infection. Immunization with Lcr1 partially protected BALB/c mice against challenge with L. chagasi, indicating the utility of the double screening approach in selecting relevant T-cell antigens.
Dissociation Among Swedish Adolescents and the Connection to Trauma: An Evaluation of the Swedish Version of Adolescent Dissociative Experience Scale

The purpose of this study was to investigate the psychometric properties of the Swedish version of Adolescent Dissociative Experience Scale (A-DES), dissociative symptoms among Swedish adolescents, and dissociative symptoms connected to trauma and sexual and physical abuse. A normative group of 400 adolescents aged 12 to 19 years and a clinical group of 20 adolescents with known experienced trauma were given A-DES. A test-retest procedure was conducted with 90 subjects from the normative group. The results showed good reliability, internal consistency and test-retest. Factor analysis in the normative sample (N = 400) resulted in a one factor solution. Correlation between A-DES and other measures of dissociation was high (r = .86). Significant differences for the total sum of A-DES were found in the normative group between adolescents with and without self-reported trauma and between the normative group and the clinical group with known experienced trauma. The Swedish version of A-DES was shown to be a screening instrument with satisfactory psychometric qualities and the capability of capturing dissociative symptoms in adolescents with self-reported trauma as well as clinical cases with identified trauma.
A systematic review of model-based economic evaluations of diagnostic and therapeutic strategies for lower extremity artery disease

Summary Lower extremity artery disease (LEAD) is a sign of wide spread atherosclerosis also affecting coronary, cerebral and renal arteries and is associated with increased risk of cardiovascular events. Many economic evaluations have been published for LEAD due to its clinical, social and economic importance. The aim of this systematic review was to assess modelling methods used in published economic evaluations in the field of LEAD. Our review appraised and compared the general characteristics, model structure and methodological quality of published models. Electronic databases MEDLINE and EMBASE were searched until February 2013 via OVID interface. Cochrane database of systematic reviews, Health Technology Assessment database hosted by National Institute for Health research and National Health Services Economic Evaluation Database (NHSEED) were also searched. The methodological quality of the included studies was assessed by using the Philips’ checklist. Sixteen model-based economic evaluations were identified and included. Eleven models compared therapeutic health technologies; three models compared diagnostic tests and two models compared a combination of diagnostic and therapeutic options for LEAD. Results of this systematic review revealed an acceptable to low methodological quality of the included studies. Methodological diversity and insufficient information posed a challenge for valid comparison of the included studies. In conclusion, there is a need for transparent, methodologically comparable and scientifically credible modelbased economic evaluations in the field of LEAD. Future modelling studies should include clinically and economically important cardiovascular outcomes to reflect the wider impact of LEAD on individual patients and on the society.
Parameter Estimation Methods for Five-Limb Magnetic Core Model

The majority of transformer model realizations used for power system transient simulations have some significant deficiencies, particularly related to the transformer core implementation. They either do not include the multilimb topology of the iron core, come upon some numerical stability issues, have limited use for three-phase transformers, or lack a complete leakage representation. Detailed consideration of the saturation effects is essential for accurate transient simulation of ferroresonance, excitation, inrush currents, half-cycle saturation, and similar phenomena. A recently published topologically correct core model, valid for low- and mid-frequency ranges, addresses this need. This paper details the parameter estimation methods developed for the five-legged core of this model.
High Expression Levels of X-Linked Inhibitor of Apoptosis Protein and Survivin Correlate with Poor Overall Survival in Childhood de Novo Acute Myeloid Leukemia

Purpose: Apoptosis-related proteins are important molecules for predicting chemotherapy response and prognosis in adult acute myeloid leukemia (AML). However, data on the expression and prognostic impact of these molecules in childhood AML are rare. Experimental Design: Using flow cytometry and Western blot analysis, we, therefore, investigated 45 leukemic cell samples from children with de novo AML enrolled and treated within the German AML-BFM93 study for the expression of apoptosis-regulating proteins [CD95, Bcl-2, Bax, Bcl-xL, procaspase-3, X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis protein–1 (cIAP-1), survivin]. Results: XIAP (P < 0.002) but no other apoptosis regulators showed maturation-dependent expression differences as determined by French-American-British (FAB) morphology with the highest expression levels observed within the immature M0/1 subtypes. XIAP (P < 0.01) and Bcl-xL (P < 0.01) expression was lower in patients with favorable rather than intermediate/poor cytogenetics. After a mean follow-up of 34 months, a shorter overall survival was associated with high expression levels of XIAP [30 (n = 10) versus 41 months (n = 34); P < 0.05] and survivin [27 (n = 10) versus 41 months (n = 34); P < 0.05]. Conclusions: We conclude that apoptosis-related molecules are associated with maturation stage, cytogenetic risk groups, and therapy outcome in childhood de novo AML. The observed association of XIAP with immature FAB types, intermediate/poor cytogenetics, and poor overall survival should be confirmed within prospective pediatric AML trials.
Integration of the tricarboxylic acid (TCA) cycle with cAMP signaling and Sfl2 pathways in the regulation of CO2 sensing and hyphal development in Candida albicans

Morphological transitions and metabolic regulation are critical for the human fungal pathogen Candida albicans to adapt to the changing host environment. In this study, we generated a library of central metabolic pathway mutants in the tricarboxylic acid (TCA) cycle, and investigated the functional consequences of these gene deletions on C. albicans biology. Inactivation of the TCA cycle impairs the ability of C. albicans to utilize non-fermentable carbon sources and dramatically attenuates cell growth rates under several culture conditions. By integrating the Ras1-cAMP signaling pathway and the heat shock factor-type transcription regulator Sfl2, we found that the TCA cycle plays fundamental roles in the regulation of CO2 sensing and hyphal development. The TCA cycle and cAMP signaling pathways coordinately regulate hyphal growth through the molecular linkers ATP and CO2. Inactivation of the TCA cycle leads to lowered intracellular ATP and cAMP levels and thus affects the activation of the Ras1-regulated cAMP signaling pathway. In turn, the Ras1-cAMP signaling pathway controls the TCA cycle through both Efg1- and Sfl2-mediated transcriptional regulation in response to elevated CO2 levels. The protein kinase A (PKA) catalytic subunit Tpk1, but not Tpk2, may play a major role in this regulation. Sfl2 specifically binds to several TCA cycle and hypha-associated genes under high CO2 conditions. Global transcriptional profiling experiments indicate that Sfl2 is indeed required for the gene expression changes occurring in response to these elevated CO2 levels. Our study reveals the regulatory role of the TCA cycle in CO2 sensing and hyphal development and establishes a novel link between the TCA cycle and Ras1-cAMP signaling pathways.
Effect of Antiplatelet Therapy for Endovascular Coiling in Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— Antiplatelets are frequently used during or after endovascular coiling of aneurysm in patients with subarachnoid hemorrhage (SAH). This strategy is based on uncontrolled case series including also patients with unruptured aneurysms or other lesions. We collected data on effectiveness of antiplatelets in patients with SAH. Methods— All 43 participating centers in the International Subarachnoid Aneurysm Trial (ISAT) were sent a questionnaire whether they never, sometimes, or always prescribed antiplatelets during or after coiling. Based on individual patient data, the relative risks (RRs) of coiling versus clipping were calculated separately for patients treated in hospitals with standard prescription during or after coiling versus patients treated in hospitals with no standard prescription of antiplatelets. We calculated ratios of RRs for standard versus not standard prescription of antiplatelets during coiling and for standard versus not standard prescription after coiling. Results— Nineteen centers responded, representing 1422 (66%) of the 2143 ISAT patients. Antiplatelets were standard prescribed during coiling in 2 responding centers (8% of coiled patients) and after coiling in 6 centers (24%). For poor outcome at 2 months of coiling versus clipping the RR was 0.82 (95% CI: 0.45 to 1.49) in hospitals with a policy of antiplatelet prescription during coiling versus 0.66 (95% CI: 0.55 to 0.78) in those without such policy (ratio of RR’s 1.24, P=0.56). The ratio of RRs for 1-year outcome was 1.01 (P=0.89) for antiplatelet use during coiling and 1.00 (P=0.77) for use after coiling. Conclusion— The results of this study do not support the assumption that antiplatelets during or after endovascular coiling improve outcome in patients with SAH.