Miracle-dz/UniFAR-FTUs huggingface dataset:
Idiosyncratic Liver Injury: Challenges and Approaches

Clinical presentations of drug-induced liver injury (DILI) cover essentially the entire spectrum of known liver diseases. However, in the last 8 years the form of liver injury that has most frequently resulted in labeling restrictions is idiosyncratic hepatocellular injury leading to acute liver failure. This rare form of DILI has a characteristic clinical presentation that includes an acute onset after uneventful treatment with drug for weeks to months. Serum alanine aminotransferase rises to very high levels and the appearance of jaundice indicates a high mortality even if the therapy is discontinued. Drugs that can cause this type of injury almost always are associated with frequent (2–15% of all treated patients) and minor serum aminotransferase elevations. These elevations are believed to reflect true liver injury, but often reverse even if drug therapy is continued. The basis for this “adaptation” is not known, as is why some patients do not adapt and develop progressive liver injury. Understanding how drugs cause severe idiosyncratic hepatocellular toxicity has been frustrated by the lack of good preclinical models. Indeed, because these events occur so rarely, the vast majority of humans are not good models. Studies of genomic DNA from affected individuals should provide important insight but not the complete answer because environmental factors almost certainly contribute to individual susceptibility. The most fruitful approach may therefore lie in focused and well-controlled phenotype/genotype studies of the rare patients who have survived this type of injury. The National Institute of Diabetes and Digestive and Kidney Diseases of The National Institutes of Health has recently sponsored a cooperative agreement (UO1) to create a Drug Induced Liver Injury Network (DILIN). DILIN consists of University of Michigan, Indiana University, University of Connecticut, University of California, San Francisco, University of North Carolina, and Duke University. This network should provide heretofore missing resources required to address the problem.
Estudio de la relación genética entre los caracteres facilidades de parte materna y fertilidad de la hembra en el ganado vacuno lechero de la CAPV

La mejora genética tiene como objetivo modificar el mérito genético en las generaciones siguientes para que los animales produzcan de forma más eficiente. En el caso del vacuno de leche, los caracteres que influyen en la eficiencia de producción pueden diferenciarse principalmente entre caracteres de producción (leche y carne) y caracteres funcionales. El término de caracteres funcionales se utiliza para resumir las características del animal que incrementan la eficiencia de producción, no aumentando los ingresos (outputs) sino reduciendo los costes (inputs) (GROEN et al, 1997). GROEN y colaboradores (GROEN et al, 1997) recomendaron el estudio de caracteres como salud, facilidad de parto, fertilidad, eficiencia en la utilización del alimento y adaptabilidad al ordeño dentro de la categoría de caracteres funcionales. Actualmente, como consecuencia del sistema de cuotas y del descenso del precio de la leche, el sector del vacuno de leche comienza a demandar la inclusión dentro del objetivo de selección de dichos caracteres funcionales con el fin de incrementar la rentabilidad (ALENDA y CARABAÑO, 2002). Los ganaderos no reclaman un animal más productivo, sino que buscan un animal que mantenga su producción y que no de problemas. En el caso particular del carácter facilidad de parto, la reducción de la incidencia de partos distócicos en la explotación tiene importancia tanto desde un punto de vista productivo como reproductivo, ya que la presencia de una distocia en la explotación induce a pérdidas económicas notables, no sólo asociadas a la disminución de la producción, pues puede ocasionar la muerte de la vaca y/o el ternero, disminuir la fertilidad, aumentar los gastos veterinarios y los requerimientos de mano de obra (DEMATAWEWA y BERGER, 1997; 1998). En la Comunidad Autónoma del País Vasco, la valoración genética del carácter facilidad de parto se puso en marcha en el año 1995 (ALDAY y UGARTE, 1997). Desde entonces, el sistema de evaluación genética ha sufrido cambios y mejoras tanto en la recogida del dato como en el análisis y presentación de los resultados (LÓPEZ DE MATURANA et al, 2003). Sin embargo, las relaciones de este carácter con otros caracteres funcionales como la fertilidad no han sido abordadas aún. El presente estudio tiene como objetivo analizar la posible relación genética entre los caracteres de facilidad de parto materna (FPM) y fertilidad de la hembra en el siguiente ciclo reproductivo dentro de la población frisona de la CAPV.
Configurations and performance evaluations for a long-delay multipath interference based on the combinational use of an adaptive array antenna and multipath equalizers

Long-delay multipath interference is defined as a delayed signal located outside the guard interval of OFDM systems. An adaptive array antenna is often used to suppress long-delay multipath interference; however, the performance degrades when the desired and interference signals come from nearly the same direction. In these situations, a multipath equalizer in the time domain is very effective for suppressing the interference signal. In this paper, we propose three configurations based on a combinational use of an adaptive array antenna and a multipath equalizer as a remedy for long-delay multipath interference. We evaluated the performance using a computer simulation. The results show that excellent performance can be achieved even when the directions of desired and interference signals are close as well as when the interference signal comes from arbitrary directions.
Familial syndrome combining deaf-mutism, stuppled epiphyses, goiter and abnormally high PBI: possible target organ refractoriness to thyroid hormone.

Abstract The occurrence of a bizarre familial syndrome combining deaf-mutism, stippled epiphyses, goiter and abnormally high PBI in 2 of 6 children of a consanguineous marriage is described. Mean PBI levels were 14 and 21 μg/100 ml; BEI 9 and 15 μg/100 ml; T4-by-column 11 and 14 μg/100 ml; 24-hr 131I uptake 49 and 70%; 24-hr PB13lI conversion ratios 40 and 41%; thyro-binding index 0.81 and 0.93; TBG 17 and 20 μg/100 ml; antithyroglobulin titer less than 1:16. Potassium perchlorate discharge test was normal. Iodine metabolism studied in one subject revealed thyroid iodine clearance of 24 ml/min and renal clearance of 26 ml/min. Urinary iodide excretion was 294 υg/day, and PB131I was over 70% as T4. The T4 was identified on paper chromatography in 3 solvent systems. The free thyroxine level was 4.9 mμg/100 ml. An infant of 8 weeks had a mean PBI of 19.3 μg/100 ml, TBG of 15.8 μg/100 ml, and presumably also has the syndrome. Another sib had a mean PBI of 11 μg/100 ml. Two sibs and the parents are normal. A h.
Designing multivalent probes for tunable superselective targeting

Significance A basic requirement in biomedical research is the ability to specifically target cells and tissues. Targeting typically relies on the specific binding of a “ligand” on a tailor-made probe to a “receptor” on the desired cell/tissue. Conventional probes efficiently distinguish a biological entity displaying the receptor from others that do not, but exhibit limited selectivity when the entities to be distinguished display a given receptor at different densities. Multivalent probes that bind several receptors simultaneously potentially can sharply discriminate between different receptor densities. We demonstrate how such “superselective” binding can be tuned through probe design to target a desired receptor density, and thus lay the foundation for the rational design of a new generation of analytical, diagnostic, and therapeutic probes. Specific targeting is common in biology and is a key challenge in nanomedicine. It was recently demonstrated that multivalent probes can selectively target surfaces with a defined density of surface binding sites. Here we show, using a combination of experiments and simulations on multivalent polymers, that such “superselective” binding can be tuned through the design of the multivalent probe, to target a desired density of binding sites. We develop an analytical model that provides simple yet quantitative predictions to tune the polymer’s superselective binding properties by its molecular characteristics such as size, valency, and affinity. This work opens up a route toward the rational design of multivalent probes with defined superselective targeting properties for practical applications, and provides mechanistic insight into the regulation of multivalent interactions in biology. To illustrate this, we show how the superselective targeting of the extracellular matrix polysaccharide hyaluronan to its main cell surface receptor CD44 is controlled by the affinity of individual CD44–hyaluronan interactions.
What once was lost, now is found: Restoration of hepatitis B–specific immunity after treatment of chronic hepatitis B

High viral and/or antigen load may be an important cause of the T cell hyporesponsiveness to hepatitis B virus (HBV) antigens that is often observed in patients with chronic HBV infection. Reduction of viral and antigen load by lamivudine treatment represents an ideal model for investigating this hypothesis. HLA class II restricted T cell responses and serum levels of HBV-DNA, HBsAg, and HBeAg were studied before and during lamivudine treatment in 12 patients with hepatitis B e antigen positive chronic active hepatitis B to assess possible correlations between viral and/or antigen load and vigor of the T cell response. Cell proliferation to HBV nucleocapsid antigens and peptides and frequency of circulating HBV nucleocapsid-specific T cells were assessed to characterize CD4-mediated responses. A highly significant enhancement of the CD4-mediated response to HBV nucleocapsid antigens was already detectable in most patients 7-14 d after the start of lamivudine treatment. This
Treatment of Pulmonary Coccidioidomycosis after Successful Hepatitis C Therapy in a Patient with Fluconazole Induced Hepatotoxicity

A patient with hepatitis C infection and cavitary pulmonary coccidioidomycosis is reported. Treatment of hepatitis C was associated with resolution of fluconazole-induced hepatotoxicity. Successful treatment of hepatitis C enabled the patient to tolerate increaseing doses of fluconazole. This case highlights that hepatic toxicity of fluconazole can improve after successful treatment of hepatitis C.
A novel strategy for tumour therapy combining cell apoptosis and active immunity induced by caspy2, a zebrafish caspase

Caspy2, a zebrafish protease, is an active caspase for inducing apoptosis in mammalian cells. To investigate whether caspy2‐mediated apoptosis could be used in cancer therapy, its cDNA was amplified and cloned into eukaryotic expression vector pcDNA3.1+. The recombinant plasmid was mixed with cationic liposome and introduced into various tumour cell lines in vitro. Our data showed that caspy2 induced remarkable apoptosis of cancer cells in vitro. Treatment of mice‐bearing CT26 colon carcinoma or MethA fibrosarcoma with intratumoral injection of liposome‐caspy2 plasmid complex resulted in substantial killing of neoplastic cells and long‐term survivors. Apoptotic cells were widely distributed in caspy2‐treated tumour tissue. Infiltration of CD8+ T lymphocyte was also observed apparently in the tumour tissue after the treatment with caspy2. Tumour‐specific major histocompatibility complex (MHC) class I‐dependent CD8+ cytotoxic T lymphocyte activity was found by means of 51Cr release assay. In MethA model, the mice acquired a long‐time protective immunity against the parental tumour cell re‐challenge. These results indicated that caspy2 can act as both apoptosis inducer and immune response initiator, which may account for its extraordinary antitumour effect. Furthermore, in vivo depletion of CD8+ T lymphocytes could completely abrogate the antitumour immune activity, whereas the depletion of CD4+ cells showed partial abrogation. In this study, we developed a novel anticancer strategy that combines both induction of apoptosis and immune response in mice‐bearing tumours with a single caspy2 gene. This approach may provide an important way for treatment of cancer.
College Students' Smoking Behavior, Perceived Stress, and Coping Styles

The purpose of this study was to examine college students' smoking behavior as well as their current smoking status and its effects on perceived levels of stress and coping styles. Students from four universities completed the Perceived Stress Scale, the Coping Inventory for Stressful Situations and a smoking questionnaire. Of the 1330 students who participated in the study, 19 percent were current smokers. On the Perceived Stress Scale, current smokers' mean score was significantly higher than that of the students who had never smoked. In addition, the current smokers' mean score for Emotion-oriented Coping was significantly higher than that of the students who had never smoked or formerly smoked. The former smokers' mean score on Avoidance-oriented Coping was significantly lower than the never and the current smokers. Ten percent of the students smoked their first cigarette after high school, while 11 percent started to smoke on a daily basis after high school. Based on the findings, programs that focus on smoking prevention and cessation for college students are recommended.
Demo Abstract: How Fuzzy Logic can enhance Energy Management in autonomous Wireless Sensor Nodes ?

Power management is an important issue in the design of Energy Harvesting Wireless Sensor Networks (EH-WSNs). In this kind of networks, each Energy Harvesting Node (EH-node) must dynamically adapt its performance in order to avoid power failures while maintaining a good quality of service. The power management policy is implemented on each node by a Power Manager (PM). In this demonstration, the behaviour of Fuzzyman, a novel PM based on fuzzy control, is introduced. The performance of this PM is also shown in terms of energy budget and throughput for a given protocol. Moreover, the benefit of using emerging wake-up radio technology is also demonstrated.
On the choice of tactile code

Tactile codes and devices are widely used in virtual reality, robotics, and telemanipulation by blind and sighted people. Based upon the Braille code, we provide a rigorous analysis of tactile spatial codes, and propose a code that is improved in the information theoretical sense. Based upon the criterion of a minimum average code word weight, we derive a code that provides improved reliability and longer lifetime of tactile devices. Such an approach can be also employed for robot hands, and tactile feedback in virtual reality and dextrous telemanipulation.
An Empirical Comparison of Fast and Slow Stochastics

This paper compares the profitability of Stochastic Oscillators (STC) in 13 major stock market indices worldwide. We demonstrate, in contrast to common expectations, that the fast STC outperforms the slow STC in most markets, despite that fact that the latter can filter noisy trading signals whilst the prior cannot.
COEVOLUTION OF MUTUALISM BETWEEN ANTS AND ACACIAS IN CENTRAL AMERICA

The purpose of this paper is to discuss the coevolution of one of the more thoroughly studied mutualistic systems in the New World tropics: the interdependency between the swollen-thorn acacias and their ant inhabitants. This system has recently been described in detail in respect to one species of plant, Acacia cornigera L. (Mimosoideae; Leguminosae), and one species of ant, Pseudomyrmex ferruginea F. Smith (Pseudomyrmecinae; Formicidae), and shown experimentally to be a case of mutualism (Janzen, 1966a). In this species pair, the ant is dependent upon the acacia for food and domicile, and the acacia is dependent upon the ant for protection from phytophagous insects and neighboring plants. The literature dealing only with the New World tropical acacias (Acacia spp.) and their ants (Pseudomyrmex spp.) has been re-evaluated by Janzen (1966a) and will not be discussed further in a review sense. The higher plants that commonly have ant colonies living in them have long been termed myrmecophytes. Ants living in plants range in habit from fortuitous usage of a plant cavity to highly complex interaction systems between the ant and the higher plant. The ant-acacia system represents this latter extreme, and the acacia is by any definition a myrmecophyte. A review paper on the subject of myrmecophytes is in preparation. In the present paper, plants with ants living in them will be called "ant-plants"; the ants will be called "plant-ants. " The "swollen-thorn acacias" are those with 1) enlarged stipular thorns normally tenanted by ants, 2) enlarged foliar nectaries, 3) modified leaflet tips called Beltian bodies (eaten by the ants), and 4) nearly year-round leaf production and maintenance even in areas with a distinct dry season (Fig. 1). Swollen-thorn acacias have been shown experimentally to have a virtually obligate dependency on 1 Contribution No. 1308 from the Department of Entomology, The University of Kansas, Lawrence. This study was supported by National Science Foundation Grant GB-1428 to the University of California, Berkeley (Dr. R. F. Smith), University of California Associates in Tropical Biogeography Research Grants 66 and 81, and The University of Kansas General Research Grant 3173-5038, and also is a by-product of National Science Foundation Grant GB-91 (Dr. C. D. Michener).
Mitochondrial function/dysfunction in white adipose tissue

What is the topic of this review? The review covers basic knowledge about the role of mitochondria in the homeostatic function of adipose tissue. It also provide a comprehensive analysis of how mitochondrial function is affected during obesity and lipoatrophies and discuss the results of recent studies that targeted mitochondrial function specifically in adipose tissue or in fat cells and how these interventions affected whole body adiposity and peripheral insulin sensitivity. What advances does it highlight? The review provides specific highlights of the major roles of mitochondria in key metabolic processes that occur in adipose tissue including its role in adipogenesis, adipokine secretion, lipogenesis, fatty acid esterification, branched‐chain amino acid catabolism and lipolysis. Furthermore, we provide the reader with an update on the specific defects that affect mitochondrial function in adipose tissue during obesity and lipoatrophies. Finally, we discuss the latest mouse studies that specifically targeted mitochondrial function in adipose tissue to assess its contribution to the pathogenesis of obesity and insulin resistance.
Fuzzy pricing of American options on stocks with known dividends and its algorithm

The path‐dependent property of American options leads to the complexity of its pricing. Based on the analysis of American options' characteristics and the influence of the stock dividend, the American call option fuzzy pricing method is discussed in this paper. Under the assumption that the price of stock, discount rate, the volatility, and interest rate are all fuzzy numbers, the fuzzy pricing formula of American option is proposed by using the Black–Scholes pricing model. Then the interpolation search algorithm is designed to solve the proposed pricing model. Finally, the validity and accuracy of this model and its algorithm have to be tested with some numerical examples. © 2010 Wiley Periodicals, Inc.
Effect of coenzyme Q₁₀ supplementation on heart failure: a meta-analysis.

BACKGROUND Coenzyme Q₁₀ (CoQ₁₀; also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of CoQ₁₀ on CHF with inconclusive results. OBJECTIVE The objective of this meta-analysis was to evaluate the impact of CoQ₁₀ supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF. DESIGN A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ₁₀ supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol. RESULTS Supplementation with CoQ₁₀ resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and -0.30 (95% CI: -0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ₁₀/d and in patients with less severe CHF. These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup. CONCLUSIONS Pooled analyses of available randomized controlled trials suggest that CoQ₁₀ may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed.
The rpoE gene encoding the sigma E (sigma 24) heat shock sigma factor of Escherichia coli.

Previous work has established that the transcription factor sigma E (sigma 24) is necessary for maintaining the induction of the heat shock response of Escherichia coli at high temperatures. We have identified the gene encoding sigma E using a genetic screen designed to isolate trans‐acting mutations that abolish expression from either htrA or rpoHP3, two promoters recognized uniquely by sigma E‐containing RNA polymerase. Such a screen was achieved by transducing strains carrying a single copy of either phtrA‐lacZ or rpoHP3‐lacZ fusions with mutagenized bacteriophage P1 lysates and screening for Lac‐ mutant colonies at 22 degrees C. Lac‐ mutants were subsequently tested for inability to grow at 43 degrees C (Ts‐ phenotype). Only those Lac‐ Ts‐ mutants that were unable to accumulate heat shock proteins at 50 degrees C were retained for further characterization. In a complementary approach, those genes which when cloned on a multicopy plasmid led to higher constitutive expression of the sigma E regulon were characterized and mapped. Both approaches identified the same gene, rpoE, mapping at 55.5 min on the E.coli genetic map and encoding a polypeptide of 191 amino acid residues. The wild‐type and a mutant rpoE gene products were over‐expressed and purified. It was found that the purified wild‐type sigma E protein, when used in in vitro run‐off transcription assays in combination with core RNA polymerase, was able to direct transcription from the htrA and rpoHP3 promoters, but not from known sigma 70‐dependent promoters. In vivo and in vitro analyses of rpoE transcriptional regulation showed that the rpoE gene is transcribed from two major promoters, one of which is positively regulated by sigma E itself.