Miracle-dz/UniFAR-FTUs huggingface dataset:
Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock

ABSTRACT Objective: Hemorrhagic shock may contribute to acute kidney injury (AKI) by profoundly altering renal mitochondrial function. Resveratrol (RSV), a naturally occurring sirtuin 1 (SIRT1) activator, has been shown to promote mitochondrial function and reduce oxidative damage in a variety of aging-related disease states. We hypothesized that RSV treatment during resuscitation would ameliorate kidney mitochondrial dysfunction and decrease oxidative damage following hemorrhagic shock. Methods: Using a decompensated hemorrhagic shock model, male Long-Evans rats (n = 6 per group) were killed prior to hemorrhage (sham), at severe shock, and following either lactated Ringer’s (LR) resuscitation or LR + RSV resuscitation (RSV: 30 mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood urea nitrogen, and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (complexes I, II, and IV) using high-resolution respirometry. Total mitochondria reactive oxygen species were measured using fluorometry, and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. Quantitative polymerase chain reaction was used quantify mRNA from peroxisome proliferator–activated receptor &ggr; coactivator 1-&agr; (PGC1-&agr;) SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis. Results: Resveratrol supplementation during resuscitation restored mitochondrial respiratory capacity and decreased mitochondrial reactive oxygen species and lipid peroxidation. Compared with standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-&agr; expression and significantly increased both superoxide dismutase 2 and catalase expression. Although RSV was associated with decreased lactate production, pH, blood urea nitrogen, and serum creatinine values did not differ between resuscitation strategies. Conclusions: Resuscitation with RSV significantly restored renal mitochondrial function and decreased oxidative damage following hemorrhagic shock.
Application of a novel regulatable Cre recombinase system to define the role of liver and gut metabolism in drug oral bioavailability

The relative contribution of hepatic compared with intestinal oxidative metabolism is a crucial factor in drug oral bioavailability and therapeutic efficacy. Oxidative metabolism is mediated by the cytochrome P450 mono-oxygenase system to which cytochrome P450 reductase (POR) is the essential electron donor. In order to study the relative importance of these pathways in drug disposition, we have generated a novel mouse line where Cre recombinase is driven off the endogenous Cyp1a1 gene promoter; this line was then crossed on to a floxed POR mouse. A 40 mg/kg dose of the Cyp1a1 inducer 3-methylcholanthrene (3MC) eliminated POR expression in both liver and small intestine, whereas treatment at 4 mg/kg led to a more targeted deletion in the liver. Using this approach, we have studied the pharmacokinetics of three probe drugs – paroxetine, midazolam, nelfinavir – and show that intestinal metabolism is a determinant of oral bioavailability for the two latter compounds. The Endogenous Reductase Locus (ERL) mouse represents a significant advance on previous POR deletion models as it allows direct comparison of hepatic and intestinal effects on drug and xenobiotic clearance using lower doses of a single Cre inducing agent, and in addition minimizes any cytotoxic effects, which may compromise interpretation of the experimental data.
Polymorphisms of UDP-Glucuronosyltransferase and Pharmacokinetics of Irinotecan

Irinotecan is a prodrug that is hydrolyzed by carboxylesterase in vivo to form an active metabolite SN-38. SN-38 is further conjugated and detoxified by UDP-glucuronosyltransferase (UGT) to yield its β-glucuronide (SN-38G). Although irinotecan is widely used, the drug causes unpredictably severe, occasionally fatal, toxicity of leukopenia or diarrhea. Interindividual variation of sensitivity to irinotecan is related to large variations of biotransformation of the active metabolite SN-38, some of which would be caused by genetic polymorphism of UGT1A1, an isozyme responsible for the SN-38 glucuronidation. As a surrogate for the UGT activity, the polymorphic frequency distribution of the area under the concentration–time curve (AUC) ratios of SN-38 to SN-38G (AUCSN-38/AUCSN-38G) using pooled pharmacokinetic data from four independent study groups in Japan was explored. The data from 100 cancer patients was analyzed, including 14 who were genotyped for UGT1A1 gene in the previous studies. The median ratios of AUCSN-38/AUCSN-38G was 0.40 (interquartile range, 0.30 to 0.55; range, 0.09 to 2.32). Frequency distribution of the AUCSN-38/AUCSN-38G was skewed to the right without bimodality and the patient population could not be segregated into discrete subgroups that differ in the UGT activity by the AUC ratios. The 4 subjects carrying UGT1A1*28 allele had values of the AUCSN-38/AUCSN-38G above the 75th percentile of the total population, suggesting a potential pharmacogenetic/pharmacokinetic relationship. Ordinary values with a median of 0.41 (interquartile range, 0.33 to 0.49) were obtained for the UGT1A1*6 heterozygous patient and the 9 UGT1A1*1 homozygous patients (the reference sequence). The large variation in the UGT activity being related to the genetic status would warrant pharmacogenetic-guided dosing of irinotecan.
Applications for Bacteriophage Therapy during Pregnancy and the Perinatal Period

Pregnant women and their unborn children are a population that is particularly vulnerable to bacterial infection. Physiological changes that occur during pregnancy affect the way women respond to such infections and the options that clinicians have for treatment. Antibiotics are still considered the best option for active infections and a suitable prophylaxis for prevention of potential infections, such as vaginal/rectal Streptococcus agalactiae colonization prior to birth. The effect of such antibiotic use on the developing fetus, however, is still largely unknown. Recent research has suggested that the fetal gut microbiota plays a critical role in fetal immunologic programming. Hence, even minor alterations in this microbiota may have potentially significant downstream effects. An ideal antibacterial therapeutic for administration during pregnancy would be one that is highly specific for its target, leaving the surrounding microbiota intact. This review first provides a basic overview of the challenges a clinician faces when administering therapeutics to a pregnant patient and then goes on to explore common bacterial infections in pregnancy, use of antibiotics for treatment/prevention of such infections and the consequences of such treatment for the mother and infant. With this background established, the review then explores the potential for use of bacteriophage (phage) therapy as an alternative to antibiotics during the antenatal period. Many previous reviews have highlighted the revitalization of and potential for phage therapy for treatment of a range of bacterial infections, particularly in the context of the increasing threat of widespread antibiotic resistance. However, information on the potential for the use of phage therapeutics in pregnancy is lacking. This review aims to provide a thorough overview of studies of this nature and discuss the feasibility of bacteriophage use during pregnancy to treat and/or prevent bacterial infections.
Chemiluminescence spectra of human myeloperoxidase and polymorphonuclear leukocytes

The light emission spectra of myeloperoxidase-H2O2-Cl- and phagocytizing polymorphonuclear leukocytes were estimated by a computer simulation technique by using light transmittance data from nine band-pass filters. No shift in the chemiluminescence spectrum of either system was observed during the course of the reactions, suggesting that the light-generating mechanisms remain constant after their initiation. Transmittances were virtually identical for both myeloperoxidase-H2-O2-Cl- and polymorphonuclear leukocyte reactions, suggesting that the light-generating mechanisms are identical and leading to the estimation of nearly identical spectra. Both spectra were broad, with maximum light emission near 570 nm.
Learning Ordered Word Representations

*Correspondence: wxx@cslt.riit. tsinghua.edu. cn Center for Speech and Language Technology, Research Institute of Information Technology, Tsinghua University, ROOM 1-303, BLDG FIT, 100084 Beijing, China Full list of author information is available at the end of the article Abstract Learning distributed word representations, or word embeddings, has gained much popularity. Current learning approaches treat all dimensions of the embeddings as homogeneous, which leads to non-structured representations where the dimensions are neither interpretable nor comparable. This paper presents ordered word embeddings where the significance of the dimensions is in descending order. The order in dimensions may benefit a wide range of applications such as fast search and vector tailor. Three algorithms are proposed to learn the ordered embeddings, based on dropout, learning rate decay and sparse penalties, respectively. Additionally, a sweeping approach based on the χ distribution is proposed to ensure sufficient training for all dimensions. The experimental results on the WordSimilarity-353 task confirmed that the proposed methods indeed produce ordered embeddings, and better performance can be achieved with ordered representations when compared to the non-ordered counterparts.
The Role of Family Communication in Individual Health Attitudes and Behaviors Concerning Diet and Physical Activity

This study explored associations among family communication patterns (conversation and conformity orientations), health-specific communication variables, health attitudes, and health behaviors in a sample of 433 family dyads (N = 866). As expected, results of multilevel models revealed that individuals’ health attitudes were strongly associated with their self-reported health behaviors. Findings also suggested that perceived confirmation from a family member during health-specific conversations (a) directly influenced health attitudes, (b) partially accounted for the positive relationship between family conversation orientation and health attitudes, and (c) partially accounted for the inverse relationship between family conformity orientation and health attitudes. Similarly, frequency of health-specific communication (a) directly influenced health attitudes, (b) partially accounted for the positive relationship between family conversation orientation and health attitudes, and (c) directly associated with health behaviors. Results from an actor-partner interdependence model (APIM) supported the aforementioned within-person association between a person's own health attitudes and health behaviors, as well as a positive relationship between young adults’ health attitudes and their influential family member's health behaviors. Implications of these findings are discussed as they relate to theory and obesity prevention.
Prevalence and Correlates of Fatigue in Chronic Kidney Disease and End-Stage Renal Disease: Are Sleep Disorders a Key to Understanding Fatigue?

Background: Fatigue is an important symptom to patients with advanced chronic kidney disease (CKD). The aim of this study is to examine the prevalence and severity of fatigue among non-dialysis-dependent CKD and end-stage renal disease (ESRD) patients, to examine the association of fatigue with subjective and objective sleep quality, and to identify other modifiable factors associated with fatigue. Methods: A cross-sectional survey of 87 non-dialysis-dependent CKD (eGFR ≤45 ml/min/1.73 m2) and 86 ESRD patients was done using the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) and 36-Item Short-Form (SF-36) vitality scale. Higher FACIT-F score denoted less fatigue. Objective sleep was assessed using in-home polysomnography. Predictors of fatigue were determined using a linear regression model. Results: The mean FACIT-F score among all participants was 34.5 ± 11.0. Mean scores were similar among CKD and ESRD groups (34.25 ± 11.28 vs. 34.73 ± 10.86; p = 0.73). On univariate analyses, patients with higher levels of fatigue were more likely to have cardiovascular disease, benzodiazepine use, depressive symptoms, and slightly lower hemoglobin and serum albumin levels. There was no significant association between severity of sleep apnea and level of fatigue (Apnea Hypopnea Index 20.1 ± 27.6 vs. 20.3 ± 22.0; p = 0.69). Presence of cardiovascular disease, low serum albumin, depressive symptoms, poor subjective sleep quality, excessive daytime sleepiness and restless legs syndrome were independently associated with greater fatigue in multivariable regression models. The FACIT-F score correlated closely with the SF-36 vitality score (r = 0.81, p < 0.0001). Conclusions: Patients with advanced CKD and ESRD experience profound fatigue. Depressive symptoms, restless legs syndrome, excessive daytime sleepiness, and low albumin levels may provide targets for interventions to improve fatigue in patients with advanced CKD.
Gaussian mixture filtering for data fusion with switching observation models: Application to aircraft relative altimetry

The relative altitude sensing function onboard aircraft is currently supported by the radio-altimeters system along with specific thresholding and voting logics. In order to improve its accuracy and integrity a multi-sensor data fusion is proposed that may involve radio altimeters, GPS information, terrain database, barometer, lidar and inertial measurements. Because these sensors are likely to be affected by multiple malfunctions we are faced to a linear state estimation problem with switching observation models.
Der lange Weg der Konvergenz

Nach fast 20 Jahren wirtschaftlicher Entwicklung im vereinten Deutschland ist der Ruckstand der Neuen Bundeslander noch immer betrachtlich. Zwar wuchs die Wirtschaft nach der Vereinigungskrise in der ersten Halfte der 90er Jahre – ausgehend von einem niedrigen Niveau – kraftig, danach ging der Wachstumsvorsprung jedoch weitgehend verloren. Vor diesem Hintergrund stellt sich die Frage, wie der weitere Aufholprozess Ostdeutschlands zukunftig gestaltet sein wird. Ist zu erwarten, dass Ostdeutschland bezuglich des Wohlstandsniveaus zugig aufschliesen wird, oder ist Ostdeutschland endgultig abgehangt und wird niemals das westdeutsche Niveau erreichen? Diese Fragestellung wird im Rahmen einer Konvergenzanalyse auf Ebene der Bundeslander und im direkten Ost-West-Vergleich anhand der Pro-Kopf-Produktion empirisch untersucht. Auf Bundeslanderebene kann fur die Jahre 1995 bis 2008 eine durchschnittliche Konvergenzgeschwindigkeit von ungefahr 2% nachgewiesen werden. Demographische Effekte und die Migration von Ost nach West sind dabei wichtige Faktoren. In der aggregierten Betrachtung erscheint der Aufholprozess Ostdeutschlands noch schleppender zu verlaufen. Die Aufholgeschwindigkeit betragt dabei ungefahr 1% jahrlich. Die Resultate der hier verwendeten empirischen Untersuchungen geben wenig Anlass zu Optimismus im Hinblick auf die baldige Angleichung der Pro-Kopf-Produktion zwischen Ost- und Westdeutschland. Insgesamt spricht die Datenlage zwar fur die Konvergenz Ostdeutschlands relativ zum westdeutschen Wohlstandsniveau. Allerdings verlauft dieser Prozess sehr langsam – eine vollstandige Angleichung kann somit erst in einigen Jahr-zehnten erwartet werden.
Integration of information systems – a case study

In an increasingly competitive and globalised market, managing the flow of information in a company in an efficient manner is vital. The purpose of the current case study in a pharmaceutical company is to see how the information systems could be integrated and the IT system support for business processes improved to provide an enterprise architecture that facilitates the access to and improves the quality of information. A service oriented perspective has been used to investigate the application usage in business processes of both manufacturing and supporting flows, and based on these, possible changes to data storage, addition of new functionality and interfaces between systems are suggested. Synchronising data between systems and storing and accessing data in another system could be achieved using services in combination with a publish-subscribe mechanism, where publishing systems can inform interested parties of events that occur to allow them to take relevant action. A list of possible web services to be part of a Service-Oriented Architecture (SOA) is presented together with a list of events and the systems generating or potentially taking an interest in them. Collecting and organising data from several systems for trending, statistics and business decision support could be performed by regular batch transfers of data to a data warehouse. Authentication and encryption should be used to ensure data integrity and confidentiality for all information in transit. Using loosely coupled web services to share information allows separating concepts, e.g. “employee” or “product” from the way information about them is stored, and clients of a service do not need to know what happens internally in the service. This allows making changes to underlying systems without affecting the rest of the IT landscape. Services can also be re-used in e.g. interfaces to several other systems or to present data to a user in an application, a web site or a mobile phone, adding both flexibility and cost-effectiveness. Integration av informationssystem – en fallstudie
Functional characterization of thermolabile DNA-binding proteins that affect adenovirus DNA replication

The human adenovirus type 2 (Ad2) mutant Ad2ts111 has previously been shown to contain two mutations which result in a complex phenotype. Ad2ts111 contains a single base change in the early region 1B (E1B) 19,000-molecular-weight (19K) coding region which yields a cyt deg phenotype and another defect which maps to the E2A 72K DNA-binding protein (DBP) coding region that causes a temperature-sensitive DNA replication phenotype. Here we report that the defect in the Ad2ts111 DBP is due to a single G----T transversion that results in a substitution of valine for glycine at amino acid 280. A temperature-independent revertant, Ad2ts111R10, was isolated, which reverts back to glycine at amino acid 280 yet retains the cyt and deg phenotypes caused by the 19K mutation. We physically separated the two mutations of Ad2ts111 by constructing a recombinant virus, Ad2ts111A, which contained a wild-type Ad2 E1B 19K gene and the gly----val mutation in the 72K gene. Ad2ts111A was cyt+ deg+, yet it was still defective for DNA replication at the nonpermissive temperature. The Ad2ts111 DBP mutation is located only two amino acids away from the site of the mutation in Ad2+ND1ts23, a previously sequenced DBP mutant. Biochemical studies of purified Ad2+ND1ts23 DBP showed that this protein was defective for elongation but not initiation of replication in a cell-free replication system consisting of purified Ad polymerase, terminal protein precursor, and nuclear factor I. Ad2+ND1ts23 DBP bound less tightly to single-strand DNA than did Ad2 DBP, as shown by salt gradient elution of purified DBPs from denatured DNA cellulose columns. This decreased binding to DNA was probably due to local conformational changes in the protein at a site that is critical for DNA binding rather than to global changes in protein structure, since both the Ad2+ND1ts23 and Ad2 DBPs showed identical cleavage patterns by the protease thermolysin at various temperatures.
Mcp 5 , a meiotic cell cortex protein , is required for nuclear movement mediated by dynein and microtubules in fi ssion yeast

The formation of heritable haploid gametes from diploid parental cells requires meiosis, a special type of cell division. After premeiotic DNA replication, homologous chromosome pairing and genetic recombination occur during prophase I with formation of bouquet arrangement conserved among species (for review see Harper et al., 2004). During prophase I of fi ssion yeast, horsetail nuclear movement occurs. It starts when all the telomeres become bundled at the spindle pole body (SPB; Hiraoka, 1998). Subsequently, the nucleus undergoes a dynamic oscilla tion, resulting in elongated nuclear morphology (Chikashige et al., 1994). This event has been proposed to facilitate the pairing of homologous chromosomes because it aligns the chromosomes in the same direction (through the bundling of their telomeric ends) and then shuffl es them around each other (Chikashige et al., 1994; Kohli, 1994; Niwa et al., 2000; Ding et al., 2004). It has been proposed that horsetail nuclear movement is predominantly due to the pulling of astral microtubules that link the SPB to cortical microtubule-attachment sites at the opposite end of the cell; the pulling force is believed to be provided by cytoplasmic dynein (Ding et al., 1998; Yamamoto et al., 1999; Yamamoto and Hiraoka, 2003) and the dynactin (Yamashita et al., 1997; Niccoli et al., 2004) complex. However, the details of these mechanisms are still almost completely unknown. A key to understanding nuclear oscillation is the identifi cation and characterization of the anchor protein at the cell cortex that binds to dynein. We report that a novel meiosis-specifi c gene named mcp5 (from meiotic coiled-coil protein) encodes a protein, Mcp5 (Saito et al., 2005), that functions as this anchor during the meiosis of Schizosaccharomyces pombe. Recently, we found that it is also registered as Mug21 (Martin-Castellanos et al., 2005). Mcp5/Mug21 is homologous to Num1 (nuclear migration) of Saccharomyces cerevisiae, ApsA (anucleate primary sterigmata) of Aspergillus nidurans, and Ami1 (anucleate microconnidia) of Podospra anserina, but these Num1-like proteins function during vegetative growth rather than in meiosis (Kormanec et al., 1991; Fischer and Timberlake, 1995; Graïa et al., 2000; Heil-Chapdelaine et al., 2000), unlike Mcp5. We demonstrate a contribution for such an anchoring mechanism in the process of homologue pairing during meiosis and establish a link between meiotic and mitotic nuclear behavior, albeit in different organisms.
Rate control on correlation coefficient of network delay

The demand to access multimedia data such as live video is increasing due to the spread of broadband access network. However, the Internet only provides so called best-effort service. The network condition of the Internet shows fluctuation. Delivering video without any control causes degradation of the final video quality. In this paper we propose a stream-rate control algorithm RC/sup 3/ that uses correlation of network delay to evaluate available bandwidth. We show performance of RC/sup 3/ derived from simulations.
Metabolic characteristics of 13‐cis‐retinoic acid (isotretinoin) and anti‐tumour activity of the 13‐cis‐retinoic acid metabolite 4‐oxo‐13‐cis‐retinoic acid in neuroblastoma

Isotretinoin (13‐cis‐retinoic acid; 13‐cRA) is a differentiation inducer used to treat minimal residual disease after myeloablative therapy for high‐risk neuroblastoma. However, more than 40% of children develop recurrent disease during or after 13‐cRA treatment. The plasma concentrations of 13‐cRA in earlier studies were considered subtherapeutic while 4‐oxo‐13‐cis‐RA (4‐oxo‐13‐cRA), a metabolite of 13‐cRA considered by some investigators as inactive, were greater than threefold higher than 13‐cRA. We sought to define the metabolic pathways of 13‐cRA and investigated the anti‐tumour activity of its major metabolite, 4‐oxo‐13‐cRA.