Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Variation in Aldo-Keto Reductase 1D1 (AKR1D1) Affects the Expression and Activity of Multiple Cytochrome P450s

Human liver gene regulatory (Bayesian) network analysis was previously used to identify a cytochrome P450 (P450) gene subnetwork with Aldo-keto reductase 1D1 (AKR1D1) as a key regulatory driver of this subnetwork. This study assessed the biologic importance of AKR1D1 [a key enzyme in the synthesis of bile acids, ligand activators of farnesoid X receptor (FXR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR), known transcriptional regulators of P450s] to hepatic P450 expression. Overexpression of AKR1D1 in primary human hepatocytes led to increased expression of CYP3A4, CYP2C8, CYP2C9, CYP2C19, and CYP2B6. Conversely, AKR1D1 knockdown decreased expression of these P450s. We resequenced AKR1D1 from 98 donor livers and identified a 3′-untranslated region (UTR) (rs1872930) single nucleotide polymorphism (SNP) significantly associated with higher AKR1D1 mRNA expression. AKR1D1 3′-UTR-luciferase reporter studies showed that the variant allele resulted in higher luciferase activity, suggesting that the SNP increases AKR1D1 mRNA stability and/or translation efficiency. Consistent with AKR1D1’s putative role as a driver of the P450 subnetwork, the AKR1D1 3′-UTR SNP was significantly associated with increased hepatic mRNA expression of multiple P450s (CYP3A4, CYP2C8, CYP2C9, CYP2C19, and CYP2B6) and CYP3A4, CYP2C8, CYP2C19, and CYP2B6 activities. After adjusting for multiple testing, the association remained significant for AKR1D1, CYP2C9, and CYP2C8 mRNA expression and CYP2C8 activity. These results provide new insights into the variation in expression and activity of P450s that can account for interindividual differences in drug metabolism/efficacy and adverse drug events. In conclusion, we provide the first experimental evidence supporting a role for AKR1D1 as a key genetic regulator of the P450 network.
Prolactin alters the mechanisms of B cell tolerance induction.

OBJECTIVE Autoimmune diseases predominantly affect women, suggesting that female sex hormones may play a role in the pathogenesis of such diseases. We have previously shown that persistent mild-to-moderate elevations in serum prolactin levels induce a break in self tolerance in mice with a BALB/c genetic background. The aim of this study was to evaluate the effects of hyperprolactinemia on the mechanisms of B cell tolerance induction. METHODS Effects of prolactin on splenic B cell subsets were studied in female BALB/c mice. B cell receptor (BCR)-mediated apoptosis and proliferation of transitional B cells were analyzed by flow cytometry. Expression of apoptotic genes was examined by microarrays and real-time polymerase chain reaction analysis. B cells coexpressing kappa/lambda light chains were assessed by flow cytometry and immunohistochemistry. Activation status of transitional type 3 (T3) B cells was evaluated by BCR-induced calcium influx studies. RESULTS BCR-mediated apoptosis of the T1 B cell subset, a major checkpoint for negative selection of autoreactive specificities, was decreased in prolactin-treated mice. Microarray studies indicated that this event may be mediated by the prolactin-induced up-regulation of the antiapoptotic gene interferon-gamma receptor type II and down-regulation of the proapoptotic gene Trp63. Prolactin treatment also altered the amount of receptor editing, as indicated by the increased number of transitional B cells coexpressing kappa/lambda light chains. Additionally, hyperprolactinemia modified the level of B cell anergy by increasing the degree of BCR-induced calcium influx in the T3 B cells. CONCLUSION Persistently elevated serum prolactin levels interfere with B cell tolerance induction by impairing BCR-mediated clonal deletion, deregulating receptor editing, and decreasing the threshold for activation of anergic B cells, thereby promoting autoreactivity.
Development of Brugia pahangi in the flight muscles of Aedes togoi. Ultrastructural changes in the infected muscle fibers and the infecting filarial larvae.

The ultrastructural changes seen in the indirect flight muscles of Aedes togoi infected with Brugia pahangi included the disarray or disruption of the parasitized muscle fiber, the reduction and disorganization of the interfibrillar mitochondria, the reduction of muscle glycogen and, finally, the complete dissolution of the muscle fiber. These changes are restricted to individual parasitized muscle fibers while adjacent non-parasitized fibers retain their usual arrangement. The damage inflicted to these parasitized fibers may be due to the presence and movement of the larvae within the fibrils and the active ingestion of muscle mitochondria by these developing larvae. The damaged muscle may be capable of partial repair as the extent of injury was usually less severe in infected mosquitoes from the 9th day after the infecting feed, when most of the infective larvae had migrated from the thorax to the head and proboscis.
Prospective Evaluation of Allograft Meniscus Transplantation

Background Clinical and biomechanical studies have demonstrated the increase in contact pressure and progressive deterioration of the tibiofemoral compartments that occur after partial or complete meniscectomy. Meniscus transplantation has been indicated for the symptomatic postmeniscectomy patient to alleviate symptoms and potentially prevent the progression of articular degeneration. Purpose To report the early-term results after allograft meniscus transplantations from a single institution performed by a single surgeon. Study Design Case series; Level of evidence, 4. Methods Forty-four meniscus transplants in 39 patients were evaluated at minimum 2-year follow-up using the Lysholm, Tegner, International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, Noyes symptom rating and sports activity, and SF-12 scoring systems; visual analog pain scales; patient satisfaction; and physical examination. Four transplants failed early, leaving 40 transplants in 36 patients for review. Patients were grouped into medial and lateral transplant groups as well as those with isolated and combined procedures. Twenty-one menisci were transplanted in isolation (52.5%), and 19 were combined with other procedures (47.5%) to address concomitant articular cartilage injury. Results Patients demonstrated statistically significant improvements in standardized outcomes surveys and visual analog pain and satisfaction scales. In 7 patients, treatment had failed at final follow-up. Overall, 77.5% of patients reported they were completely or mostly satisfied with the procedure, and 90% of patients were classified as normal or nearly normal using the International Knee Documentation Committee knee examination score at final follow-up. There were no significant differences in the medial and lateral subgroups, although the lateral subgroup did demonstrate a trend toward greater improvement. No significant differences were noted in the isolated and combined subgroups. Conclusion Meniscus transplantation alone or in combination with other reconstructive procedures results in reliable improvements in knee pain and function at minimum 2-year follow-up. Longer term studies are necessary to determine if transplantation can prevent the articular degeneration associated with meniscectomy.
Production of Biodiesel from Jatropha Oil (Jatropha curcas) in Pilot Plant

In this research, among the chemical properties, free fatty acid value of jatropha oil was determined to be 22.6%, 5.23% and 8.8% respectively. Total, free and combined glycerol percent of raw jatropha oil were 8.27 %, 0.58% and 7.69 % respectively. Yield of biodiesel from jatropha oil at optimal sodium hydroxide catalyst concentration 1%, reaction temperature 65°C, reaction time one hour and molar ratio of methanol to oil 6:1 was 92% from lab scale. Yield of biodiesel from jatropha oil at optimal potassium hydroxide catalyst concentration 1%, reaction temperature - room temperature, reaction time 5 hours and molar ratio of ethanol to oil 8:1 was 90% from the lab scale. Biodiesel was also produced from pilot plant at optimum transesterification process condition as stated above. The yield of biodiesel (methyl ester) and ethyl ester were 92% and 90% on the basis of refined jatropha oil in the pilot plant scale. The capacity of biodiesel pilot plant is 30 gal / day. The fuel properties of biodiesel, namely cetane index, flash point, pour point, kinematic viscosity, specific gravity, color, copper strip corrosion, acid value, water and sediment and distillation at 90% recovery, were found to be within the limits of American Society for Testing and Materials (ASTM) specifications for biodiesel and diesel fuel. The fuel consumption of the engine which used biodiesel produced from free fatty acid content 5.23% in raw jatropha oil is more than the fuel consumption of the engine which used biodiesel produced from free fatty acid content 1% in refined raw jatropha oil. Keywords—renewable energy, biodiesel, transesterification, methyl ester, ethyl ester, pilot plant.
The NO donor SIN‐1 improves intestinal–arterial Pco2 gap in experimental endotoxemia: an animal study

Background: Dysfunction of the microcirculation is a prominent feature of sepsis and endotoxemia. Recently, it has been shown that microcirculatory alterations are completely reversed by local or systemic application of vasodilators in severely septic patients. Therefore, we investigated the influence of vasodilator therapy on microcirculatory dysfunction of the ileum during endotoxic shock in a prospective, controlled animal study.
Fascin-1, Ezrin and Paxillin Contribute to the Malignant Progression and Are Predictors of Clinical Prognosis in Laryngeal Squamous Cell Carcinoma

Aims Fascin-1, ezrin and paxillin, cytoskeleton-associated proteins, have been implicated in several human cancers, but their role in laryngeal squamous cell carcinoma (LSCC) is unknown. We investigated the association of their expression and clinicopathologic factors and their prognostic value in LSCC. Materials and Methods Quantitative RT-PCR and western blot analyses were used to examine mRNA and protein levels in 10 fresh LSCC specimens and 10 corresponding adjacent normal margin (ANM) tissues from patients undergoing surgery in 2012. We used immunohistochemistry to retrospectively study 216 paraffin blocks of LSCC samples from patients (193 men) who had undergone surgery between 2000 and 2006 and had not received special treatment before the diagnosis. Univariate analysis of patient survival involved the Kaplan–Meier method. Multivariate analyses involved the Cox proportional hazards model. Results The relative mRNA and protein levels of fascin-1, ezrin and paxillin were significantly greater in LSCC than ANM tissue (P<0.05). The high expression of fascin-1, ezrin or paxillin was positively correlated with poor tumor differentiation, cervical lymph node metastasis (N+), and advanced clinical stage (III+IV) (P<0.05) but not sex or metastasis. In addition, a high expression of fascin-1 (P = 0.007) or ezrin (P = 0.047) was associated with advanced tumor stage (T3+T4). The expression of fascin-1 was higher in smokers than non-smokers (P = 0.019). A high expression of fascin-1, ezrin or paxillin was associated with poor prognosis. Conclusions Fascin-1, ezrin and paxillin may be prognostic of poor outcome with LSCC after surgery. Our study may lead to establishing new molecular therapeutic targets and/or prognostic biomarkers in LSCC.
Performance and resource modeling in highly-concurrent OLTP workloads

Database administrators of Online Transaction Processing (OLTP) systems constantly face difficult questions. For example, "What is the maximum throughput I can sustain with my current hardware? ", "How much disk I/O will my system perform if the requests per second double? ", or "What will happen if the ratio of transactions in my system changes? ". Resource prediction and performance analysis are both vital and difficult in this setting. Here the challenge is due to high degrees of concurrency, competition for resources, and complex interactions between transactions, all of which non-linearly impact performance. Although difficult, such analysis is a key component in enabling database administrators to understand which queries are eating up the resources, and how their system would scale under load. In this paper, we introduce our framework, called DBSeer, that addresses this problem by employing statistical models that provide resource and performance analysis and prediction for highly concurrent OLTP workloads. Our models are built on a small amount of training data from standard log information collected during normal system operation. These models are capable of accurately measuring several performance metrics, including resource consumption on a per-transaction-type basis, resource bottlenecks, and throughput at different load levels. We have validated these models on MySQL/Linux with numerous experiments on standard benchmarks (TPC-C) and real workloads (Wikipedia), observing high accuracy (within a few percent error) when predicting all of the above metrics.
Role of p12CDK2-AP1 in Transforming Growth Factor-β1-Mediated Growth Suppression

p12CDK2-AP1 (p12) is a growth suppressor isolated from normal keratinocytes. Ectopic expression of p12 in squamous carcinoma cells reversed the malignant phenotype of these cells, in part due an ability of p12 to bind to both DNA polymerase α/primase and to cyclin-dependent kinase 2 (CDK2), thereby inhibiting their activities. We report in this article that in normal epithelial cells, transforming growth factor β1 (TGF-β1) induces p12 expression transcriptionally, which, in turn, mediates the growth inhibitory activity of TGF-β1. We created inducible p12 antisense HaCaT cell lines [ip12 (−) HaCaT] and showed that selective reduction of cellular p12 resulted in an increase in: (a) CDK2-associated kinase activity; (b) protein retinoblastoma (pRB) phosphorylation; and (c) [3H]thymidine incorporation, and partially reversed TGF-β1-mediated inhibition of CDK2 kinase activity, pRB phosphorylation, and cell proliferation. Furthermore, we generated p12-deficient mouse oral keratinocytes (MOKp12−/−) and compared their growth characteristics and response to TGF-β1 with that of wild-type mouse oral keratinocytes (MOKWT). Under normal culture conditions, the number of MOKp12−/− in S phase is 2-fold greater than that of MOKWT. Concomitantly, fewer cells are in G2 phase in MOKp12−/− than that in MOKWT. Moreover, response to TGF-β1-mediated growth suppression is compromised in MOKp12−/− cells. Mechanistic studies showed that MOKp12−/− have increased CDK2 activity and reduced sensitivity to inhibition by TGF-β1. Collectively our data suggest that p12 plays a role in TGF-β1-mediated growth suppression by modulating CDK2 activities and pRB phosphorylation.
Medication reconciliation: barriers and facilitators from the perspectives of resident physicians and pharmacists.

BACKGROUND Medication reconciliation can prevent medication errors and harm when patients transition between hospital and other care settings. Though a Joint Commission hospital Patient Safety Goal since 2006, organizations continue to have difficulty implementing the process. OBJECTIVE To determine factors that influence performance of medication reconciliation in a hospital setting with a computerized medication reconciliation tool. DESIGN Cognitive task analysis (CTA) and focus group interviews. SETTING Urban, academic, tertiary-care Veterans Affairs medical center. PARTICIPANTS Internal medicine house staff physicians (n = 23) and inpatient staff pharmacists (n = 12). MEASUREMENTS CTA participants verbalized their thoughts while they completed medication reconciliation with the computerized tool. Focus group participants described medication reconciliation's purpose and effectiveness, how they completed the task, and its barriers and facilitators. Interviews were recorded and analyzed using social science methods for analyzing qualitative data. RESULTS Participants agreed that a central goal of medication reconciliation is to prevent prescribing errors, but disagreed about whether it achieves this goal. Computerization facilitated the task, but participants said that computers and patients can be unreliable sources of information. Participants varied in how they sequenced components of the task. When time was limited, physicians considered other responsibilities higher priority. Both physicians and pharmacists expressed low self-efficacy, ie, low perceived capability to achieve the objectives of the process. CONCLUSION Key barriers to medication reconciliation are unreliable sources of medication information and tasks that compete for providers' time and attention that they consider higher priority. Addressing these barriers while increasing providers' self-efficacy might improve medication reconciliation and its outcomes.
Consensus in networked multi-agent systems via sampled control: Fixed topology case

In this paper, consensus problems of continuous-time networked multi-agent systems via sampled control are investigated. The sampled control protocols are induced from continuous-time linear consensus protocol by using periodic sampling technology and zero-order hold circuit. Two cases are considered: 1) networks without sampling delay; 2) networks with sampling delay. For each case, an algebraic-type necessary and sufficient condition is obtained under which consensus is achieved. Some numerical simulations are presented, which are consistent with our theoretical results.
Growth Factor Receptor–Bound Protein 2 Contributes to (Hem)Immunoreceptor Tyrosine-Based Activation Motif–Mediated Signaling in Platelets

Rationale: Platelets are anuclear cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity but may also cause pathological vessel occlusion. One major pathway of platelet activation is triggered by 2 receptors that signal through an (hem)immunoreceptor tyrosine-based activation motif (ITAM), the activating collagen receptor glycoprotein (GP) VI and the C-type lectin-like receptor 2 (CLEC-2). Growth factor receptor–bound protein 2 (Grb2) is a ubiquitously expressed adapter molecule involved in signaling processes of numerous receptors in different cell types, but its function in platelets and MKs is unknown. Objective: We tested the hypothesis that Grb2 is a crucial adapter protein in (hem)immunoreceptor tyrosine-based activation motif signaling in platelets. Methods and Results: Here, we show that genetic ablation of Grb2 in MKs and platelets did not interfere with MK differentiation or platelet production. However, Grb2-deficiency severely impaired glycoprotein VI–mediated platelet activation because of defective stabilization of the linker of activated T-cell (LAT) signalosome and activation of downstream signaling proteins that resulted in reduced adhesion, aggregation, and coagulant activity on collagen in vitro. Similarly, CLEC-2–mediated signaling was impaired in Grb2-deficient platelets, whereas the cells responded normally to stimulation of G protein–coupled receptors. In vivo, this selective (hem)immunoreceptor tyrosine-based activation motif signaling defect resulted in prolonged bleeding times but affected arterial thrombus formation only after concomitant treatment with acetylsalicylic acid, indicating that defective glycoprotein VI signaling in the absence of Grb2 can be compensated through thromboxane A2–induced G protein–coupled receptor signaling pathways. Conclusions: These results reveal an important contribution of Grb2 in (hem)immunoreceptor tyrosine-based activation motif signaling in platelets in hemostasis and thrombosis by stabilizing the LAT signalosome.
Identification of Novel and Differentially Expressed MicroRNAs of Dairy Goat Mammary Gland Tissues Using Solexa Sequencing and Bioinformatics

MicroRNAs are small, noncoding RNA molecules that regulate gene expression at the post-transcriptional level and play an important role in various biological processes. Although most microRNAs expression profiles studies have been performed in humans or rodents, relatively limited knowledge also exists in other mammalian species. The identification of the full repertoire of microRNAs expressed in the lactating mammary gland of Capra hircus would significantly increase our understanding of the physiology of lactating mammary glands. In this study, two libraries were constructed using the lactating mammary gland tissues of Laoshan dairy goats (Capra hircus) during peak and late lactation. Solexa high-throughput sequencing technique and bioinformatics were used to determine the abundance and differential expression of the microRNAs between peak and late lactation. As a result, 19,044,002 and 7,385,833 clean reads were obtained, respectively, and 1,113 conserved known microRNAs and 31 potential novel microRNA candidates were identified. A total of 697 conserved microRNAs were significantly differentially expressed with a P-value<0.01, 272 microRNAs were up-regulated and 425 microRNAs were down-regulated during peak lactation. The results were validated using real-time quantitative RT-PCR. 762,557 annotated mRNA transcripts were predicted as putative target gene candidates. The GO annotation and KEGG pathway analysis suggested that differentially expressed microRNAs were involved in mammary gland physiology, including signal transduction, and cell-cell and cell-extracellular communications. This study provided the first global of the microRNA in Capra hircus and expanded the repertoire of microRNAs. Our results have great significance and value for the elucidation of complex regulatory networks between microRNAs and mRNAs and for the study of mammary gland physiology and lactation.
Memory deficit produced by bilateral lesions in the hippocampal zone.

It has often been assumed that memory depends upon the total action of the brain rather than upon some specialized intracerebral neuron mechanism. There is recent evidence, however, in support of the view that the recording of experience is localizable in the same sense that sensory functions and speech functions are localizable. Obviously, none of these subdivisions is separable from the work of the brain as a whole. The following study shows that the capacity to record the daily current of conscious experience may be lost when there is bilateral destruction of a man's hippocampus and hippocampal gyrus. Functional paralysis of this recording mechanism does not, however, interfere with the patient's intellectual performance in other psychological tests not dependent on recent memory. Skills, language, and all those things which have already been learned are not lost. This inability to record new experience is not found in cases of strictly unilateral
Modeling on quicksand: dealing with the scarcity of ground truth in interdomain routing data

Researchers studying the interdomain routing system, its properties and new protocols, face many challenges in performing realistic evaluations and simulations. Modeling decisions with respect to AS-level topology, routing policies and traffic matrices are complicated by a scarcity of ground truth for each of these components. Moreover, scalability issues arise when attempting to simulate over large (although still incomplete) empirically-derived AS-level topologies. In this paper, we discuss our approach for analyzing the robustness of our results to incomplete empirical data. We do this by (1) developing fast simulation algorithms that enable us to (2) running multiple simulations with varied parameters that test the sensitivity of our research results.