Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel human cytochrome P450 gene (P450IIB): chromosomal localization and evidence for alternative splicing

We have isolated from a single human liver cDNA library two clones which are highly homologous (78% over the coding region) to the major phenobarbital-inducible P450 from rat (P450IIB1). This is the first direct demonstration of the presence of the P450IIB gene subfamily in humans. This subfamily is much less extensive than the rodent homologues, but does appear to contain at least two genes. Of the cDNA clones isolated one is apparently normally spliced, whereas the other lacks exon 8 and retains all or part of intron 5. Both clones contain transcribed Alu sequences. The human P450IIB gene has been located to chromosome 19q12----19q13.2 using a probe derived from intron 5, and is close to the CYP 2A locus encoding cytochrome P450IIA2. Restriction fragment length polymorphisms have been found with the enzymes BamHI and MspI which will enable linkage to be determined between these two loci.
Two-Stage Hedonic Price Model for Light-Duty Vehicles

Consumers’ marginal willingness to pay for a unit change of automotive fuel economy was estimated through development of a hedonic regression of new automobiles sales. The research combined national data on vehicle attributes with a unique data set that contains demographic information on all new vehicles registered in Maine in 2007. The research estimates the impact of demographic factors on consumer demands for fuel economy by generating a function for fuel economy demand in a second-stage hedonic model. Results show that consumers undervalue the long-run fuel savings of vehicle ownership, but they significantly value short-run fuel savings. Age and education are positively correlated with fuel economy demand, whereas income is statistically insignificant. Car consumers’ net benefits from an increase in fuel economy from 25 to 35 mpg are computed from the fuel economy demand curve and are approximately $2,232. Strengthening corporate average fuel economy standards is reasonable because consumers can receive significant net benefits from increasing fuel economy.
Levobupivacaine Versus Racemic Bupivacaine for Spinal Anesthesia

Levobupivacaine is the pure S(−)-enantiomer of racemic bupivacaine but is less toxic to the heart and central nervous system. Although it has recently been introduced for routine obstetric and nonobstetric epidural anesthesia, comparative clinical studies on its intrathecal administration are not available. We therefore performed this prospective randomized double-blinded study to evaluate the anesthetic potencies and hemodynamics of intrathecal levobupivacaine compared with racemic bupivacaine. Eighty patients undergoing elective hip replacement received either 3.5 mL levobupivacaine 0.5% isobaric or 3.5 mL bupivacaine 0.5% isobaric. Sensory blockade was verified with the pinprick test; motor blockade was documented by using a modified Bromage score. Hemodynamic variables (e.g., blood pressure, heart rate, pulse oximetry) were also recorded. Intergroup differences between levobupivacaine and bupivacaine were insignificant both with regard to the onset time and the duration of sensory and motor blockade (11 ± 6 versus 13 ± 8 min; 10 ± 7 versus 9 ± 7 min; 228 ± 77 versus 237 ± 88 min; 280 ± 84 versus 284 ± 80 min). Both groups showed slight reductions in heart rate and mean arterial pressure, but there was no intergroup difference in hemodynamics. We conclude that intrathecal levobupivacaine is equal in efficacy to, but less toxic than, racemic bupivacaine.
STAT3 and STAT5A are potential therapeutic targets in castration-resistant prostate cancer

Mechanisms of castration-resistant prostate cancer (CRPC) are not well understood, thus hindering rational-based drug design. Activation of STAT3/5A, key components of the JAK/STAT pathway, is implicated in aggressive PC, yet their clinical relevance in CRPC remains elusive. Here, we evaluated the possible role of STAT3/5A in CRPC using immunological, quantitative mRNA expression profiling, and pharmacological methods. We observed a strong nuclear immunoreactivity for STAT3 and STAT5A in 93% (n=14/15) and 80% (n=12/15) of CRPC cases, respectively, compared with benign prostatic hyperplasia (BPH). We demonstrated that PC cells express varying levels of STAT3 and STAT5A transcripts. In addition, we demonstrate that pimozide, a psychotropic drug and an indirect inhibitor of STAT5, attenuated PC cells growth, and induced apoptosis in a dose-dependent manner. Furthermore, our analysis of the PC public data revealed that the STAT3/5A genes were frequently amplified in metastatic CRPC. These findings suggest that STAT3/5A potentially serves as a predictive biomarker to evaluate the therapeutic efficacy of a cancer drug targeting the JAK/STAT pathway. Since the JAK/STAT and AR pathways are suggested to be functionally synergistic, inhibition of the JAK/STAT signaling alone or together with AR may lead to a novel treatment modality for patients with advanced PC.
Amendment history : Expression of Concern ( July 2019 ) Tandem CAR T cells targeting HER 2 and IL 13 R a 2 mitigate tumor antigen escape

In preclinical models of glioblastoma, antigen escape variants can lead to tumor recurrence after treatment with CAR T cells that are redirected to single tumor antigens. Given the heterogeneous expression of antigens on glioblastomas, we hypothesized that a bispecific CAR molecule would mitigate antigen escape and improve the antitumor activity of T cells. Here, we created a CAR that joins a HER2-binding scFv and an IL13Ra2-binding IL-13 mutein to make a tandem CAR exodomain (TanCAR) and a CD28.z endodomain. We determined that patient TanCAR T cells showed distinct binding to HER2 or IL13Ra2 and had the capability to lyse autologous glioblastoma. TanCAR T cells exhibited activation dynamics that were comparable to those of single CAR T cells upon encounter of HER2 or IL13Ra2. We observed that TanCARs engaged HER2 and IL13Ra2 simultaneously by inducing HER2-IL13Ra2 heterodimers, which promoted superadditive T cell activation when both antigens were encountered concurrently. TanCAR T cell activity was more sustained but not more exhaustible than that of T cells that coexpressed a HER2 CAR and an IL13Ra2 CAR, T cells with a unispecific CAR, or a pooled product. In a murine glioblastoma model, TanCAR T [. ] Research Article Oncology
Question-Answering with Grammatically-Interpretable Representations

We introduce an architecture, the Tensor Product RecurrentNetwork (TPRN). In our application of TPRN, internal representations—learned by end-to-end optimization in a deep neural network performing a textual question-answering(QA) task—can be interpreted using basic concepts from linguistic theory. No performance penalty need be paid for this increased interpretability: the proposed model performs comparably to a state-of-the-art system on the SQuAD QA task.The internal representation which is interpreted is a Tensor Product Representation: for each input word, the model selects a symbol to encode the word, and a role in which to place the symbol, and binds the two together. The selection is via soft attention. The overall interpretation is built from interpretations of the symbols, as recruited by the trained model, and interpretations of the roles as used by the model. We find support for our initial hypothesis that symbols can be interpreted as lexical-semantic word meanings, while roles can be interpreted as approximations of grammatical roles (or categories)such as subject, wh-word, determiner, etc. Fine-grained analysis reveals specific correspondences between the learned roles and parts of speech as assigned by a standard tagger(Toutanova et al. 2003), and finds several discrepancies in the model’s favor. In this sense, the model learns significant aspectsof grammar, after having been exposed solely to linguistically unannotated text, questions, and answers: no prior linguistic knowledge is given to the model. What is given is the means to build representations using symbols and roles, with an inductive bias favoring use of these in an approximately discrete manner.
Large-Area Gap Filling of Landsat Reflectance Time Series by Spectral-Angle-Mapper Based Spatio-Temporal Similarity (SAMSTS)

Landsat time series commonly contain missing observations, i.e., gaps, due to the orbit and sensing geometry, data acquisition strategy, and cloud contamination. A spectral-angle-mapper (SAM) based spatio-temporal similarity (SAMSTS) gap-filling algorithm is presented that is designed to fill small and large area gaps in Landsat data, using one year or less of data and without using other satellite data. Each gap pixel is filled by an alternative similar pixel that is located in a non-missing region of the image. The alternative similar pixel locations are identified by comparison of reflectance time series using a SAM metric revised to be adaptive to missing observations. A time series segmentation-and-clustering approach is used to increase the search efficiency. The SAMSTS algorithm is demonstrated using six months of Landsat 8 Operational Land Imager (OLI) reflectance time series over three 150 × 150 km (5000 × 5000 30 m pixels) areas in California, Minnesota and Kansas. The three areas contain different land cover types, especially crops that have different phenology and abrupt changes due to agricultural harvesting, which make gap filling challenging. Fillings on simulated gaps, which are equivalent to 36% of 5000 × 5000 images in each test area, are presented. The gap filling accuracy is assessed quantitatively, and the SAMSTS algorithm is shown to perform better than the simple closest temporal pixel substitution gap filling approach and the sinusoidal harmonic model-based gap filling approach. The SAMSTS algorithm provides gap-filled data with five-band reflective-wavelength root-mean-square differences less the 0.02, which is comparable to the OLI reflectance calibration accuracy.
Estimating Risk Premia in Money Market Rates

This paper empirically tests the expectations hypothesis on both daily EONIA swap rates and monthly EURIBOR rates extended backwards with German LIBOR rates. In addition, we quantify the size of the risk premia in the money market at maturities of one, three, six and nine months. Using implied forward and spot rates in a cointegrated VAR model, we find that the data support the expectations hypothesis in the euro area and in Germany prior to 1999. We find that risk premia are relatively limited at the shorter maturities but more significant at maturities of six and nine months. Furthermore, the results on LIBOR/EURIBOR rates tentatively indicate a downward shift in the structure of the risk premia after the introduction of the euro. JEL Classification: E43, C32
Wake up, Europe!

We live in a world of rapid transition. Yet while, in the United States, it is hard to escape discussions of the changing international system and its implications, such debates are largely absent in Europe. This is all the more serious in that Europe is both more vulnerable than the USA to the myriad new threats on the horizon and less well equipped to confront them. We outline the nature of the challenges confronting Europe, and suggest that the solution lies, first and foremost, in national capitals. Virtually all EU member states attach unwarranted importance to “sovereignty”, while fully aware that, alone, they count for nothing as foreign policy and security actors. It is only if the EU member states understand the nature of the threats they face and consent to tackle them collaboratively that Europe will be in a position to defend its interests effectively.
Oral food challenges: result of a 16-year experience at a major teaching hospital in Thailand

Background Prevalence of food allergy is increasing all over the world including in Asia. Diagnosis of food allergy in Asia is usually made after family complaints or by elimination and/or reintroduction foods. This could lead to an inaccurate diagnosis and to incorrect information on epidemiology of food allergy. We, herein, reported results of a 16-year experience (1996–2012) of oral food challenge (OFC) performed in pediatric patients at a major teaching hospital in Thailand. Objective The major objectives of this report are to review types of foods selected for oral challenges, frequency of positive/negative challenges to these foods and the clinical reactions during challenges among these children. Methods Medical records of 206 children underwent OFC between 1996 and 2012 for various indications at the Allergy clinic of Pediatric Department, Siriraj Hospital, Mahidol University (age range, 4 months to 17 years) were retrospectively reviewed. Data including clinical data, skin prick test results and specific IgE levels were analyzed with respect to challenge results (positive/negative). During the period of the study, 2 separate investigations on shrimp allergy and wheat allergy were conducted. Results Sixty of 206 children (29%) had positive OFC, whereas 84 out of 306 OFC (27.5%) were positive. The most common food giving positive challenges in this study was shrimp (40%). Among children less than 3 years of age, the most common food with positive challenge was wheat (70%) whereas among children 3 years of age or older, shellfish was the most common food (42%). Cutaneous reactions were the most common reactions observed. Conclusion Only 1 out of 3 children underwent OFC in this study had positive challenges. Shrimp was the most common food causing challenge in this study especially among children older than 3 years of age. Wheat has become another leading food besides cow's milk and egg in causing positive OFC in younger children in Thailand.
Resistance to a Novel Antichlamydial Compound Is Mediated through Mutations in Chlamydia trachomatis secY

ABSTRACT A novel and quantitative high-throughput screening approach was explored as a tool for the identification of novel compounds that inhibit chlamydial growth in mammalian cells. The assay is based on accumulation of a fluorescent marker by intracellular chlamydiae. Its utility was demonstrated by screening 42,000 chemically defined compounds against Chlamydia caviae GPIC. This analysis led to the identification of 40 primary-hit compounds. Five of these compounds were nontoxic to host cells and had similar activities against both C. caviae GPIC and Chlamydia trachomatis. The inhibitory activity of one of the compounds, (3-methoxyphenyl)-(4,4,7-trimethyl-4,5-dihydro-1H-[1,2]dithiolo[3,4-C]quinolin-1-ylidene)amine (MDQA), was chlamydia specific and was selected for further study. Selection for resistance to MDQA led to the generation of three independent resistant clones of C. trachomatis. Amino acid changes in SecY, a protein involved in Sec-dependent secretion in Gram-negative bacteria, were associated with the resistance phenotype. The amino acids changed in each of the resistant mutants are located in the predicted central channel of a SecY crystal structure, based on the known structure of Thermus thermophilus SecY. These experiments model a process that can be used for the discovery of antichlamydial, anti-intracellular, or antibacterial compounds and has led to the identification of compounds that may have utility in both antibiotic discovery and furthering our understanding of chlamydial biology.
Market position, resource profile, and governance: linking Porter and Williamson in the context of international courier and small package services in Japan

Two economic theories that have had an immense impact on modern strategic management research are Porter's strategic positioning framework (SPF) and Williamson's transaction cost economics (TCE). While both theories have contributed to our understanding of strategic management and to the choice of strategy and structure, each theory offers managerial prescriptions that are incomplete at best. We contend that if followed in isolation, each theory can lead to inferior performance. This paper, which studies the international courier and small package (ICS nevertheless, it provides one of the first attempts to theoretically and empirically link Porter's SPF and Williamson's TCE. Copyright © 2001 John Wiley & Sons, Ltd.
Performance-Based Pay in the Australian Public Service

This article explores employee responses to the performance-based pay schemes introduced into the Australian Public service in 1998 and 1999. Many federal public sector employees were aware ofthe subjectivity and enhanced mana gerial discretion inherent in these schemes. In response, employees took the initiative away from supervisors to ensure that performance criteria and indicators were specific and job-related. Employees were also aware of the importance of regular feedback during the appraisal cycle. The prime challenge for Australian public sector employees and their unions is seen to be the development of an approach to performance management that would serve to ameliorate the individualistic and competitive cast of individualized merit pay compensation processes, principally through the pur suit of procedural justice in the formulation and implementation ofsuch schemes
Unsupervised Domain Adaptation With Distribution Matching Machines

Domain adaptation generalizes a learning model across source domain and target domain that follow different distributions. Most existing work follows a two-step procedure: first, explores either feature matching or instance reweighting independently, and second, train the transfer classifier separately. In this paper, we show that either feature matching or instance reweighting can only reduce, but not remove, the cross-domain discrepancy, and the knowledge hidden in the relations between the data labels from the source and target domains is important for unsupervised domain adaptation. We propose a new Distribution Matching Machine (DMM) based on the structural risk minimization principle, which learns a transfer support vector machine by extracting invariant feature representations and estimating unbiased instance weights that jointly minimize the cross-domain distribution discrepancy. This leads to a robust transfer learner that performs well against both mismatched features and irrelevant instances. Our theoretical analysis proves that the proposed approach further reduces the generalization error bound of related domain adaptation methods. Comprehensive experiments validate that the DMM approach significantly outperforms competitive methods on standard domain adaptation benchmarks.
Effecting change in management culture

This article describes the outcome of a series of research-based organization development (OD) interventions used to bring about management culture change within one part of the British Civil Service. • The application of well-grounded and academically rigorous internal research findings to inform and shape the OD interventions designed to impact culture in support of strategic change are discussed. • The results reported lend support to the analysis of the concept of ‘cultural lag’ and its application. • It is argued that the credibility of the internal research base, derived from its academic credentials and the full commitment of a visionary leader, were significant factors in overcoming the restraining forces of ‘cultural lag’ applying at the time. • A case is made for more use within the UK of strategically led research-based approaches to management and organization development. © 1997 John Wiley & Sons, Ltd.
Gender Differences in the Experiences of African American College Students: The Effects of Co-ethnic Support and Campus Diversity

This study applies an intersectional framework to provide information about the ways in which race, gender, and on-campus social support influence the experiences of African American college students. Using the National Longitudinal Survey of Freshmen, I examine how co-ethnic social support from the college community and the college racial composition influence the experiences of African American students attending selective colleges. The results suggest that African American women and men are differentially influenced by co-ethnic support and college racial composition. African American women are more likely than are African American men to receive personal support from African American members of the campus community, take classes with African American professors, and participate in an African American student group. I also find that co-ethnic support is positively related to the academic and social experiences of African American women during college, and I find that the college satisfaction of African American women is positively related to campus diversity.
S-adenosyl-L-methionine for alcoholic liver diseases.

BACKGROUND Alcohol is a major cause of liver disease and disrupts methionine and oxidative balances. S-adenosyl-L-methionine (SAMe) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione, the main cellular antioxidant. Randomised clinical trials have addressed the question whether SAMe may benefit patients with alcoholic liver diseases. OBJECTIVES To evaluate the beneficial and harmful effects of SAMe for patients with alcoholic liver diseases. SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (May 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2005), MEDLINE (1950 to May 2005), EMBASE (1980 to May 2005), and Science Citation Index Expanded (searched May 2005). SELECTION CRITERIA We included randomised clinical trials studying patients with alcoholic liver diseases. Interventions encompassed per oral or parenteral administration of SAMe at any dose versus placebo or no intervention. DATA COLLECTION AND ANALYSIS We performed all analyses according to the intention-to-treat method using RevMan Analyses provided by the Cochrane Collaboration. We evaluated the methodological quality of the randomised clinical trials by quality components. MAIN RESULTS We identified nine randomised clinical trials including a heterogeneous sample of 434 patients with alcoholic liver diseases. The methodological quality regarding randomisation was generally low, but 8 out of 9 trials were placebo controlled. Only one trial including 123 patients with alcoholic cirrhosis used adequate methodology and reported clearly on all-cause mortality and liver transplantation. We found no significant effects of SAMe on all-cause mortality (relative risks (RR) 0.62, 95% confidence interval (CI) 0.30 to 1.26), liver-related mortality (RR 0.68, 95% CI 0.31 to 1.48), all-cause mortality or liver transplantation (RR 0.55; 95% CI 0.27 to 1.09), or complications (RR 1.35, 95% CI 0.84 to 2.16), but the analysis is based mostly on one trial only. SAMe was not significantly associated with non-serious adverse events (RR 4.92; 95% CI 0.59 to 40.89) and no serious adverse events were reported. AUTHORS' CONCLUSIONS We could not find evidence supporting or refuting the use of SAMe for patients with alcoholic liver diseases. We need more long-term, high-quality randomised trials on SAMe for these patients before SAMe may be recommended for clinical practice.