Miracle-dz/UniFAR-FTUs huggingface dataset:
Leukemia inhibitory factor (LIF) potentiates antinociception activity and inhibits tolerance induction of opioids.

BACKGROUND The efficacy of opioids typically decreases after long-term use owing to the development of tolerance. Glial activation and the upregulation of proinflammatory cytokines are related to the induction of tolerance. We investigated the effect of leukemia inhibitory factor (LIF) on morphine analgesia and tolerance. METHODS LIF concentrations in rat spinal cords were measured by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) after morphine administration. LIF distribution was examined using confocal microscopy. To evaluate the effects of LIF on morphine analgesia and tolerance, LIF was intrathecally administered 30 min before morphine injection. The analgesic effect of morphine was evaluated by measuring tail-flick latency. Human LIF concentrations from the cerebrospinal fluid (CSF) of opioid tolerant patients were also determined by specific ELISA. RESULTS Chronic morphine administration upregulated LIF concentrations in rat spinal cords. Intrathecal injection of LIF potentiated the analgesic action of morphine. Patch clamp recording of spinal cord slices showed that LIF enhanced DAMGO ([D-Ala2, N-MePhe4, Gly-ol]-enkephalin)-induced outward potassium current. The development of tolerance was markedly suppressed by exogenous LIF, whereas neutralizing the endogenously released LIF with anti-LIF antibodies accelerated the tolerance induction. Moreover, LIF concentrations in the CSF of opioid-tolerant patients were higher than those in the opioid-naive controls. CONCLUSIONS Intrathecal administration of LIF potentiated morphine antinociceptive activity and attenuated the development of morphine tolerance. Upregulation of endogenously released LIF by long-term use of opioids might counterbalance the tolerance induction effects of other proinflammatory cytokines. LIF might be a novel drug candidate for inhibiting opioid tolerance induction.
The Protein Information Resource (PIR)

The Protein Information Resource (PIR) produces the largest, most comprehensive, annotated protein sequence database in the public domain, the PIR-International Protein Sequence Database, in collaboration with the Munich Information Center for Protein Sequences (MIPS) and the Japan International Protein Sequence Database (JIPID). The expanded PIR WWW site allows sequence similarity and text searching of the Protein Sequence Database and auxiliary databases. Several new web-based search engines combine searches of sequence similarity and database annotation to facilitate the analysis and functional identification of proteins. New capabilities for searching the PIR sequence databases include annotation-sorted search, domain search, combined global and domain search, and interactive text searches. The PIR-International databases and search tools are accessible on the PIR WWW site at http://pir.georgetown. edu and at the MIPS WWW site at http://www. mips.biochem. mpg.de. The PIR-International Protein Sequence Database and other files are also available by FTP.
Experimental Febrile Convulsions in Epileptic Chickens: The Anticonvulsant Effect of Elevated γ‐Aminobutyric Acid Concentrations

Summary: The high seizure susceptibility in epileptic chickens is due to an autosomal recessive mutation. In 3‐day‐old chicks homozygous for the epilepsy gene (epileptics), elevation of body temperature using microwave diathermy evoked an initial febrile seizure resembling the clonic seizures evoked in epileptic chicks by photic stimulation. After complete recovery, this was followed by a clonic‐tonic seizure. In nonepileptic heterozygote hatchmates (carriers) of the same age, only the latter seizure pattern was observed. In 16‐ to 17‐day‐old chicks of either phenotype, both seizure patterns were observed during hyperthermia. In all cases, the temperature at which seizures occurred was significantly lower in epileptic than in nonepileptic chicks, indicating a lower threshold for febrile seizures when there is an inherited predisposition to convulse. The occurrence of seizures was dependent on the body temperature and not on the rate of rise of temperature. Elevation of the brain γ‐aminobutyric acid (GABA) concentrations by administration of the GABA transaminase inhibitor γ‐vinyl GABA reduced the incidence of the initial febrile seizures and increased the latency in those birds that were not fully protected.
Estimating Production Functions of Multiproduct Firms

Despite the fact that multiproduct firms constitute a considerable share of firms and account for an even greater share of production, virtually all production function estimates are based on the assumption that firms are single-product producers. The single-product assumption is made due to lack of data on input allocation across the various product lines multiproduct firms operate. I provide a method to estimate product-level production functions without observable input allocations. The empirical application and Monte Carlo simulations show that the single-product firm assumption leads to biased parameter and productivity estimates and overestimated productivity differences between firms.
Calibrating a Market Model to Commodity and Interest Rate Risk

Based on the multi-currency LIBOR Market Model (LMM) this paper constructs a hybrid commodity interest rate market model with a time-dependent stochastic local volatility function allowing the model to simultaneously fit the implied volatility surfaces of commodity and interest rate options. Since liquid market prices are only available for options on commodity futures, rather than forwards, a convexity correction formula for the model is derived to account for the difference between forward and futures prices. A procedure for efficiently calibrating the model to interest rate and commodity volatility smiles is constructed. Finally, the model is fitted to an exogenously given correlation structure between forward interest rates and commodity prices (cross–correlation). When calibrating to options on forwards (rather than futures), the fitting of cross–correlation preserves the (separate) calibration in the two markets (interest rate and commodity options), while in the case of futures a (rapidly converging) iterative fitting procedure is presented. The fitting of cross–correlation is reduced to finding an optimal rotation of volatility vectors, which is shown to be an appropriately modified version of the “orthonormal Procrustes” problem in linear algebra. The calibration approach is demonstrated in an application to market data for oil futures.
Measuring Pediatric Bronchoscopy Outcomes Using an Electronic Medical Record.

RATIONALE Bronchoscopy procedures should be tracked for safety, quality improvement, and federal regulations. OBJECTIVE The aim of this study was to develop and test a method for evaluating flexible bronchoscopy use and outcomes using the electronic medical record (EMR) system in current clinical use at a large children's hospital. METHODS We created a custom bronchoscopy procedure note for our EMR system (Epic Systems Corporation) to track demographics, bronchoscopist, coordinated procedures, and outcome. Unplanned outcomes in children were defined as a disposition (admission to the hospital or elevation of care) after flexible bronchoscopy that differed from the preoperative plan. Readmissions to the hospital and emergency visits within our hospital system were also tracked electronically. Unplanned outcomes and readmissions were evaluated by a bronchoscopy quality team. MEASUREMENTS AND MAIN RESULTS Over 2.5 years, we tracked 1,297 bronchoscopic procedures performed on 1,161 patients (60% male, 78% American Society of Anesthesiologists class 2 or 3, mean age 5.5 yr [range, 0.02-40 yr]). Overall, 27 unplanned outcomes occurred (2.1%). The risk of unplanned outcomes did not appear to be different between procedures performed by a trainee with faculty oversight and those performed by a faculty member alone. Patients with multiple same-day procedures were more likely to have unplanned outcomes (21 of 27 [78%], P = 0.004) than were patients who had flexible bronchoscopy alone. The relative risk (RR) of having an unplanned outcome was not different from flexible bronchoscopy alone in the subset of patients with multiple procedures coordinated through our multidisciplinary aerodigestive clinic (RR 0.7; 95% CI, 0.1-3.4). The risk of unplanned events was significantly elevated in children with coordinated procedures scheduled outside the aerodigestive group (RR, 5.8; 95% CI, 2.4-14.5). Ten patients (<1%) were readmitted or seen urgently within 1 week; three of these unplanned outcomes were attributed to complications of the bronchoscopy. CONCLUSIONS An EMR system may be used to track procedural outcomes. Unplanned outcomes after flexible bronchoscopy were infrequent at our institution. Children who underwent multiple procedures had unplanned outcomes more often; however, the subset of children who underwent coordinated procedures through our multidisciplinary aerodigestive clinic did not demonstrate this increased risk.
Convergence of Connected Language and SPECT in Variants of Frontotemporal Lobar Degeneration

The characterization of frontotemporal lobar degeneration (FTLD) is complicated and not widely recognized. Connected language measures (ie, discourse) and functional neuroimaging may advance knowledge specifying early distinctions among frontal dementias. The present study examined the correspondence of discourse measures with (1) clinical diagnosis and (2) single photon emission computed tomography (SPECT) imaging. Nineteen subjects were selected from Alzheimer's Disease Center (ADC) participants if they were diagnosed with early-stage frontotemporal lobar degeneration and also underwent single photon emission computed tomography and discourse evaluation. First, clinical diagnoses given by specialists at an Alzheimer's Disease Center were compared with the discourse-based diagnostic profiles. Secondly, compromised brain regions that were predicted from discourse profiles were compared with SPECT findings. Results revealed a significant correspondence between the ADC diagnosis and the discourse-based diagnoses. Also, the discourse profiles across frontotemporal lobar degeneration subtypes were consistently associated with distinctive patterns of SPECT hypometabolism in the right frontal, left frontal, or left temporal lobes. These findings suggest that discourse methods may be systematized to provide an efficient adjunct measure beyond the traditional word and sentential level measures. Objectifying complex language performance may contribute to early detection and differentiation among frontotemporal lobar degeneration variants because consensus in the literature states that language is a core disturbance of frontotemporal lobar degeneration.
Fusion of a superfamily 1 helicase and an inactivated DNA polymerase is a signature of common evolutionary history of Polintons, polinton-like viruses, Tlr1 transposons and transpovirons

Abstract Polintons (polintoviruses), polinton-like viruses (PLVs) and virophages belong to a recently described major class of eukaryotic viruses that is characterized by a distinct virion morphogenetic protein module and, in many members, a protein-primed family B DNA polymerase (pDNAP). All Polintons, by definition, encode a pDNAP and a retrovirus-like integrase. Most of the PLV lack these genes and instead encode a large protein containing a superfamily 1 (SF1) helicase domain. We show here that the SF1 helicase domain-containing proteins of the PLV also contain an inactivated pDNAP domain. This unique helicase-pDNAP fusion is also encoded by transpovirons, enigmatic plasmid-like genetic elements that are associated with giant viruses of the family Mimiviridae. These findings indicate the directionality of evolution of different groups of viruses and mobile elements in the Polinton-centered class. We propose that the PLV evolved from a polinton via fusion of the pDNAP gene with a helicase gene that was accompanied by mutations in the pDNAP active site, likely resulting in inactivation of the polymerase activity. The transpovirons could have evolved from PLV via the loss of several genes including those encoding the morphogenetic module proteins. These findings reaffirm the central evolutionary position of the Polintons in the evolution of eukaryotic viruses and other mobile genetic elements.
Amphetamine Withdrawal: I. Reliability, Validity and Factor Structure of a Measure

Objective: The aim of this study was to create a short, reliable and valid questionnaire for the evaluation of amphetamine withdrawal, which we shall call the Amphetamine Withdrawal Questionnaire (AWQ). Method: Items of the AWQ included in this study were based on the fourth edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) and a comprehensive review. A field trial for assessing the reliability, validity and factor structure was conducted in outpatients and inpatients with amphetamine withdrawal. Results: Thirty and 102 patients’ data were included in the reliability-validity tests and the factor study, respectively. Due to the very low mean score of insomnia item, this item was excluded from subsequent analyses. The AWQ internal consistency was satisfactory with a Cronbach's alpha of 0.77. For test-retest reliability, a Spearman rank order correlation coefficient of the AWQ total score was 0.79. The AWQ total score for criterion validity was moderately correlated with the other two accepted measures. Principal component analysis, eigenvalue-one test and a varimax rotation performed to elicit the factors of AWQ yielded a three-factor model of AWQ: namely hyperarousal, reversed vegetative and anxiety factors. Conclusions: The AWQ is a short, reliable and valid measure for assessing amphetamine withdrawal symptoms. Further studies with a larger number of patients should be conducted to confirm the results of this factor analysis.
Aluminum for nonlinear plasmonics: Resonance-driven polarized luminescence of Al, Ag, and Au nanoantennas

Resonant optical antennas are ideal for nanoscale nonlinear optical interactions due to their inherent strong local field enhancement. Indeed second- and third-order nonlinear response of gold nanoparticles has been reported. Here we compare the on- and off-resonance properties of aluminum, silver, and gold nanoantennas, by measuring two-photon photoluminescence (TPPL). Remarkably, aluminum shows 2 orders of magnitude higher luminescence efficiency than silver or gold. Moreover, in striking contrast to gold, the aluminum emission largely preserves the linear incident polarization. Finally, we show the systematic resonance control of two-photon excitation and luminescence polarization by tuning the antenna width and length independently. Furthermore, we analyze this tuning of the polarization with the rod dimensions by measuring the angular emission of TPPL via back focal plane imaging. Our findings point to aluminum as a promising metal for nonlinear plasmonics.
Wave equation based algorithm for distributed eigenvector computation

We propose a novel distributed algorithm to compute eigenvectors and eigenvalues of the graph Laplacian matrix L. We prove that, by propagating waves through the graph, a local fast Fourier transform yields the local component of every eigenvector of L. For large graphs, the proposed algorithm is orders of magnitude faster than random walk based approaches. We prove the equivalence of the proposed algorithm to eigenvector computation and derive convergence rates. We also demonstrate its utility on a distributed estimation example.
Prospective validation of a risk score based on biological markers for predicting progression free survival in Binet stage A chronic lymphocytic leukemia patients: Results of the multicenter O‐CLL1‐GISL study

A risk score based on three biological features (CD38, ZAP‐70, and IGHV mutational status) was previously developed to predict progression‐free survival (PFS) in untreated Binet A CLL patients. Here we perform a score validation analysis in a prospective and independent cohort of patients. Biological markers (CD38, ZAP‐70, and IGHV mutational status) and gene expression profiles (GEP) of leukemic cells from CLL patients included in a prospective multicenter observational study (O‐CLL1‐GISL protocol, clinicaltrial.gov ID:NCT00917549) were used to assess the value and reproducibility of this score. To date, 468 Binet A patients were classified as low‐ (0 positive marker), intermediate‐ (1 positive marker), or high‐risk (2 or 3 positive markers) using the progression risk score. The 3‐year PFS probability was 91.7%, 82.9%, and 57.4% for low‐, intermediate‐, and high‐risk (P < 0.0001) cases, respectively. These values were similar to those found in the original cohort. At Cox multivariate analysis, Rai stage, absolute lymphocyte count, progression risk score, and β‐2 microglobulin maintained an independent prognostic impact on PFS. This score remained a predictor of progression when analysis was limited to 371 Rai 0 cases (P < 0.0001). Finally, the cells from the different CLL risk groups showed differences in their gene expression patterns. These results confirm the ability of this progression risk score to predict PFS among Binet A patients. The utility of the score was also extended by demonstrating that it retains prognostic value when applied exclusively to Rai 0 patients. Specific transcriptional patterns were significantly associated with risk groups. Am. J. Hematol. 89:743–750, 2014. © 2014 Wiley Periodicals, Inc.
Restriction of Porcine Endogenous Retrovirus by Porcine APOBEC3 Cytidine Deaminases

ABSTRACT Xenotransplantation of porcine cells, tissues, and organs shows promise to surmount the shortage of human donor materials. Among the barriers to pig-to-human xenotransplantation are porcine endogenous retroviruses (PERV) since functional representatives of the two polytropic classes, PERV-A and PERV-B, are able to infect human embryonic kidney cells in vitro, suggesting that a xenozoonosis in vivo could occur. To assess the capacity of human and porcine cells to counteract PERV infections, we analyzed human and porcine APOBEC3 (A3) proteins. This multigene family of cytidine deaminases contributes to the cellular intrinsic immunity and act as potent inhibitors of retroviruses and retrotransposons. Our data show that the porcine A3 gene locus on chromosome 5 consists of the two single-domain genes A3Z2 and A3Z3. The evolutionary relationships of the A3Z3 genes reflect the evolutionary history of mammals. The two A3 genes encode at least four different mRNAs: A3Z2, A3Z3, A3Z2-Z3, and A3Z2-Z3 splice variant A (SVA). Porcine and human A3s have been tested toward their antiretroviral activity against PERV and murine leukemia virus (MuLV) using novel single-round reporter viruses. The porcine A3Z2, A3Z3 and A3Z2-Z3 were packaged into PERV particles and inhibited PERV replication in a dose-dependent manner. The antiretroviral effect correlated with editing by the porcine A3s with a trinucleotide preference for 5′ TGC for A3Z2 and A3Z2-Z3 and 5′ CAC for A3Z3. These results strongly imply that human and porcine A3s could inhibit PERV replication in vivo, thereby reducing the risk of infection of human cells by PERV in the context of pig-to-human xenotransplantation.
Role of p38 mitogen-activated protein kinases in preconditioning: a detrimental factor or a protective kinase?

Preconditioning, the phenomenon whereby brief episodes of ischemia or pharmacological agents protect the myocardium against subsequent ischemic injury, consists of an early and a late phase.1 The early phase develops immediately and disappears within 1 to 2 hours of ischemic preconditioning stimulus, whereas the late phase, also known as the “second window” of protection, becomes manifest after 12 to 24 hours and lasts for 3 to 4 days. An understanding of the signaling mechanisms that trigger and mediate this cardioprotective phenomenon would have vast physiological and pathological implications. Accordingly, many recent studies have focused on the characterization and delineation of the signal transduction pathways (molecules) underlying the development and manifestation of both the early and late phases of preconditioning. The general hypothesis is that the preconditioning stimulus will induce the activation of a cascade of stress-responsive kinases, which in turn transduce the stress signal into the generation of a protective protein or activation of a protective kinase. In this context, the p38 mitogen-activated protein kinases (MAPKs), a family of stress-activated MAPKs,2 3 have been examined as the candidate kinases during preconditioning. In this issue of Circulation Research , Dana et al4 report that the adenosine A1 agonist 2-chloro- N 6-cyclopentyladenosine (CCPA) induces a late phase of preconditioning in rabbit hearts. Twenty-four hours after the transient activation of the adenosine A1 receptor, the myocardium exhibited a significant rise in the activity of p38 MAPK. The increased p38 MAPK activity was completely abolished when the infarct-sparing effect of CCPA was abrogated by either the protein kinase C (PKC) inhibitor chelerythrine or the tyrosine kinase inhibitor lavendustin A. …
A new analysis of technological leapfrogging:a perspective of complexity theory

The definition of technological leapfrogging is the starting point of the researches on technological leapfrogging.Understanding the subjects,features and the logic of technological development is essential for the definition.Complexity theory brings a new perspective for researchers to analyze the mechanism and connotation of technological leapfrogging,which is the theoretical basis for further researches in the area.
Testing the Excess Return Hypothesis: The Canadian Case

This study examines the relationship between stock returns and the term structure of interest rates in a Canadian setting. Following 132 The BRC Academy Journal of Business Vol. 6, No. 1 Zhou’s study of the US market (Federal Reserve Board, 1996), the hypothesis tested is the excess return hypothesis, which states that expected returns move one-for-one with interest rates. This relationship is explored using nominal and real return data for Canadian stocks and bonds. In addition, given the close relationship between the Canadian and US economies, the study examines the ability of US interest rates to predict Canadian stock returns. Using first differenced returns, the study finds that nominal Canadian interest rates have predictive power vis-a-vis nominal Canadian stock returns, but, unlike Zhou’s (1996) results for the US, the relationship is negative. This is also true when real returns are used. As for US interest rates and Canadian stock returns, the relationship is of mixed sign and mainly insignificant for both nominal and real stock returns and interest rates. The only evidence supporting the excess return hypothesis occurs when two-stage least squares, using the short-term interest rate as an instrumental variable, are used to regress real Canadian stock returns on real US interest rates. Finally, tests to determine whether the results are dependent on the period studied indicate that they are not sample-dependent. JEL Classification: G10