Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of enhanced ceramide generation in DNA damage and cell death in chemical hypoxic injury to LLC-PK1 cells.

BACKGROUND Ceramide has been implicated to be a second messenger in the cell signaling pathway involved in cell growth, proliferation, and apoptotic cell death. However, there is little information of a role of ceramide in DNA damage and cell death in hypoxic injury known to induce necrotic cell death. METHODS Ceramide generation was measured in LLC-PK1 cells exposed to chemical hypoxia with a mitochondrial electron transport inhibitor, antimycin A and glucose deprivation. The effect of inhibition of ceramide generation on chemical hypoxia-induced DNA damage and cell death and the effect of exogenous ceramide on cellular injury were also determined. RESULTS Chemical hypoxia resulted in a rapid increase in ceramide production prior to any evidence of DNA damage and cell death in LLC-PK1 cells. The inhibitor of ceramide synthase, fumonisin B1, provided a marked protection against chemical hypoxia-induced DNA strand breaks, DNA fragmentation and cell death. Fumonisin B1 did not affect adenosine triphosphate (ATP) depletion induced by antimycin A, suggesting that fumonisin B1 does not alter cellular uptake of antimycin A. We confirmed the ability of ceramide synthase inhibitor, fumonisin B1, to suppress chemical hypoxia-induced ceramide generation. Exposure of LLC-PK1 cells to synthetic ceramide, C2- and C6-ceramide, but not C2-dihydroceramide, the structural analog of C2-ceramide, resulted in DNA strand breaks, DNA fragmentation and cell death in a dose- and time-dependent manner similar to the effect of chemical hypoxia. CONCLUSIONS Our data indicate that ceramide is a key modulator for DNA damage and cell death in chemical hypoxia to renal tubular epithelial cells.
Endoscopic Ultrasound-assisted Bile Duct Access and Drainage: Multicenter, Long-term Analysis of Approach, Outcomes, and Complications of a Technique in Evolution

Background and Study Aims: When endoscopic retrograde cholangio-pancreatography fails, the bile duct is drained percutaneously or surgically. Evolution of endoscopic ultrasound (EUS) has provided the ability to visualize and also drain the biliary tree. The aim of this study was to review different techniques of EUS-guided bile duct access and drainage, and compare extrahepatic (EH) and intrahepatic (IH) approaches and benign with malignant indications. Patients and Methods: EUS-guided attempts at bile duct drainage from 6 international centers were reviewed. This is a multicenter, nonrandomized retrospective study. Results: Two hundred forty patients underwent EUS-guided bile duct access and drainage (EUS-BD) with a mean age of 67.3 years. The IH approach was used in 60% of the cases. In 99% of the subjects, a 19-G needle was used. Success was achieved in 87% cases, with a similar success rate in EH and IH approaches (84.3% vs. 90.4%; P=0.15). Metal stents were placed in 60% and plastic stents in 27% of the cases. A higher success rate was noted in malignant diseases compared with benign diseases (90.2% vs. 77.3%; P=0.02). Complications for all techniques included pneumoperitoneum 5%, bleeding 11%, bile leak/peritonitis 10%, and cholangitis 5%. No significant difference was noted between the IH and the EH approaches (32.6% vs. 35.6%; P=0.64), with similar rates in benign and malignant diseases (26.7% vs. 37.1%; P=0.19). Conclusions: The EUS-BD technique is currently limited by a lack of dedicated devices and large data reporting outcomes and complications. Larger prospective and multicenter studies are needed to better define the indications, outcomes, and complications. With greater experience and dedicated devices, EUS-BD can be an effective alternative.
Monetary Equilibria with Indivisible Goods

This paper uses a New Monetarist framework to study the trade of indivisible goods with divisible money in a frictional market. We first derive conditions under which stationary equilibrium exists, and then show that if equilibrium exits, it is unique. The uniqueness result is due to the commitment and coordination nature of the pricing mechanisms. Money is superneutral in the model with generalized Nash bargaining, but not with competitive search. Because of the superneutrality of money, monetary equilibrium in the generalized Nash bargaining model only exists for low values of nominal interest rate. With competitive search, monetary equilibrium exists for all i > 0
Adaptive DRX Scheme for beyond 3G Mobile Handsets

Beyond 3G mobile networks will be data service centric. It is anticipated that UE will stay in the Connected State relatively long while supporting data services, so efficient power saving mechanisms for the Connected State are more significant in order to prolong the active time of a handset. Discontinuous Reception (DRX) is a dominant approach for power saving in the Idle State and the Connected State. In this paper, a novel Counter-Driven Adaptive DRX (CDA-DRX) scheme is proposed and analyzed. It intends to present a generic and easy-to-implement adaptive DRX scheme that keeps up with the change of user activity level. This autonomous and adaptive power saving scheme distinguishes itself from all other researches surveyed so far from literature by minimizing signaling overhead and easy balancing between packet delivery latency and power saving performance according to QoS requirement of established data services.
Rigorous Q-factor formulation for one- and two-port passive linear networks from an oscillator noise spectrum viewpoint

This brief characterizes one- and two-port passive networks from the viewpoint of oscillator design. A linear circuit theory derives the spectral spread due to RF noise from active devices. The formulation finds a frequency derivative function of logarithmic immittance that plays the key role of dominating the spectrum behavior. This leads to an explicit definition of the Q factor by referring to Leeson's basic oscillator model. The derived definition can provide an effective criterion for circuit topology and parameter optimization in low-noise oscillator design.
Intelligent sliding-mode motion control using fuzzy wavelet networks for automatic 3D overhead cranes

This paper develops novel methodologies for modeling and designing an intelligent sliding-mode motion control of an automated 3D overhead crane. Lagrangian mechanics is used to establish a mathematical model of the crane which involved uncertain parameters. Intelligent sliding mode control using fuzzy wavelet neural networks and backstepping are used to propose a motion controller so as to maintain the nutation angle less than 4 degrees and achieve position control simultaneously. The robust performance and merit of the proposed controller are exemplified by conducting several simulations on the 3D overhead crane with actual crane parameters under three different loading conditions.
IgG Antibodies Against Common Gut Bacteria Are More Diagnostic for Crohn's Disease Than IgG Against Mannan or Flagellin

INTRODUCTIONAntibodies to baker's yeast (mannan) have been widely used to aid in diagnosis of Crohn's disease. Recently, there has been interest in antibodies against a flagellin from Clostridium coccoides subphylum. We hypothesized that reactivity with these antigens is a surrogate marker for a generalized increased IgG response against intestinal microbiota in Crohn's disease.METHODSWe compared the diagnostic utility of IgG antibodies against flagellin and mannan with two complex surface antigen preparations, one derived from B. vulgatus (Bv), the other from over 20 common mucosa-associated microbiota, a multibacterial membrane preparation (MBP). IgG antibodies were measured in sera from two age- and sex-matched populations: 120 Crohn's patients (CD) and 160 gastroenterology controls (CON) comprising 40 ulcerative colitis (UC) and 120 non-IBD patients.RESULTSIgG was elevated against all antigen preparations in Crohn's but statistical analysis of receiver operator characteristic (ROC) plots showed that IgG against the complex antigen preparations MBP and Bv had better diagnostic accuracy to distinguish the two populations (CD and CON) than IgG against mannan (P ≤ 0.01) or flagellin (P ≤ 0.04). Concentrations of antibody reactive with distinct individual antigens correlated weakly.DISCUSSIONThe findings support our hypothesis that measurement of IgG reactivity against individual antigens gives an indication of a generalized increased IgG response against individual intestinal microbiota in Crohn's, rather than measuring specific immune responses important for pathogenesis. The data are consistent with either a mucosal defect that facilitates increased exposure to microbial antigens or an altered immune response, both of which could occur due to known genetic and molecular defects in Crohn's disease.
A subpopulation of gonadotropin‐releasing hormone neurons in the adult mouse forebrain is γ‐Aminobutyric acidergic

Gonadotropin‐releasing hormone (GnRH) neurons play a pivotal role in reproductive function. GnRH is released in distinct pulses that are regulated by neurotransmitters or neuromodulators. With immunohistochemistry and GAD67‐GFP knockin mice, this study shows for the first time that a subset of GnRH neurons in the forebrain of adult mouse is γ‐aminobutyric acid (GABA)‐ergic. There is a gender difference in the percentage of GnRH neurons expressing GAD67‐GFP in female vs. male mice. The percentage of GnRH neurons expressing GAD67‐GFP decreased after castration of female mice and increased to the normal female level after estradiol treatment. The percentage of GnRH neurons expressing GAD67‐GFP did not change significantly in intact, castrated, or castration + testosterone propionate‐treated male mice. During the female estrous cycle, the percentage of GnRH neurons expressing GAD67‐GFP was higher during the estrous stage than during the diestrous stage. During sexual maturation of postnatal development, GnRH neurons did not express GAD67‐GFP until postnatal day (P) 15, and the gender differences were first detected at P30, which corresponds to the maturation stage. In conclusion, our data suggest that 1) a subset of GnRH neurons in mouse forebrain is GABA‐ergic, 2) expression of GAD67‐GFP in GnRH neurons is at least in part regulated by estrogen, and 3) GnRH neurons secrete GABA to regulate themselves. © 2015 Wiley Periodicals, Inc.
Urinary CTX-II levels are associated with radiographic subtypes of osteoarthritis in hip, knee, hand, and facet joints in subject with familial osteoarthritis at multiple sites: the GARP study

Objective: To assess the relation between the urinary concentrations of type II collagen C-telopeptide (UCTX-II) and radiographic signs of osteoarthritis (ROA) in the GARP (Genetics, Arthrosis and Progression) study. Methods: UCTX-II levels were measured in GARP study participants, who are sibling pairs predominantly with symptomatic osteoarthritis at multiple sites. Kellgren and Lawrence scores were used to assess ROA in the knees, hips, hands, and vertebral facet joints, and spinal disc degeneration. A proportionate score was made for each joint location, based on the number of joints with ROA. The sum total ROA score represents a measure of cartilage abnormalities within each patient. By using linear mixed models the total ROA score and the joint site specific ROA scores were correlated with the UCTX-II level. Results: In 302 subjects the mean (SD) and median (range) for UCTX-II were 265 (168) and 219 (1346) ng/mmol creatine, respectively. There was a significant association between the total ROA score and UCTX-II levels. Subsequent multivariate analysis showed that the joint site specific ROA score at all joint sites, except for spinal disc degeneration, contributed independently to this association. Conclusions: The total ROA score of GARP patients, representing cartilage abnormalities at the most prevalent ROA joint locations, showed an excellent correlation with UCTX-II levels. The specific ROA scores at the hip, hand, facet, and knee joints additively and independently explained this association. Even in patients with osteoarthritis at multiple sites, UCTX-II may be a sensitive quantitative marker of ROA.
Epigenetic regulation of human cancer/testis antigen gene, HAGE, in chronic myeloid leukemia.

BACKGROUND AND OBJECTIVES Cancer testis antigens (CTA) provide attractive targets for cancer-specific immunotherapy. Although CTA genes are expressed in some normal tissues, such as the testis, this immunologically protected site lacks MHC I expression and as such, does not present self antigens to T cells. To date, CTA genes have been shown to be expressed in a range of solid tumors via demethylation of their promoter CpG islands, but rarely in chronic myeloid leukemia (CML) or other hematologic malignancies. DESIGN AND METHODS In this study, the methylation status of the HAGE CTA gene promoter was analyzed by quantitative methylation-specific polymerase chain reaction (MSP) and sequencing in four Philadelphia-positive cell lines (TCC-S, K562, KU812 and KYO-1) and in CML samples taken from patients in chronic phase (CP n=215) or blast crisis (BC n=47). HAGE expression was assessed by quantitative reverse transcriptase-polymerase chain reaction. RESULTS The TCC-S cell line showed demethylation of HAGE that was associated with over-expression of this gene. HAGE hypomethylation was significantly more frequent in BC (46%) than in CP (22%) (p=0.01) and was correlated with high expression levels of HAGE transcripts (p<0.0001). Of note, in CP-CML, extensive HAGE hypomethylation was associated with poorer prognosis in terms of cytogenetic response to interferon (p=0.01) or imatinib (p=0.01), molecular response to imatinib (p=0.003) and progression-free survival (p=0.05). INTERPRETATIONS AND CONCLUSION: The methylation status of the HAGE promoter directly correlates with its expression in both CML cell lines and patients and is associated with advanced disease and poor outcome.
Modelling the Transient Response of Windings , Laminated Steel Cores and Electromagnetic Power Devices by Means of Lumped Circuits

Holmberg, P. 2000. Modelling the transient response of windings, laminated steel cores and electromagnetic power devices by means of lumped circuits. With special reference to windings with a coaxial insulation system. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 592. 97 pp. Uppsala. ISBN 91-554-4877-1 Electromagnetic transients impinging on electromagnetic power devices — such as electric machines, transformers and reactors — can stress the design severely. Thus the magnitudes of the transients are often decisive for the design of the devices. Further, the operation of a device can be transient in itself. This is the case for the explosive magnetic flux compression generator (EMG) and a ferromagnetic actuator. Models are presented that are mainly intended for transients in the millisecond range and faster. Hence, eddy currents and the related skin and proximity effect become significant in windings, magnetic cores and in the armatures of the devices. These effects are important for, e.g., the damping of the transients. Further, the displacement current in the insulation of the winding is significant. It changes the response of the windings dramatically, as it manifests the finite velocity of propagation of the electromagnetic fields. Under such circumstances, reflections and excited resonances can make the transient voltage and current distribution highly irregular. Induced voltages are modelled with self and mutual inductances or reluctances combined with winding templates. The displacement currents are modelled with capacitances or coefficients of potential. Cauer circuits and their dual form are used to model eddy currents in laminated cores and in conductors. The Cauer circuit enables one to consider hysteresis and the non-linear response of a magnetic core. It is also used to model the eddy currents in the moving armature of an EMG. A set-up is presented that can be used to study the transient voltage and the current distribution along a coil. The transient response of coaxially insulated windings is analysed and modelled in detail. A lumped circuit model is developed for a coil, Dryformer — the new high-voltage transformer — and Powerformer, the new high-voltage generator. An alternative model, a combined lumped circuit and FEM model, is presented for a coaxially insulated winding in two slot cores.
Decision Curve Analysis: A Novel Method for Evaluating Prediction Models

Background. Diagnostic and prognostic models are typically evaluated with measures of accuracy that do not address clinical consequences. Decision-analytic techniques allow assessment of clinical outcomes but often require collection of additional information and may be cumbersome to apply to models that yield a continuous result. The authors sought a method for evaluating and comparing prediction models that incorporates clinical consequences, requires only the data set on which the models are tested, and can be applied to models that have either continuous or dichotomous results. Method. The authors describe decision curve analysis, a simple, novel method of evaluating predictive models. They start by assuming that the threshold probability of a disease or event at which a patient would opt for treatment is informative of how the patient weighs the relative harms of a false-positive and a false-negative prediction. This theoretical relationship is then used to derive the net benefit of the model across different threshold probabilities. Plotting net benefit against threshold probability yields the “decision curve. ” The authors apply the method to models for the prediction of seminal vesicle invasion in prostate cancer patients. Decision curve analysis identified the range of threshold probabilities in which a model was of value, the magnitude of benefit, and which of several models was optimal. Conclusion. Decision curve analysis is a suitable method for evaluating alternative diagnostic and prognostic strategies that has advantages over other commonly used measures and techniques.
Development of β-Lapachone Prodrugs for Therapy Against Human Cancer Cells with Elevated NAD(P)H:Quinone Oxidoreductase 1 Levels

β-Lapachone, an o-naphthoquinone, induces a novel caspase- and p53-independent apoptotic pathway dependent on NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 reduces β-lapachone to an unstable hydroquinone that rapidly undergoes a two-step oxidation back to the parent compound, perpetuating a futile redox cycle. A deficiency or inhibition of NQO1 rendered cells resistant to β-lapachone. Thus, β-lapachone has great potential for the treatment of specific cancers with elevated NQO1 levels (e.g., breast, non–small cell lung, pancreatic, colon, and prostate cancers). We report the development of mono(arylimino) derivatives of β-lapachone as potential prodrugs. These derivatives are relatively nontoxic and not substrates for NQO1 when initially diluted in water. In solution, however, they undergo hydrolytic conversion to β-lapachone at rates dependent on the electron-withdrawing strength of their substituent groups and pH of the diluent. NQO1 enzyme assays, UV-visible spectrophotometry, high-performance liquid chromatography-electrospray ionization-mass spectrometry, and nuclear magnetic resonance analyses confirmed and monitored conversion of each derivative to β-lapachone. Once converted, β-lapachone derivatives caused NQO1-dependent, μ-calpain-mediated cell death in human cancer cells identical to that caused by β-lapachone. Interestingly, coadministration of N-acetyl-l-cysteine, prevented derivative-induced cytotoxicity but did not affect β-lapachone lethality. Nuclear magnetic resonance analyses indicated that prevention of β-lapachone derivative cytotoxicity was the result of direct modification of these derivatives by N-acetyl-l-cysteine, preventing their conversion to β-lapachone. The use of β-lapachone mono(arylimino) prodrug derivatives, or more specifically a derivative converted in a tumor-specific manner (i.e., in the acidic local environment of the tumor tissue), should reduce normal tissue toxicity while eliciting tumor-selective cell killing by NQO1 bioactivation.
Role of Monitoring and Blunting Coping Styles in Primary Insomnia

Objective: Primary insomnia is one of the most prevalent sleep disorders and assumed to be initiated and maintained, among other factors, by psychological variables such as coping strategies, sleep hygiene techniques, and arousability. Althouugh the number and kind of stressors seem to be important initiators of insomnia, individual coping dispositions appear to play a larger role in maintaining it. This study explores the relationship between different coping dispositions (monitoring/blunting) and insomnia. Monitoring refers to information-seeking behavior under threat; blunting pertains to distractive strategies utilized in situations implying threat or danger. Methods: The study compares 37 primary insomniacs (DSM IV criteria) and 47 good sleepers. Dependent measures included self-rating scales concerning sleep quality (Schlaffragebogen part B, Frankfurter Schlaffragebogen), coping styles (Frankfurt Monitoring Blunting Scales), and psychopathology (Neo Five Factors Inventory, Beck Anxiety Inventory). All measures had documented psychometric properties. Results: Primary insomniacs were significantly more likely to rigidly resort to monitoring strategies in controllable as well as uncontrollable situations. Further, 73% of all rigid monitors identified in the sample were rated as primary insomniacs, whereas 86% of all rigid Blunters were good sleepers. Insomniacs showed higher levels of anxiety than good sleepers, coping style groups differed in anxiety and neuroticism scores. Conclusion: The study further supports the hypothesis that a monitoring coping style is related to primary insomnia. Blunting appears to be a good predictor of high sleep quality. The results are discussed with regard to improving treatment for patients suffering from primary insomnia. DSM-IV = Diagnostic and Statistical Manual, Fourth Edition, Revised; SF-B = Schlaffragebogen part B; FSF = Frankfurter Schlaffragebogen; FMBS = Frankfurt Monitoring Blunting Scales; NEO FFI = Neo Five Factors Inventory; BAI = Beck Anxiety Inventory; TST = total sleep time; Mdn = Median; MANOVA = multivariate analysis of variance.