Miracle-dz/UniFAR-FTUs huggingface dataset:
Energy metabolism in single human muscle fibres during intermittent contraction with occluded circulation.

1. Glycogenolysis in type I and II muscle fibres was investigated in five healthy volunteers during electrical stimulation of the quadriceps muscle group with blood flow occluded. 2. The quadriceps femoris muscles were stimulated intermittently (1.6 s stimulation, 1.6 s rest) at a frequency of 50 Hz for 64 s and isometric contraction force was recorded. Muscle biopsies were obtained at rest prior to and immediately after stimulation. Single muscle fibres were dissected free and were identified as type I and II fibres. ATP, phosphocreatine (PCr) and glycogen contents were measured luminometrically and enzymatically in single fibres and mixed fibre muscle. 3. Electrical stimulation resulted in a marked decline in contraction force and near total depletion of PCr in both fibre types. The ATP turnover rate (P < 0.05) and the magnitude of the decline in ATP (P < 0.05) were greater in type II fibres. Prior to stimulation the muscle glycogen content was 32% higher in type II fibres compared with type I fibres (P < 0.01). During stimulation the rate of glycogenolysis in type II fibres (4.32 +/‐ 0.54 mmol (kg dry matter (DM)‐1 s‐1 was twofold greater than the rate in type I fibres (2.05 +/‐ 0.70 mmol (kg DM)‐1 s‐1, P < 0.05). 4. The data suggest that the relatively higher rate of glycogenolysis observed in type I fibres during intermittent electrical stimulation with occluded circulation (2.05 +/‐ 0.70 mmol (kg DM)‐1 s‐1), when compared with the corresponding rate recorded during intense contraction with circulation intact (0.18 +/‐ 0.14 mmol (kg DM)‐1 s‐1, P < 0.05), may result from an accelerated ATP turnover rate in this fibre type increasing the cellular concentrations of free AMP and inosine 5'‐monophosphate (IMP), which are known activators of glycogen phosphorylase. 5. The similarity in the rate of type II fibre glycogenolysis during contraction with circulatory occlusion (4.32 +/‐ 0.54 mmol (kg DM)‐1 s‐1), when compared with the corresponding rate recorded during non‐occluded circulation (3.54 +/‐ 0.53 mmol (kg DM)‐1 s‐1, P > 0.05), is in agreement with the suggestion that glycogenolysis in this fibre type is already occurring at a near‐maximal rate with circulation intact.
Expression and Secretion of Barley Cysteine Endopeptidase B and Cellobiohydrolase I in Trichoderma reesei

Localization of expression and secretion of a heterologous barley cysteine endopeptidase (EPB) and the homologous main cellobiohydrolase I (CBHI) in a Trichoderma reesei transformant expressing both proteins were studied. The transformant was grown on solid medium with Avicel cellulose and lactose to induce the cbh1 promoter for the synthesis of the native CBHI and the recombinant barley protein linked to a cbh1 expression cassette. Differences in localization of expression between the two proteins were clearly indicated by in situ hybridization, indirect immunofluorescence, and immunoelectron microscopy. In young hyphae, native-size recombinant epb mRNA was localized to apical compartments. In older cultures, it was also seen in subapical compartments but not in hyphae from the colony center. The recombinant EPB had a higher molecular weight than the native barley protein, probably due to glycosylation and differential processing in the fungal host. As was found with its transcripts, recombinant EPB was localized in apical and subapical compartments of hyphae. The cbh1 mRNA and CBHI were both localized to all hyphae of a colony, which suggests that the endogenous CBHI was also secreted from these. In immunoelectron microscopy, the endoplasmic reticulum and spherical vesicles assumed to contribute to secretion were labeled by both CBHI and EPB antibodies while only CBHI was localized in elongated vesicles close to the plasma membrane and in hyphal walls. The results indicate that in addition to young apical cells, more mature hyphae in a colony may secrete proteins.
The National Health Service Bowel Cancer Screening Program: the early years

The National Health Service Bowel Cancer Screening Program (NHS BCSP) was developed to improve outcomes from colorectal cancer, the third most frequent cancer and the second highest cause of cancer deaths in the UK. Screening pilot programs were developed after previous trials demonstrated a reduction in mortality with the use of fecal occult blood population screening. A successful pilot period led to the roll out of national biennial screening for all 60–69 year olds in 2006, and extended to 60–74 year olds in 2010. To the end of 2012, there have been over 16 million invitations to screening, with uptake of 55.35%. FOBt positivity was 2.08%. Almost 15,000 cancers have been identified; screen-detected cancers have been shown to be at an earlier stage than non-screen-detected, with 35% Dukes’ stage A. The BCSP provides high quality colonoscopy with low adverse events rates. It is also a rich data source for research.
Estimation of losses in semiconductors of power through simulation

This paper presents the development of a simulation methodology to estimate the losses in power semiconductors using PSIM® software and using it as an educational tool. The simulation of the losses is implemented using the curves and the data provided in the datasheets of semiconductors. To validate this methodology, two modulation strategies are applied to the HB/ANPC inverter, modified PD-PWM and modified CSV-PWM, making the inverter operate with half the switches at low frequency (60 Hz) and the other half in high frequency (1020 Hz). Therefore, they were chosen two types of semiconductor switches. First is explained the operation of the inverter used, then the study of conduction and switching losses on the switches and diodes in antiparallel. The analysis of the conduction losses, is used for voltage at the nominal power curves module operation. Whereas the switching losses is used the energy dissipated curves during the ligament and the shutdown of the switches. These losses are displayed in simulation blocks, which are detailed building blocks implemented through a didactic approach. Finally, a comparison between simulated losses using PSIM® software and mathematical methods are performed. Additionally a comparison between the two modulations is performed indicating which produces less loss.
The Economics of Advertising

A GOOD general dictionary tells you that advertising simply means making a thing widely known by circular, etc., but a scrupulously careful scientific handbook tells you that advertising means "the process of notifying or persuading people without personal solicitation" (italics ours). The difference between the two statements makes all the difference—notifying, yes, by all means; persuading, a much more hesitant yes. The kind of thing that bothers most people about advertising is the patent-medicine advertisement that blurs the distinction between palliatives and cures, the advertisement for pills that vulgarly disfigures a lovely landscape, the window-dressing that induces people to buy what they do not need and cannot afford. Evidently advertising touches psychology, ethics and æsthetics as well as economics. Of all this the author of this fine book is perfectly well aware. He promises to deal later on with "the various ethical and social problems raised by the practice of commercial advertising". In this volume he adheres to his purpose as indicated in the title. The book is packed with information and suggestions coming from one who is obviously master of his subject, who has lived it as well as studied it, and who helps the reader to form a judgment as to the immediate future of advertising.The Economics of AdvertisingF. P.BishopBy. Pp. 200. (London:Robert Hale, Ltd., 1944.) 7s. 6d. net.
Advances in Continuous Flow Left Ventricular Assist Device Support for End-Stage Heart Failure: A Therapy in Evolution

The purpose of this review is to highlight recent advances and challenges in the clinical implementation of continuous flow left ventricular assist devices (CF LVADs) in patients with advanced heart failure. Post approval studies of CF LVAD therapy continue to show a progressive improvement in survival and reduction in adverse events. Major trials are ongoing to compare outcomes of an axial flow device (Heart Mate II) and smaller centrifugal flow pumps (HeartWare VADs and Heart Mate III). Numerous studies have investigated strategies to reduce major hematologic and neurologic adverse events by evaluating hemolysis, antithrombotic therapy, and blood pressure control. This review will present the current findings that are centered around the impact of CF LVADs on improving survival and reducing adverse events through an evolution in management and design.
Efficacy of the Theory of Planned Behaviour: a meta-analytic review.

The Theory of Planned Behaviour (TPB) has received considerable attention in the literature. The present study is a quantitative integration and review of that research. From a database of 185 independent studies published up to the end of 1997, the TPB accounted for 27% and 39% of the variance in behaviour and intention, respectively. The perceived behavioural control (PBC) construct accounted for significant amounts of variance in intention and behaviour, independent of theory of reasoned action variables. When behaviour measures were self-reports, the TPB accounted for 11% more of the variance in behaviour than when behaviour measures were objective or observed (R2s = .31 and .21, respectively). Attitude, subjective norm and PBC account for significantly more of the variance in individuals' desires than intentions or self-predictions, but intentions and self-predictions were better predictors of behaviour. The subjective norm construct is generally found to be a weak predictor of intentions. This is partly attributable to a combination of poor measurement and the need for expansion of the normative component. The discussion focuses on ways in which current TPB research can be taken forward in the light of the present review.
Structure-activity relationships of selected phenazines against Mycobacterium leprae in vitro

Structure-activity relationships of phenazines against Mycobacterium leprae were investigated by using an in vitro radiorespirometric assay. In general, activity in ascending order was observed in compounds containing no chlorine atoms, a monochlorinated phenazine nucleus, and chlorines in the para positions of both the anilino and phenyl rings. The most active compounds contained a 2,2,6,6-tetramethylpiperidine substitution at the imino nitrogen. Most of these chlorinated phenazines were considerably more active in vitro than clofazimine (B663).
Beneficial effects and improved survival in rodent models of septic shock with S-methylisothiourea sulfate, a potent and selective inhibitor of inducible nitric oxide synthase.

Enhanced formation of nitric oxide (NO) by both the constitutive and the inducible isoforms of NO synthase (NOS) has been implicated in the pathophysiology of a variety of diseases, including circulatory shock. Non-isoform-selective inhibition of NO formation, however, may lead to side effects by inhibiting the constitutive isoform of NOS and, thus, the various physiological actions of NO. S-Methylisothiourea sulfate (SMT) is at least 10- to 30-fold more potent as an inhibitor of inducible NOS (iNOS) in immunostimulated cultured macrophages (EC50, 6 microM) and vascular smooth muscle cells (EC50, 2 microM) than NG-methyl-L-arginine (MeArg) or any other NOS inhibitor yet known. The effect of SMT on iNOS activity can be reversed by excess L-arginine in a concentration-dependent manner. SMT (up to 1 mM) does not inhibit the activity of xanthine oxidase, diaphorase, lactate dehydrogenase, monoamine oxidase, catalase, cytochrome P450, or superoxide dismutase. SMT is equipotent with MeArg in inhibiting the endothelial, constitutive isoform of NOS in vitro and causes increases in blood pressure similar to those produced by MeArg in normal rats. SMT, however, dose-dependently reverses (0.01-3 mg/kg) the hypotension and the vascular hyporeactivity to vasoconstrictor agents caused by endotoxin [bacterial lipopolysaccharide (LPS), 10 mg/kg, i.v. ] in anesthetized rats. Moreover, therapeutic administration of SMT (5 mg/kg, i.p., given 2 hr after LPS, 10 mg/kg, i.p.) attenuates the rises in plasma alanine and aspartate aminotransferases, bilirubin, and creatinine and also prevents hypocalcaemia when measured 6 hr after administration of LPS. SMT (1 mg/kg, i.p.) improves 24-hr survival of mice treated with a high dose of LPS (60 mg/kg, i.p.). Thus, SMT is a potent and selective inhibitor of iNOS and exerts beneficial effects in rodent models of septic shock. SMT, therefore, may have considerable value in the therapy of circulatory shock of various etiologies and other pathophysiological conditions associated with induction of iNOS.
Selective labeling of serotonin uptake sites in rat brain by [3H]citalopram contrasted to labeling of multiple sites by [3H]imipramine.

Citalopram is a potent and selective inhibitor of neuronal serotonin uptake. In rat brain membranes [3H]citalopram demonstrates saturable and reversible binding with a KD of 0.8 nM and a maximal number of binding sites (Bmax) of 570 fmol/mg of protein. The drug specificity for [3H]citalopram binding and synaptosomal serotonin uptake are closely correlated. Inhibition of [3H]citalopram binding by both serotonin and imipramine is consistent with a competitive interaction in both equilibrium and kinetic analyses. The autoradiographic pattern of [3H]citalopram binding sites closely resembles the distribution of serotonin. By contrast, detailed equilibrium-saturation analysis of [3H]imipramine binding reveals two binding components, i.e., high affinity (KD = 9 nM, Bmax = 420 fmol/mg of protein) and low affinity (KD = 553 nM, Bmax = 8560 fmol/mg of protein) sites. Specific [3H]imipramine binding, defined as the binding inhibited by 100 microM desipramine, is displaced only partially by serotonin. Various studies reveal that the serotonin-sensitive portion of binding corresponds to the high affinity sites of [3H]imipramine binding whereas the serotonin-insensitive binding corresponds to the low affinity sites. Lesioning of serotonin neurons with p-chloroamphetamine causes a large decrease in [3H]citalopram and serotonin-sensitive [3H]imipramine binding with only a small effect on serotonin-insensitive [3H]imipramine binding. The dissociation rate of [3H]imipramine or [3H]citalopram is not altered by citalopram, imipramine or serotonin up to concentrations of 10 microM. The regional distribution of serotonin sensitive [3H]imipramine high affinity binding sites closely resembles that of [3H]citalopram binding. (ABSTRACT TRUNCATED AT 250 WORDS)
Reintegration problems and treatment interests among Iraq and Afghanistan combat veterans receiving VA medical care.

OBJECTIVE The objectives of this study were to describe the prevalence and types of community reintegration problems among Iraq and Afghanistan combat veterans who receive U.S. Department of Veterans Affairs (VA) medical care, identify interests in interventions or information to promote readjustment to community life, and explore associations between probable posttraumatic stress disorder (PTSD) and reintegration problems and treatment interests. METHODS A national, stratified sample of Iraq-Afghanistan combat veterans receiving VA medical care responded to a mailed survey focused on community reintegration. Of 1,226 veterans surveyed, 754 (62%) responded. Prevalence and proportions were adjusted for potential nonresponse bias. RESULTS An estimated 25% to 56% of combat veterans who use VA services reported "some" to "extreme" difficulty in social functioning, productivity, community involvement, and self-care domains. At least one-third reported divorce, dangerous driving, increased substance use, and increased anger control problems since deployment. Almost all (96%) expressed interest in services to help readjust to civilian life (95% confidence interval [CI]=93%-99%). The most commonly preferred ways to receive reintegration services or information were at a VA facility, through the mail, and over the Internet. An estimated 41% (95% CI=36%-46%) screened positive for PTSD, and probable PTSD was associated with reporting more readjustment difficulties and expressing interest in more types of services, including traditional mental health services. CONCLUSIONS Iraq-Afghanistan combat veterans who already receive VA medical care reported multiple current reintegration problems and wanted services and information to help them readjust to community life. These concerns were particularly prevalent among those with probable PTSD. Research is needed to explore nontraditional modes of service delivery, including the Internet.
Neuroprotection by the Inhibition of Apoptosis

Accumulating evidence strongly suggests that apoptosis contributes to neuronal cell death in a variety of neurodegenerative contexts. Activation of the cysteine protease caspase‐3 appears to be a key event in the execution of apoptosis in the central nervous system (CNS). As a result, mice null for caspase‐3 display considerable neuronal expansion usually resulting in death by the second week of life. At present, 14 caspase family members have been identified and subdivided into three subgroups on the basis of preference for specific tetrapeptide motifs using a positional scanning combinatorial substrate library. Caspase‐3 is a group II member (2, 3, 7) categorized by an absolute substrate requirement for aspartic acid in the P4 position of the scissile bond. The preferred cleavage motif (DExD) for group II caspases is found in many structural, metabolic and repair proteins essential for cellular homeostasis. Consistent with the proposal that apoptosis plays a central in role human neurodegenerative disease, caspase‐3 activation has recently been observed in stroke, spinal cord trauma, head injury and Alzheimer's disease. Indeed, peptide‐based caspase inhibitors prevent neuronal loss in animal models of head injury and stroke suggesting that these compounds may be the forerunners of non‐peptide small molecules that halt apoptosis processes implicated in these neurodegenerative disorders. A clear link between an hereditary neurodegenerative disorder and failed caspase inhibition has recently been proposed for spinal muscular atrophy (SMA). In severe SMA, the neuronal specific inhibitor of apoptosis (IAP) family member known as NAIP is often dysfunctional due to missense and truncation mutations. IAPs such as NAIP potently block the enzymatic activity of group II caspases (3 and 7) suggesting that NAIP mutations may permit unopposed developmental apoptosis to occur in sensory and motor systems resulting in lethal muscular atrophy. Conversely, adenovirally‐mediated overexpression of NAIP or the X‐linked IAP called XIAP reduces the loss of CA1 hippocampal neurons following transient forebrain ischemia. Taken together, these findings suggest that anti‐apoptotic strategies may some day have utility in the treatment of neurodegenerative disease. The present review will summarize some of the recent evidence suggesting that apoptosis inhibitors may become a practical therapeutic approach for both acute and chronic neurodegenerative conditions.
Clinical Significance of Insulin Antibodies in Insulin-Treated Diabetic Patients

The prevalence and titers of insulin antibodies in insulin-treated patients have markedly decreased, mainly as a consequence of the improvements in the purity of insulin preparations and to a lesser degree because of the changes of species of insulin (human insulin). However, numerous patients still produce antibody levels that may alter insulin pharmacokinetics, leading to higher postprandial blood glucose levels and to an increased risk for delayed hypoglycemia. Although the effects of antibodies on long-term glycemic control are less clear, the metabolic consequences of altered pharmacokinetics are clinically evident in patients in whom near normoglycemia is the goal and who are treated predominantly with short-acting insulin. Lipoatrophy and immunological insulin resistance, which are also antibody-induced phenomena, have become rare. Whether pregnancies in diabetic mothers with antibodies carry an increased risk for serious or fatal complications is not clear; neonates of these mothers are probably at increased risk for neonatal hypoglycemia.
Inhibition of the Non-Mevalonate 1-Deoxy-ᴅ-xylulose-5-phosphate Pathway of Plant Isoprenoid Biosynthesis by Fosmidomycin

Abstract Various bacterial and plastidic plant terpenoids are synthesized via the non-mevalonate1-deoxy-ᴅ-xylulose-5-phosphate (DOXP) pathway. The antibiotic and herbicidal compound fosmidomycin is known to inhibit growth of several bacteria and plants, but so far its mode of action was unknown. Here we present data which demonstrate that the DOXP pathway of isoprenoid biosynthesis is efficiently blocked by fosmidomycin. The results point to the DOXP reductoisom erase as the probable target enzyme of fosmidomycin.
Recurrence of Spinal Ependymoma: Risk Factors and Long‐Term Survival

Study Design A study was conducted on 78 patients with spinal ependymoma. The authors divided the patients in two groups. Objectives The aim was to elicit the risk factors for recurrence and the fate of patients who underwent second operations. Summary of Background Data Group A is made up of 59 patients with no signs of recurrence at follow-up (median 14 years), and group B is made up of 19 patients who had undergone second operations because of relapses (follow-up median 12 years). Methods The clinical and therapeutic characteristics and survival of the two groups were compared statistically. Result Analysis of the series shows that the most important points in predicting recurrence are length of clinical history (P < 0.05), and type of excision (P < 0.001). Conclusion These factors proved to be closely interelated. In the event of recurrence, spinal ependymoma has an adverse prognosis.
inhibition attenuates myocardial injury and dysfunction following acute ischemia-reperfusion injury

Moss NC, Stansfield WE, Willis MS, Tang R, Selzman CH. IKK inhibition attenuates myocardial injury and dysfunction following acute ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 293: H2248–H2253, 2007. First published August 3, 2007;. doi:10.1152/ajpheart.00776. 2007. —Despite years of experimental and clinical research, myocardial ischemia-reperfusion (IR) remains an important cause of cardiac morbidity and mortality. The transcription factor nuclear factorB (NFB) has been implicated as a key mediator of reperfusion injury. Activation of NFB is dependent upon the phosphorylation of its inhibitor, I B , by the specific inhibitory B kinase (IKK) subunit, IKK . We hypothesized that specific antagonism of the NFB inflammatory pathway through IKK inhibition reduces acute myocardial damage following IR injury. C57BL/6 mice underwent left anterior descending (LAD) artery ligation and release in an experimental model of acute IR. Bay 65-1942, an ATP-competitive inhibitor that selectively targets IKK kinase activity, was administered intraperitoneally either prior to ischemia, at reperfusion, or 2 h after reperfusion. Compared with untreated animals, mice treated with IKK inhibition had significant reduction in left ventricular infarct size. Cardiac function was also preserved following pretreatment with IKK inhibition. These findings were further associated with decreased expression of phosphorylated I B and phosphorylated p65 in myocardial tissue. In addition, IKK inhibition decreased serum levels of TNFand IL-6, two prototypical downstream effectors of NFB activity. These results demonstrate that specific IKK inhibition can provide both acute and delayed cardioprotection and offers a clinically accessible target for preventing cardiac injury following IR.