Miracle-dz/UniFAR-FTUs huggingface dataset:
Ryanodine receptor mutations in malignant hyperthermia and central core disease

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that manifests in response to anesthetic triggering agents. Central core disease (CCD) is a myopathy closely associated with MH. Both MH and CCD are primarily disorders of calcium regulation in skeletal muscle. The ryanodine receptor (RYR1) gene encodes the key channel which mediates calcium release in skeletal muscle during excitation–contraction coupling, and mutations in this gene are considered to account for susceptibility to MH (MHS) in more than 50% of cases and in the majority of CCD cases. To date, 22 missense mutations in the 15,117 bp coding region of the RYR1 cDNA have been found to segregate with the MHS trait, while a much smaller number of these mutations is associated with CCD. The majority of RYR1 mutations appear to be clustered in the N‐terminal amino acid residues 35‐614 (MH/CCD region 1) and the centrally located residues 2163‐2458 (MH/CCD region 2). The only mutation identified outside of these regions to date is a single mutation associated with a severe form of CCD in the highly conserved C‐terminus of the gene. All of the RYR1 mutations result in amino acid substitutions in the myoplasmic portion of the protein, with the exception of the mutation in the C‐terminus, which resides in the lumenal/transmembrane region. Functional analysis shows that MHS and CCD mutations produce RYR1 abnormalities that alter the channel kinetics for calcium inactivation and make the channel hyper‐ and hyposensitive to activating and inactivating ligands, respectively. The likely deciding factors in determining whether a particular RYR1 mutation results in MHS alone or MHS and CCD are: sensitivity of the RYR1 mutant proteins to agonists; the level of abnormal channel‐gating caused by the mutation; the consequential decrease in the size of the releasable calcium store and increase in resting concentration of calcium; and the level of compensation achieved by the muscle with respect to maintaining calcium homeostasis. From a diagnostic point of view, the ultimate goal of development of a simple non‐invasive test for routine diagnosis of MHS remains elusive. Attainment of this goal will require further detailed molecular genetic investigations aimed at solving heterogeneity and discordance issues in MHS; new initiatives aimed at identifying modulating factors that influence the penetrance of clinical MH in MHS individuals; and detailed studies aimed at describing the full epidemiological picture of in vitro responses of muscle to agents used in diagnosis of MH susceptibility. Hum Mutat 15:410–417, 2000. © 2000 Wiley‐Liss, Inc.
Information technology adoption in SMEs: an integrated framework

Purpose – The aim of this research is to gain a clearer understanding of information technology (IT) adoption in small and medium‐sized enterprises (SMEs) by analysing and contrasting the current literature. Whilst describing how and why SMEs acquire IT, the paper also seeks to highlight the enablers as well as the inhibitors that influence the adoption process.Design/methodology/approach – The method was a review of literature including empirical research and case studies related to IT adoption from various databases such as Business Premier, Science Direct, JStor and Emerald Insight. Supporting material was accessed from reference books regarding similar concepts and theories.Findings – The literature suggests that SMEs adopt IT for many reasons. In general, the majority of the changes result from pressures from both internal and external sources. In addition to these drivers, there are factors that influence the process either directly or indirectly. Based on these different perspectives the paper prop.
Pyrogeography and the Global Quest for Sustainable Fire Management

Fire is an ancient influence on the Earth system, affecting biogeochemical cycles and ecosystems. Humans have had a profound influence on global fire activity through setting and controlling fires, modifying the flammability of landscapes, and, more recently, changing the climate through the combustion of fossil fuels. We review this web of complex direct and indirect effects of fire on Earth using the framework provided by the emerging discipline of pyrogeography that unites biological, atmospheric, and social perspectives on fire. We describe the transition from fire activity before humans evolved, through the hunter-gatherer and agricultural phases, to the current period in Earth history dominated by industrialization (Anthropocene). We illustrate how pyrogeography provides the necessary framework to understand fire in the Anthropocene, including the management of pyrogenic emissions, protection of human life, conservation of biodiversity, and provision of ecosystem services.
Shellcode detector for malicious document hunting

Advanced Persistent Threat (APT) attacks became a major network threat in recent years. Among APT attack techniques, sending a phishing email with malicious documents attached is considered one of the most effective ones. Although many users have the impression that documents are harmless, a malicious document may in fact contain shellcode to attack victims. To cope with the problem, we design and implement a malicious document detector called Forensor to differentiate malicious documents. Forensor integrates several open-source tools and methods. It first introspects file format to retrieve objects inside the documents, and then automatically decrypts simple encryption methods, e.g., XOR, rot and shift, commonly used in malware to discover potential shellcode. The emulator is used to verify the presence of shellcode. If shellcode is discovered, the file is considered malicious. The experiment used 9,000 benign files and more than 10,000 malware samples from a well-known sample sharing website. The result shows no false negative and only 2 false positives.
Performance of schizophrenic patients in the Stroop Color Word Test and electrodermal responsiveness after acute administration of cannabidiol (CBD).

OBJECTIVE The last decade has seen increasing evidence of dysfunctions in the endogenous cannabinoid system in schizophrenia and of its relationship with the typical cognitive impairment of the disorder. Studies in animal models, healthy volunteers, and psychotic patients clearly suggest an antipsychotic-like effect of cannabidiol. This study investigated the effects of cannabidiol on selective attention in 28 schizophrenic patients using the Stroop Color Word Test and on these patients' electrodermal responsiveness to auditive stimuli. METHOD The subjects attended two experimental sessions, the first one without the administration of drugs. In the second session the subjects were divided into three groups that received either a single dose of cannabidiol 300 mg or cannabidiol 600 mg or placebo. RESULTS The three groups did not differ significantly with respect to electrodermal measures in the two experimental sessions. When the first and second sessions were compared improved performance was found in all three groups, with patients who received placebo and cannabidiol 300 mg performing better than those who received cannabidiol 600 mg. CONCLUSION The single, acute administration of cannabidiol seems to have no beneficial effects on the performance of schizophrenic patients in the Stroop Color Word Test, although the hypothesis that chronic administration may lead to improvement cannot be disregarded.
New Therapeutic Modality for Corneal Endothelial Disease Using Rho-Associated Kinase Inhibitor Eye Drops

Abstract: Corneal endothelial dysfunction accompanied by visual disturbance is a primary indication for corneal endothelial transplantation. However, despite the value and potential of endothelial graft surgery, a strictly pharmacological approach for treating corneal endothelial dysfunction remains an attractive proposition. Previously, we reported that the selective Rho-associated kinase (ROCK) inhibitor Y-27632 promotes cell adhesion and proliferation, and inhibits the apoptosis of primate corneal endothelial cells in culture. These findings have led us to develop a novel medical treatment for the early phase of corneal endothelial disease using ROCK inhibitor eye drops. In rabbit and monkey models of partial endothelial dysfunction, we showed that corneal endothelial wound healing was accelerated via the topical application of ROCK inhibitor to the ocular surface, resulting in the regeneration of a corneal endothelial monolayer with a high endothelial cell density. Based on these animal studies, we are now attempting to advance the clinical application of ROCK inhibitor eye drops for patients with corneal endothelial dysfunction. A pilot clinical study was performed at the Kyoto Prefectural University of Medicine, and the effects of Y-27632 eye drops after transcorneal freezing were evaluated in 8 patients with corneal endothelial dysfunction. We observed a positive effect of ROCK inhibitor eye drops in treating patients with central edema caused by Fuchs corneal endothelial dystrophy. We believe that our new findings will contribute to the establishment of a new approach for the treatment of corneal endothelial dysfunction.
International Evidence on the Long-Run Impact of Inflation

In this paper, I use a structural vector autoregression framework to analyze the effects of a permanent change in inflation on the long-run real interest rate and real output level in 14 industrialized countries. Long-run monetary superneutrality is rejected for all 14 countries using annual data: the results indicate that a permanent increase in inflation lowers the long-run real interest rate in each country; a permanent increase in inflation also increases the long-run real output level in a number of countries. Long-run monetary superneutrality is also rejected for four out of the five countries examined using quarterly data.
Early bone healing and biomechanical fixation of dual acid-etched and as-machined implants with healing chambers: an experimental study in dogs.

PURPOSE To evaluate the biomechanical fixation, bone-to-implant contact (BIC), and bone morphology of screw-type root-form implants with healing chambers with as-machined or dual acid-etched (DAE) surfaces in a canine model. MATERIALS AND METHODS The animal model included the placement of machined (n = 24) and DAE (n = 24) implants along the proximal tibiae of six mongrel dogs, which remained in place for 2 or 4 weeks. Following euthanasia, half of the specimens were subjected to biomechanical testing (torque to interface failure) and the other half were processed for histomorphologic and histomorphometric (%BIC) assessments. Statistical analyses were performed by one-way analysis of variance at the 95% confidence level and the Tukey post hoc test for multiple comparisons. RESULTS At 4 weeks, the DAE surface presented significantly higher mean values for torque to interface failure overall. A significant increase in %BIC values occurred for both groups over time. For both groups, bone formation through the classic appositional healing pathway was observed in regions where intimate contact between the implant and the osteotomy walls occurred immediately after implantation. Where contact-free spaces existed after implantation (healing chambers), an intramembranous-like healing mode with newly formed woven bone prevailed. CONCLUSIONS In the present short-term evaluation, no differences were observed in BIC between groups; however, an increase in biomechanical fixation was seen from 2 to 4 weeks with the DAE surface.
Option pricing for jump diffussion model with random volatility

Purpose - Option pricing based on Black-Scholes model is typically obtained under the assumption that the volatility of the return is a constant. The purpose of this paper is to develop a new method for pricing derivatives under the jump diffusion model with random volatility by viewing the call price as an expected value of a truncated lognormal distribution. Design/methodology/approach - Using Taylor series expansion the call price under random volatility is expressed as a function of kurtosis of the observed volatility process and applied to various class of GARCH models. Findings - A modified option pricing formula is developed for jump diffusion process model with random volatility. Originality/value - The main contribution of the paper is the development of a kurtosis-dependent option pricing formula for a jump diffusion model with random volatility.
Prima mangiare, poi filosofare

‘Prima mangiare’ (first, you need to be alive) takes a ‘from the inside out’ look at the abstracted formalism of ‘capabilities’ theorizing as well as at the prevailing development and welfare-planning, provision, delivery and ‘part’-icipation approaches to poverty alleviation. While outside intervention is indeed a moral imperative on the ‘do-your-share’ principle, there are vast geographical and demographic swathes where State or NGO-led public action do not reach. Even though autonomous human agency is subsumed in the ‘public action’ concept, ‘capabilities’ theorizing, while enunciating timely and valid principles about the ‘what’ (e.g. in UNDP's work), has little of immediately practical import to offer when it comes to the ‘how? ’: the excluded cannot ‘eat’ theory. Unlike ‘capabilities and functionings’, the latino (Moraisean) concept and practice of ‘capacitation’ offers the poor, starting with the excluded, both a theory and a practice by which they autonomously learn to become entrepreneurially and organizationally ‘literate’ in an increasingly competitive and globalizing world. Copyright © 2000 John Wiley & Sons, Ltd.
Lithium augmentation as an alternative to maintenance electroconvulsive therapy for recurrent major depressive disorder in older adults

Electroconvulsive therapy (ECT) is the gold standard treatment for treatment-resistant major depressive disorder (MDD); however, relapse rates can exceed 50% within the 12 months following ECT cessation.1 Pharmacotherapy is useful in reducing the need for further ECT, thus reducing exposure to its potential side-effects and complications. Lithium carbonate is the adjuvant agent best supported by clinical trials for use in treatment-resistant MDD.2
A deadlock prevention policy for FMS using mathematical programming

This paper focuses on the problem of deadlocks in automated flexible manufacturing systems (FMS). Based on Petri nets, a deadlock prevention policy is proposed for a special class of Petri nets, S3PR. We distinguish siphons in a net model by elementary and dependent ones. For each elementary siphon, a monitor is added to the plant model such that it is invariant controlled and the mathematical programming technique is employed to guarantee that no emptiable control-induced siphon is generated due to the addition of the monitor. This novel deadlock prevention policy can usually lead to a more permissive supervisor by adding a small number of monitors and arcs than the existing methods for the design of liveness enforcing Petri net supervisors. A flexible manufacturing example is utilized to illustrate the methods proposed in this paper.
A Game-Theoretic Analysis of Class Relationships and Economic Growth with Applications to Spain and Sweden*

In this paper, I try to answer two important and unsettled questions in contemporary political economy: (1) Is economic growth through cooperation between capital and labor possible without third party enforcement? ; and (2) What are the effects of strong labor power on obtaining cooperation and thus economic growth? I adopt a game-theoretic framework to address these questions in this paper. The theoretical findings suggest the following: (1) Under certain political, economic, and social conditions, capitalists will find it in their interest to invest at a maximum possible level and the labor will find it in their interest to claim as small a proportion of national output as possible. Under these circumstances, high level of investment, coupled with low worker claim over the national output, will create conditions favorable to economic growth; (2) In countries where political and economic conditions are such that workers feel pretty certain about their future, the strong labor can actually initiate economic growth by voluntarily lowering their claim over the national output. I show actual examples of class war, unstable class cooperation, and a sustained class cooperation in the last section of this paper.
Congressional Influence and Patterns of New Deal Spending, 1933-1939

T HE growth of the federal government in the United States in the twentieth century has been the subject of a spate of studies in recent years, each offering different positive interpretations of these developments. Other writers have concerned themselves with evaluating the normative implications of the increase in the size and scope of twentieth-century American government. However, virtually all of these various studies agree on at least one important point: the steady and rapid increase in the size of the federal government has occurred mostly since the period of the Great Depression in the 1930s. The modern federal transfer state first emerged from its "egg" during the New Deal, the period of rapid expansion in federal transfer programs associated with the Roosevelt administration's measures aimed at reliev-
A randomized, double-blind, placebo-controlled trial of the use of prednisolone as an adjunct to treatment in HIV-1-associated pleural tuberculosis.

BACKGROUND Active tuberculosis may accelerate progression of human immunodeficiency virus (HIV) infection by promoting viral replication in activated lymphocytes. Glucocorticoids are used in pleural tuberculosis to reduce inflammation-induced pathology, and their use also might reduce progression of HIV by suppressing immune activation. We examined the effect that prednisolone has on survival in HIV-1-associated pleural tuberculosis. METHODS We conducted a randomized, double-blind, placebo-controlled trial of prednisolone as an adjunct to tuberculosis treatment, in adults with HIV-1-associated pleural tuberculosis. The primary outcome was death. Analysis was by intention to treat. RESULTS Of 197 participants, 99 were assigned to the prednisolone group and 98 to the placebo group. The mortality rate was 21 deaths/100 person-years (pyr) in the prednisolone group and 25 deaths/100 pyr in the placebo group (age-, sex-, and initial CD4+ T cell count-adjusted mortality rate ratio, 0.99 [95% confidence interval, 0.62-1.56] [P =.95]). Resolution of tuberculosis was faster in the prednisolone group, but recurrence rates were slightly (though not significantly) higher, and use of prednisolone was associated with a significantly higher incidence of Kaposi sarcoma (4.2 cases/100 pyr, compared with 0 cases/100 pyr [P =.02]). CONCLUSIONS In view of the lack of survival benefit and the increased risk of Kaposi sarcoma, the use of prednisolone in HIV-associated tuberculous pleurisy is not recommended.
Trends in local government in Europe

Abstract The article explores which reform trends are expected to play a significant role in the further development of local government in European countries. Analysis is based on an adopted Delphi survey of (mainly academic) local government experts from thirty-two countries. Results include a list of trends structured by the perceived importance for the coming ten years. Redistributing responsibilities and duties across levels of government constitute the highest ratings out of all trends. Furthermore, results do not provide clear evidence to support a shift from public management to governance as has recently been proclaimed in academic debate and literature. Management topics continue to be of great importance. Last but not least, clusters extracted point to different reform groups, which highlight more reluctant or enthusiastic attitudes to the relevance of the suggested trends of the study.
Accurate Prediction and Validation of Response to Endocrine Therapy in Breast Cancer.

PURPOSE Aromatase inhibitors (AIs) have an established role in the treatment of breast cancer. Response rates are only 50% to 70% in the neoadjuvant setting and lower in advanced disease. Accurate biomarkers are urgently needed to predict response in these settings and to determine which individuals will benefit from adjuvant AI therapy. PATIENTS AND METHODS Pretreatment and on-treatment (after 2 weeks and 3 months) biopsies were obtained from 89 postmenopausal women who had estrogen receptor-alpha positive breast cancer and were receiving neoadjuvant letrozole for transcript profiling. Dynamic clinical response was assessed with use of three-dimensional ultrasound measurements. RESULTS The molecular response to letrozole was characterized and a four-gene classifier of clinical response was established (accuracy of 96%) on the basis of the level of two genes before treatment (one gene [IL6ST] was associated with immune signaling, and the other [NGFRAP1] was associated with apoptosis) and the level of two proliferation genes (ASPM, MCM4) after 2 weeks of therapy. The four-gene signature was found to be 91% accurate in a blinded, completely independent validation data set of patients treated with anastrozole. Matched 2-week on-treatment biopsies were associated with improved predictive power as compared with pretreatment biopsies alone. This signature also significantly predicted recurrence-free survival (P = .029) and breast cancer -specific survival (P = .009). We demonstrate that the test can also be performed with use of quantitative polymerase chain reaction or immunohistochemistry. CONCLUSION A four-gene predictive model of clinical response to AIs by 2 weeks has been generated and validated. Deregulated immune and apoptotic responses before treatment and cell proliferation that is not reduced 2 weeks after initiation of treatment are functional characteristics of breast tumors that do not respond to AIs.
Capacity constraints and cycles in property casualty insurance markets

Underwriting cycles are unexpected in a structurally competitive industry where financial capital is the major determinant of output capacity. "Arbitrage" theories explain underwriting cycles as largely an artifact of institutional lags and reporting practices; "capacity-constraint" theories view insurance markets as characterized by real frictions that cause underwriting cycles by temporarily reducing the industry's capacity to insure risks. Arbitrage theories imply no systematic relationship between capacity and underwriting margins, while capacity-constraint hypotheses predict a negative relationship. This article provides a test of the two theories by examining the empirical relationship between capacity and underwriting margins. The results, using data on four insurance lines, generally support the capacity-constraint hypothesis; unanticipated decreases in capacity cause higher profitability and prices.