Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro and ex vivo evaluation of second‐generation histone deacetylase inhibitors for the treatment of spinal muscular atrophy

Among a panel of histone deacetylase (HDAC) inhibitors investigated, suberoylanilide hydroxamic acid (SAHA) evolved as a potent and non‐toxic candidate drug for the treatment of spinal muscular atrophy (SMA), an α‐motoneurone disorder caused by insufficient survival motor neuron (SMN) protein levels. SAHA increased SMN levels at low micromolar concentrations in several neuroectodermal tissues, including rat hippocampal brain slices and motoneurone‐rich cell fractions, and its therapeutic capacity was confirmed using a novel human brain slice culture assay. SAHA activated survival motor neuron gene 2 (SMN2), the target gene for SMA therapy, and inhibited HDACs at submicromolar doses, providing evidence that SAHA is more efficient than the HDAC inhibitor valproic acid, which is under clinical investigation for SMA treatment. In contrast to SAHA, the compounds m‐Carboxycinnamic acid bis‐Hydroxamide, suberoyl bishydroxamic acid and M344 displayed unfavourable toxicity profiles, whereas MS‐275 failed to increase SMN levels. Clinical trials have revealed that SAHA, which is under investigation for cancer treatment, has a good oral bioavailability and is well tolerated, allowing in vivo concentrations shown to increase SMN levels to be achieved. Because SAHA crosses the blood–brain barrier, oral administration may allow deceleration of progressive α‐motoneurone degeneration by epigenetic SMN2 gene activation.
A Preliminary Investigation of Caffeinated Alcohol Use During Spring Break

ABSTRACT Background: Caffeinated alcoholic beverages (e.g., Red Bull and vodka) are popular but associated with negative consequences. CABs may be particularly popular during Spring Break, a potentially risky social event. Objectives: We aimed to identify the prevalence of Spring Break caffeinated alcohol use, determine how caffeinated alcohol use Spring Break drinking habits differ from usual, and examine the association between Spring Break caffeinated alcohol use and alcohol-related problems. Methods: Data were collected from 95 college students during March of 2013 and 2014. Students completed questionnaires of their alcohol and caffeinated alcohol use before and during Spring Break and Spring Break alcohol-related problems. Results: Approximately 54% of students used caffeinated alcohol during Spring Break. Spring Break caffeinated alcohol use was associated with more alcohol-related problems, even after controlling for other alcohol consumed and Spring Break vacation status. Conclusions/Importance: Caffeinated alcoholic beverages are commonly consumed during Spring Break and their use uniquely predicted harms. Prevention efforts placed on caffeinated alcoholic beverage users may be helpful in reducing Spring Break-related harms.
How Not to Rely on Moore's Law Alone: Low-Complexity Envelope-Tracking Amplifiers

Achieving fast wireless access speeds in an already restricted bandwidth (as the frequency spectrum is a finite resource) necessitates highly spectrally efficient communications standards that combine both amplitude-modulation (AM) and phase-modulation (PM). The resulting complex modulation schemes require that the RF power amplifier (PA) be highly linear to preserve the modulation and, hence, the transmitted data (in-band linearity) and simultaneously avoid interfering with users of the rest of the spectrum (out-of-band linearity). Unfortunately, in PA design, linearity and efficiency are contradictory goals; typically, highly linear PAs demonstrate low efficiency and, hence, reduced battery life [1].
Crude Democracy: Natural Resource Wealth and Political Regimes

1. Does oil promote democracy? 2. The foundations of rentier states 3. Resource rents and the political regime 4. Statistical tests on rents and the regime 5. The democratic effect of rents 6. Rentier democracy in comparative perspective 7. Theoretical extensions 8. Conclusion: whither the resource curse?
Measurements of an anomalous global methane increase during 1998

Measurements of atmospheric methane from a globally distributed network of air sampling sites indicate that the globally averaged CH4 growth rate increased from an average of 3.9 ppb yr−1 during 1995–1997 to 12.7±0.6 ppb in 1998. The global growth rate then decreased to 2.6±0.6 ppb during 1999, indicating that the large increase in 1998 was not a return to the larger growth rates observed during the late‐1970s and early‐1980s. The increased growth rate during 1998 corresponds to an increase in the imbalance between CH4 sources and sinks equal to ∼24 Tg CH4, the largest perturbation observed in 16 years of measurements. We suggest that wetland and boreal biomass burning sources may have contributed to the anomaly. An adaptation of a global process‐based model, which included soil‐temperature and precipitation anomalies, was used to calculate emission anomalies of 11.6 Tg CH4 from wetlands north of 30°N and 13 Tg CH4 for tropical wetlands during 1998 compared to average emissions calculated for 1982–1993. For 1999, calculated wetland emission anomalies were negative for high northern latitudes and the tropics, contributing to the low growth rate observed in 1999. Also 1998 was a severe fire year in boreal regions where ∼1.3 × 105 km² of forest and peat land burned releasing an estimated 5.7 Tg CH4.
The complete chloroplast genome sequence of Dieffenbachia seguine (Araceae)

Abstract The nucleotide sequence of the chloroplast genome from Dieffenbachia seguine is the first to have complete genome sequence from genus of Dieffenbachia family Araceae. The genome size is 163 699 bp in length, with 36.4% GC content. A pair of inverted repeats (IRs, 25 235 bp) is separated by a large single copy region (LSC, 90 780 bp) and a small single copy region (SSC, 22 449 bp). The chloroplast genome contains 113 unique genes, 88 protein-coding genes, 37 tRNA genes, and four rRNA genes. In these genes, 16 genes contained single intron and two genes composed of double introns. A maximum likelihood phylogenetic analysis using complete chloroplast genome revealed that Dieffenbachia seguine belongs to the Araceae family of the Arecidae group, which is conform to the traditional classification.
A Job Demands–Resources Approach to Public Service Motivation

This article uses job demands–resources theory to build a model of public service motivation (PSM). Public service motivation determines how employees in the public sector deal with their daily job demands and resources. Highly motivated public servants are able to deal with their job demands and prevent exhaustion. Additionally, because of their sense of calling, they are motivated to mobilize their job resources to stay engaged and perform well. However, if job demands are consistently high and job resources are consistently low, highly motivated public servants will lose their psychological resources, resulting in lower PSM. Reduced PSM, as a consequence, may strengthen the loss cycle of job demands and exhaustion and weaken the gain cycle of job resources and engagement. Public service managers and employees may use this model to optimize their work environment on a day-to-day basis.
Biotechnology and Bioengineering

Funding information National Key Research and Development Program of China, Grant/Award Number: 2017YFB0309302; Natural Science Foundation of China, Grant/Award Number: 31961133006; National Basic Research Program of China, Grant/Award Number: 2011CB707406 Abstract Toxic inhibitory compounds from lignocellulose pretreatment are the major obstacle to achieve high bioconversion efficiency in biorefinery fermentations. This study shows a unique glucose oxidation catalysis of Gluconobacter oxydans with its gluconic acid productivity free of inhibitor disturbance. The microbial experimentations and the transcriptome analysis revealed that both the activity of the membrane‐bound glucose dehydrogenase and the transcription level of the genes in periplasmic glucose oxidation respiratory chain of G. oxydans were essentially not affected in the presence of inhibitory compounds. G. oxydans also rapidly converted furan and phenolic aldehyde inhibitors into the less toxic alcohols or acids. The synergy of the robust periplasmic glucose oxidation and the rapid inhibitor conversion of G. oxydans significantly elevated the efficiency of the oxidative fermentation in lignocellulose hydrolysate. The corresponding genes responsible for the conversion of furan and phenolic aldehyde inhibitors were also mined by DNA microarrays. The synergistic mechanism of G. oxydans provided an important option of metabolic modification for enhancing inhibitor tolerance of general fermentation strains.
REAL STOCK PRICES AND THE LONG-RUN MONEY DEMAND FUNCTION IN MALAYSIA: Evidence from Error Correction Model

This study adopts the error correction model to empirically investigate the role of real stock prices in the long run-money demand in the Malaysian financial or money market for the period 1977: Q1-1997: Q2. Specifically, an attempt is made to check whether the real narrow money (M1/P) is cointegrated with the selected variables like industrial production index (IPI), one-year T-Bill rates (TB12), and real stock prices (RSP). If a cointegration between the variables, i.e., the dependent and independent variables, is found to be the case, it may imply that there exists a long-run co-movement among these variables in the Malaysian money market. From the empirical results it is found that the cointegration between money demand and real stock prices (RSP) is positive, implying that in the long run there is a positive association between real stock prices (RSP) and demand for real narrow money (M1/P). The policy implication that can be extracted from this study is that an increase in stock prices is likely to necessitate an expansionary monetary policy to prevent nominal income or inflation target from undershooting.
Impact of a code stroke protocol on the door-to-needle time for IV thrombolysis: a feasibility study

ABSTRACT Introduction Stroke is a development of an acute focal neurological deficit with an ischemic or hemorrhagic origin. Thrombolysis within 4.5 h of ischemic stroke onset improves outcome. Guidelines recommend administration of intravenous recombinant tissue plasminogen activator within 60 min upon arrival at the hospital, meaning the door-to-needle time (DNT) should be less than 60 min. In this study, a stroke protocol was introduced at the emergency department of the Ghent University Hospital with a primary goal to shorten the DNT. Methodology This study was an uncontrolled before-after cohort study. A ‘Code Stroke’ protocol (CSP) was implemented and the results from the pre-code stroke protocol period (Pre-CSP period, from 15 August 2016 until 5 March 2017) were compared with the results from the post-code stroke protocol period (Post-CSP period, from 6 March 2017 until 16 July 2017). Results The median DNT decreased significantly from 57 min in the Pre-CSP period to 33 min in the Post-CSP period (p < 0.001). The door-to-triage time (DTT), triage-to-emergency physician time (TET), emergency physician-to-CT time (ECT) and CT-to needle time (CNT) decreased significantly Post-CSP compared to Pre-CSP. When adjusting the results for other variables that might have an influence on these time intervals, the TET, ECT and CNT also decreased significantly. There was a statistically significant effect of the implementation of the CSP on the number of patients treated with a DNT within 20, 30, 45 and 60 min (p = 0.008). Conclusion A significant decrease in DNT can be achieved with the implementation of this stroke protocol.
Regional Shape Abnormalities in Thalamus and Verbal Memory Impairment After Subcortical Infarction

Background. Subcortical infarcts can result in verbal memory impairment, but the potential underlying mechanisms remain unknown. Objective. We investigated the spatiotemporal deterioration patterns of brain structures in patients with subcortical infarction and identified the regions that contributed to verbal memory impairment. Methods. Cognitive assessment and structural magnetic resonance imaging were performed 1, 4, and 12 weeks after stroke onset in 28 left-hemisphere and 22 right-hemisphere stroke patients with subcortical infarction. Whole-brain volumetric analysis combined with a further-refined shape analysis was conducted to analyze longitudinal morphometric changes in brain structures and their relationship to verbal memory performance. Results. Between weeks 1 and 12, significant volume decreases in the ipsilesional basal ganglia, inferior white matter, and thalamus were found in the left-hemisphere stroke group. Among those 3 structures, only the change rate of the thalamus volume was significantly correlated with that in immediate recall. For the right-hemisphere stroke group, only the ipsilesional basal ganglia survived the week 1 to week 12 group comparison, but its change rate was not significantly correlated with the verbal memory change rate. Shape analysis of the thalamus revealed atrophies of the ipsilesional thalamic subregions connected to the prefrontal, temporal, and premotor cortices in the left-hemisphere stroke group and positive correlations between the rates of those atrophies and the change rate in immediate recall. Conclusions. Secondary damage to the thalamus, especially to the left subregions connected to specific cortices, may be associated with early verbal memory impairment following an acute subcortical infarct.
The complete mitochondrial genome of the orb-weaver spider Cyclosa argenteoalba Boes. et Str. (Araneae: Araneidae)

Abstract The complete mitochondrial genome of an orb-weaver spider Cyclosa argenteoalba is determined in this article. The genome encodes the same 37 genes with a length of 14,575 bp as all other metazoan mitogenomes. The A + T content of the majority strand is 73.1%. Among the protein-coding genes, one gene (COI) begins with TTA, three (COII, COIII and ND6) start with ATT, three (ATP6, ND3 and ND4) begin with ATA and other six genes use ATT as initiation codon. All the protein-coding genes end with the canonical termination codons (TAA or TAG), except for ND3 and ND4L, which use an incomplete stop codon (T). Thirteen transfer RNAs genes lack the potential to form the cloverleaf-shaped secondary structure. The A + T-rich region is 1052 bp in length with an A + T content of 68.9%. In the phylogenetic analyses, C. argenteoalba was nested within Araneidae and the species from the superfamily Araneoidea form a momophyletic group.
Traffic-aware VDC embedding in data center: A case study of fattree

Virtualization is a common technology for resource sharing in data center. To make efficient use of data center resources, the key challenge is to map customer demands (modeled as virtual data center, VDC) to the physical data center effectively. In this paper, we focus on this problem. Distinct with previous works, our study of VDC embedding problem is under the assumption that switch resource is the bottleneck of data center networks (DCNs). To this end, we not only propose relative cost to evaluate embedding strategy, decouple embedding problem into VM placement with marginal resource assignment and virtual link mapping with decided source-destination based on the property of fat-tree, but also design the traffic aware embedding algorithm (TAE) and first fit virtual link mapping (FFLM) to map virtual data center requests to a physical data center. Simulation results show that TAE+FFLM could increase acceptance rate and reduce network cost (about 49% in the case) at the same time. The traffic aware embedding algorithm reduces the load of core-link traffic and brings the optimization opportunity for data center network energy conservation.
Advancing Concussion Assessment in Pediatrics (A-CAP): a prospective, concurrent cohort, longitudinal study of mild traumatic brain injury in children: study protocol

Introduction Paediatric mild traumatic brain injury (mTBI) is a public health burden. Clinicians urgently need evidence-based guidance to manage mTBI, but gold standards for diagnosing and predicting the outcomes of mTBI are lacking. The objective of the Advancing Concussion Assessment in Pediatrics (A-CAP) study is to assess a broad pool of neurobiological and psychosocial markers to examine associations with postinjury outcomes in a large sample of children with either mTBI or orthopaedic injury (OI), with the goal of improving the diagnosis and prognostication of outcomes of paediatric mTBI. Methods and analysis A-CAP is a prospective, longitudinal cohort study of children aged 8.00–16.99 years with either mTBI or OI, recruited during acute emergency department (ED) visits at five sites from the Pediatric Emergency Research Canada network. Injury information is collected in the ED; follow-up assessments at 10 days and 3 and 6 months postinjury measure a variety of neurobiological and psychosocial markers, covariates/confounders and outcomes. Weekly postconcussive symptom ratings are obtained electronically. Recruitment began in September 2016 and will occur for approximately 24 months. Analyses will test the major hypotheses that neurobiological and psychosocial markers can: (1) differentiate mTBI from OI and (2) predict outcomes of mTBI. Models initially will focus within domains (eg, genes, imaging biomarkers, psychosocial markers), followed by multivariable modelling across domains. The planned sample size (700 mTBI, 300 OI) provides adequate statistical power and allows for internal cross-validation of some analyses. Ethics and dissemination The ethics boards at all participating institutions have approved the study and all participants and their parents will provide informed consent or assent. Dissemination will follow an integrated knowledge translation plan, with study findings presented at scientific conferences and in multiple manuscripts in peer-reviewed journals.
Were Stocks During the Financial Crisis More Jumpy: A Comparative Study

This paper empirically analysis the price jump behavior of heavily traded US stocks during the recent financial crisis. Namely, I test the hypothesis that the recent financial turmoil caused no change in the price jump behavior. To accomplish this, I employ data on realized trades for 16 stocks and one ETF from the NYSE database. These data are at a 1-minute frequency and span the period from January 2008 to the end of July 2009, where the recent financial crisis is generally understood to start with the plunge of Lehman Brothers shares on September 9, 2008. I employ five model-independent and three model-dependent price jump indicators to robustly assess the price jump behavior. The results confirm an increase in overall volatility during the recent financial crisis; however, the results cannot reject the hypothesis that there was no change in price jump behavior in the data during the financial crisis. This implies that the uncertainty during the crisis was scaled up but the structure of the uncertainty seems to be the same.
Systemic lupus erythematosus diagnosis and management

SLE presents many challenges for clinicians. The onset of disease may be insidious, with many different symptoms and signs, making early and accurate diagnosis challenging. Tests for SLE in the early stages lack specificity; those that are useful later often appear only after organ damage is manifest. Disease patterns are highly variable; flares are not predictable and not always associated with biomarkers. Children with SLE may have severe disease and present special management issues. Older SLE patients have complicating co-morbid conditions. Therapeutic interventions have improved over recent decades, but available drugs do not adequately control disease in many patients, and successful outcomes are limited by off-target effects; some of these become manifest with longer duration of treatment, now in part revealed by improved rates of survival. Despite all of these challenges, advances in understanding the biological basis of SLE have translated into more effective approaches to patient care. This review considers the current state of SLE diagnosis and management, with a focus on new approaches and anticipated advances.
TLR2 Agonist Ameliorates Established Allergic Airway Inflammation by Promoting Th1 Response and Not via Regulatory T Cells1

TLRs are primary sensors of both innate and adaptive immune systems, where they play a pivotal role in the response directed against structurally conserved components of pathogens. Synthetic bacterial lipopeptide Pam3CSK4 is a TLR2 agonist capable of modulating Th1 and Th2 responses. This study examines the therapeutic effect of Pam3CSK4 in established airway inflammation in a murine model of asthma. In mice previously sensitized and challenged with OVA, Pam3CSK4 given i.p. markedly reduced the total inflammatory cell infiltrate and eosinophilia in bronchoalveolar lavage fluid. Pam3CSK4 therapy was associated with a reduction in OVA-induced IL-4 and IL-5 secretion from thoracic lymph node culture, airways inflammation, bronchial hyperresponsiveness, and serum levels of IgE. Pam3CSK4 therapy was also associated with an increase in OVA-induced IFN-γ, IL-12, and IL-10 production. However, the anti-inflammatory effect of Pam3CSK4 was independent of IL-10 or TGF-β, but was critically dependent on IL-12, the production of which by dendritic cells was enhanced by Pam3CSK4 in vitro. Our results provide direct evidence that Pam3CSK4 could represent a novel therapeutic agent in allergic airways disease.
Client focus in regulatory agencies

Abstract ‘Client focus’ seems like a counter-intuitive notion for regulatory agencies, whose job is to compel people to comply with government requirements. Yet it is becoming the catchphrase for many regulatory authorities. This article puts forward an argument, based on social exchange and regulatory theory, that a client-focused approach is not only compatible with a regulatory role, but also actually facilitates it. It recognizes that most people's propensity to comply is a function of factors other than the fear of punishment, such as their intrinsic or normative motivations and their ability to do what is required. It also assists in delineation and understanding of the proportion of regulatees who opportunistically avoid their obligations. The article advances a broader model of social exchange between regulators and regulatees.