Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonnucleoside Inhibitors of Norovirus RNA Polymerase: Scaffolds for Rational Drug Design

ABSTRACT Norovirus (NoV) is the leading cause of acute gastroenteritis worldwide, causing over 200,000 deaths a year. NoV is nonenveloped, with a single-stranded RNA genome, and is primarily transmitted person to person. The viral RNA-dependent RNA polymerase (RdRp) is critical for the production of genomic and subgenomic RNA and is therefore a prime target for antiviral therapies. Using high-throughput screening, nearly 20,000 “lead-like” compounds were tested for inhibitory activity against the NoV genogroup II, genotype 4 (GII.4) RdRp. The four most potent hits demonstrated half-maximal inhibitory concentrations (IC50s) between 5.0 μM and 9.8 μM against the target RdRp. Compounds NIC02 and NIC04 revealed a mixed mode of inhibition, while NIC10 and NIC12 were uncompetitive RdRp inhibitors. When examined using enzymes from related viruses, NIC02 demonstrated broad inhibitory activity while NIC04 was the most specific GII.4 RdRp inhibitor. The antiviral activity was examined using available NoV cell culture models; the GI.1 replicon and the infectious GV.1 murine norovirus (MNV). NIC02 and NIC04 inhibited the replication of the GI.1 replicon, with 50% effective concentrations (EC50s) of 30.1 μM and 71.1 μM, respectively, while NIC10 and NIC12 had no observable effect on the NoV GI.1 replicon. In the MNV model, NIC02 reduced plaque numbers, size, and viral RNA levels in a dose-dependent manner (EC50s between 2.3 μM and 4.8 μM). The remaining three compounds also reduced MNV replication, although with higher EC50s, ranging from 32 μM to 38 μM. In summary, we have identified novel nonnucleoside inhibitor scaffolds that will provide a starting framework for the development and future optimization of targeted antivirals against NoV.
Conditional Mean Jumps, Intraday Periodicity and Long Memory Volatility in High Frequency European Foreign Exchange Rates: Application of a FIGARCH model with a Bernoulli Jump Process

This paper investigates the intriguing features of high frequency European exchange rates during 1996. In addition to the well know intraday periodicity and long memory property in the volatility process, the conditional mean jumps appear to be significant in the high frequency exchange rates so that the usual normality assumption is found not to be adequate. Hence, this paper relies on a normal mixture distribution that allows for Bernoulli jumps in the process of the high frequency exchange rates. This mixture distribution is found that the jumps are closely related to the intraday periodicity and that they appear to be important for the estimation of the long memory property in the volatility process of the high frequency exchange rates. In particular, the jump probability seems to induce higher long memory parameters.
Outliers in American juvenile justice: the need for statutory reform in North Carolina and New York

Abstract There is a well-established and growing body of evidence from research that adolescents who commit crimes differ in many regards from their adult counterparts and are more susceptible to the negative effects of adjudication and incarceration in adult criminal justice systems. The age of criminal court jurisdiction in the United States has varied throughout history; yet, there are only two remaining states, New York and North Carolina, that continue to automatically charge 16 year olds as adults. This review traces the statutory history of juvenile justice in these two states with an emphasis on political and social factors that have contributed to their outlier status related to the age of criminal court jurisdiction. The neurobiological, psychological, and developmental aspects of the adolescent brain and personality, and how those issues relate both to a greater likelihood of rehabilitation in appropriate settings and to greater vulnerability in adult correctional facilities, are also reviewed. The importance of raising the age in New York and North Carolina not only lies in protecting incarcerated youths but also in preventing the associated stigma following release. Mental health practitioners are vital to the process of local and national juvenile justice reform. They can serve as experts on and advocates for appropriate mental health care and as experts on the adverse effects of the adult criminal justice system on adolescents.
Highly efficient damage-free correction of thickness distribution of quartz crystal wafers by atmospheric pressure plasma etching

A new finishing method was developed to correct the thickness distribution of a quartz crystal wafer by the numerically controlled scanning of a localized atmospheric pressure plasma. The thickness uniformity level of a commercially available AT-cut quartz crystal wafer was improved to less than 50 nm without any subsurface damage by applying one correction process. Furthermore, applying a pulse-modulated plasma markedly decreased the correction time of the thickness distribution without breaking the quartz crystal wafer by thermal stress.
The Effect of Traumatic Brain Injury on the Timing of Sleep

While there have been single case reports of the development of circadian rhythm sleep disorders, most commonly delayed sleep phase syndrome following traumatic brain injury (TBI), to our knowledge there have been no group investigations of changes to sleep timing in this population. The aim of the present study was to investigate sleep timing following TBI using the dim light melatonin onset (DLMO) as a marker of circadian phase and the Morningness‐Eveningness Questionnaire (MEQ) as a measure of sleep‐wake behavior. A sleep‐wake diary was also completed. It was hypothesized that the timing of DLMO would be delayed and that there would be a greater tendency toward eveningness on the MEQ in a post‐acute TBI group (n=10) compared to a gender and age matched control group. Participants were recruited at routine outpatient review appointments (TBI) and from the general population (control) as part of a larger study. They attended the sleep laboratory where questionnaires were completed, some retrospectively, and saliva melatonin samples were collected half‐hourly according to a standard protocol. The results show that the TBI and control groups reported similar habitual sleep times and this was reflected on the MEQ. There was, however, significant variability in the TBI group's change from the pre‐injury to the current MEQ score. The timing of melatonin onset was not different between the groups. While subtle changes (advances or delays) in this small sample may have cancelled each other out, the present study does not provide conclusive objective evidence of shift in circadian timing of sleep following TBI. Furthermore, although participants did report sleep timing changes, it is concluded that the MEQ may not be suitable for use with this cognitively impaired clinical group.
Association between Metformin Use and Coronary Artery Calcification in Type 2 Diabetic Patients

Objectives Type 2 diabetes mellitus (T2DM) is associated with coronary artery calcification (CAC) which is an independent risk factor for cardiovascular events. Metformin is the first-line antidiabetic medication. We aimed to investigate the association between metformin use and CAC. Methods We included 369 patients with T2DM in this cross-sectional study. CAC scores, clinical characteristics, and antidiabetic drug prescription information of the patients were acquired. Baseline parameters were balanced for metformin and nonmetformin users using the propensity score matching (PSM) strategy. Results Among the 369 subjects who met our inclusion criteria, 288 subjects were included for further analysis after PSM. Metformin prescription rather than other antidiabetic medications was related to lower CAC scores (OR [95% CI] = 0.55 [0.34–0.90]; P = 0.018). Further multivariable logistic regression analysis demonstrated that metformin was negatively associated with CAC severity (OR [95% CI] = 0.58 [0.34–0.99]; P = 0.048), which was independent of age, BMI, eGFR, gender, cigarette smoking, duration of diabetes, hypertension, statin prescription, and number of nonmetformin antidiabetic agents. A subgroup analysis revealed a significant association between metformin and CAC scores in smokers (OR [95% CI] = 0.38 [0.16–0.93]; P = 0.035), but the association was not observed in never-smokers (OR [95% CI] = 0.72 [0.34–1.51]; P = 0.383). Conclusions Metformin usage was independently associated with lower CAC scores in T2DM patients. The negative correlation between CAC scores and metformin was most prominent in patients with a history of cigarette smoking.
Detection of mutations in drug resistance genes of Mycobacterium tuberculosis by a dot-blot hybridization strategy.

SETTING Mycobacterium tuberculosis isolates from patients in communities endemic for tuberculosis in South Africa. OBJECTIVE To develop a reliable PCR-based dot-blot hybridization strategy to detect mutations conferring drug resistance. DESIGN Different loci in six genes associated with drug resistance to isoniazid, rifampacin, streptomycin and ethambutol were selected to develop the PCR-based dot-blot hybridization strategy. RESULTS Primers and probes to detect mutations at codons 315, 463 (katG) 269 (kasA), 531, 526 (rpoB) 43 (rpsL), 513 (rrs) and 306 (embB) were designed and used to develop a PCR-based dot-blot hybridization strategy. The dot-blot hybridization strategy with wild-type probes can efficiently be used to detect drug resistant mutations since these do not hybridize to mutant loci. Stripped blots and mutant probes can be used to identify the precise mutation. The embB gene (ethambutol resistance) was used to show how the dot-blot strategy can assist with the prediction of drug resistance more accurately. The method is rapid, reproducible, not technically demanding and samples can be done in batches. Additional loci can easily be incorporated. CONCLUSIONS A PCR-based dot-blot hybridization strategy is described which can accurately identify drug resistant strains and the method is useful for patients at risk and in areas endemic for tuberculosis.
Three Essays on Market and Non-Market Factors Affecting International Seafood Trade

ii Acknowledgement . iv List of Tables . vii List of Figures . viii List of Abbreviations . ix Introduction . 1 Background . 1 Dissertation Outline . 3 References . 6 Chapter 1: Organization of Global Value Chains (GVC) for Shrimp in Vietnam: Food Safety, Socio-Cultural Factors and Material Resource Conditions . 9 Introduction . 9 The GVC Theoretical Framework . 13 Agri-Food Chains. 20 Research Methods . 21 Global Value Chains for Shrimp in Vietnam . 24 Governance of GVC for Shrimp in Vietnam . 31 Discussion and Implications for Food Safety and Socio-Economic Development . 38 Conclusions . 44
Effect of medical education on quality of life in adult asthma patients.

BACKGROUND AND PURPOSE Previous studies revealed that many asthma patients did not understand how to manage their disease, which in turn affected their quality of life. This study investigated the effect of asthma education on quality of life in Taiwanese adults with asthma. METHODS A before and after quasi-experimental design was used. A total of 85 asthma patients were recruited from the asthma clinic of a medical center in northern Taiwan using purposive sampling. Among these patients, 31 were assigned to the experimental group and 54 to the control group. The experimental group received four 1-hour sessions of group education, while the control group received no instruction. Data were collected at 2 different stages: enrollment (baseline), and at 1 month after enrollment. All subjects completed the Asthma Quality of Life Questionnaire and the Asthma General Knowledge Questionnaire for Adults. Data were analyzed using independent-samples t test and paired t test. RESULTS After completing the asthma education sessions, the mean scores on asthma knowledge significantly increased from 19.65 to 23.06 (p < 0.001) in the experimental group. The mean scores for overall quality of life significantly increased from 5.06 to 5.42 (p < 0.01). The mean scores in the symptom domain and the exposure to environmental stimuli domain also significantly increased from 5.07 to 5.46 (p < 0.01) and 4.94 to 5.52 (p < 0.001) after education. However, the mean scores of the control group on the same questionnaire did not change significantly. CONCLUSION Asthma education can significantly improve asthma knowledge and quality of life in adult asthma patients.
Value of Citation Numbers and Impact Factors for Analysis of Plastic Surgery Research

Background: Citations of articles reflect their scientific relevance. The Institute for Scientific Information’s impact factor measures the average number of citations to articles in a journal. Consequently, less-cited articles are credited for the impact that a few frequently cited articles had. Furthermore, the impact factor is only in regard to the citations received in the first 2 years after publication, whereas most articles may be cited only after that period. The authors tested the relevance of the impact factor as a measure of the scientific value of articles. Methods: The authors identified the 10 most-cited articles of four leading journals and calculated the pattern of their citations over the years. On the basis of the most significant change of regression coefficient in this pattern, they established the critical citable period and the number of citations received in the first 2 years as a fraction of the number of citations received during this period. Results: The citation distribution was skewed. The critical citable period was 16 years, in which articles gathered 61.3 percent of their total number of citations (range, 52.3 to 74.3 percent). The number of citations obtained in the first 2 years correlated well with the number of citations received in the critical citable period (Spearman rho = 0.60, p < 0.001), but only 2.5 percent of the latter number was gathered during the first 2 years (range, 1.2 to 4.0 percent). Conclusion: The impact factor is not an adequate indicator for the scientific relevance or impact of the individual articles the authors studied.
Enhanced Cartooning System Based on Dynamic Augmented KMCG and LIP

The Non-Photorealistic Rendering (NPR) demands are increased with the development of electronic devices. This paper presents a new model for a cartooning system, as an essential category of the NPR. It is used the concept of vector quantization and Logarithmic Image Processing (LIP). An enhancement of Kekre Median Codebook Generation (KMCG) algorithm has been proposed and used by the system. Several metrics utilized to evaluate the time and quality of the system. The results showed that the proposed system reduced the time of cartoon production. Additionally, it enhanced the quality of several aspects like smoothing, color reduction, and brightness.
Effects of temperature and salinity on Vibrio cholerae growth

Laboratory microecosystems (microcosms) prepared with a chemically defined sea salt solution were used to study effects of selected environmental parameters on growth and activity of Vibrio cholerae. Growth responses under simulated estuarine conditions of 10 strains of V. cholerae, including clinical and environmental isolates as well as serovars O1 and non-O1, were compared, and all strains yielded populations of approximately the same final size. Effects of salinity and temperature on extended survival of V. cholerae demonstrated that, at an estuarine salinity (25%) and a temperature of 10 degrees C, V. cholerae survived (i.e., was culturable) for less than 4 days. Salinity was also found to influence activity, as measured by uptake of 14C-amino acids. Studies on the effect of selected ions on growth and activity of V. cholerae demonstrated that Na+ was required for growth. The results of this study further support the status of V. cholerae as an estuarine bacterium.
Cyber Threat Intelligence Support to Incident Handling

Recent research has shown increased awareness of Cyber Threat Intelligence (CTI) capabilities. However, CTI teams continue to be underutilized and have had difficulty demonstrating the value they can add to digital forensics incident response (DFIR) teams. Meta-analysis of multiple surveys will identify where the gaps in knowledge exist. The paper will suggest how CTI can support DFIR at each level of intelligence and operations – tactical, operational, and strategic – and during each phase of the incident response lifecycle – preparation; detection and analysis, containment, eradication, and recovery; and lessons learned. CTI teams should have priority intelligence requirements (PIRs) and a collection plan that supports answering those PIRs. In return, DFIR needs to share investigations and incident reports with the CTI team to reduce risk to the organization, decrease the time to detect an incident and decrease the time to remediate an incident. This paper builds on previous work by the author to develop CTI processes to support CTI planning. © 2 01 7 T he SA NS In sti tut e, Au tho r R eta ins Fu ll R igh ts © 2017 The SANS Institute Author retains full rights. Cyber Threat Intelligence Support to Incident Handling 2 Brian P. Kime
Attract-and-kill: a new strategy for the management of the potato tuber moths Phthorimaea operculella (Zeller) and Symmetrischema tangolias (Gyen) in potato: laboratory experiments towards optimising pheromone and insecticide concentration.

BACKGROUND Sex pheromones of the potato tuber moths Phthorimaea operculella (Zeller) and Symmetrischema tangolias (Gyen) are ideal tools to monitor pest flight activity but are not used as means of control. The aim of the present study was to test the suitability of an attract-and-kill strategy consisting of pure pheromones and the contact insecticide cyfluthrin as the active ingredient, formulated with plant oils and ultraviolet absorbers, and applied in droplet sizes of 100 microL. RESULTS Cyfluthrin at a concentration of 5 g L(-1) resulted in the highest and fastest killing of males after 48 h, with a 100% mortality after 3-4 days. In contrast, control males survived for 13 days. In olfactometer experiments, the pheromone concentration of 0.5 g L(-1) was significantly most attractive against eight virgin females. At controlled conditions (20 degrees C), no reduction in efficacy of the attract-and-kill formulation was observed for a minimum period of 36 days, whereas under natural environmental conditions the efficacy reduced gradually after day 6 of exposure. The longer the droplet was exposed, the longer was the time to reach 100% mortality of males. CONCLUSIONS Compared with attract-and-kill studies for other pest species, the results are promising as a means of achieving highly effective control of potato tuber moths under field conditions.
When Does the Ballot Box Limit the Budget? Politics and Spending Limits in California, Colorado, Utah and Washington

Can voters stop governments from spending too much through the enactment of tax and expenditure limits (TELs), or do these laws become dead letters? We examine the effectiveness of TELs - one of the most frequent uses of the initiative process across the country - by viewing them as an attempted solution to a principal-agent problem. Voters are principals who want to constrain the spending habits of their agents, elected officials. Drawing on the lessons of the principal-agent literature yields two insights that structure our study. First, in order to evaluate the effects of TELs, we collect data that provides a comprehensive look at state finances for all 50 states. Our research design departs from much of the recent literature. Rather than simply analyzing state spending levels, we look at changes in combined state and local expenditures, money raised through charges and fees, state debt levels, and state credit ratings. We conduct time series analyses within states that change their fiscal institutions, rather than cross-sectional analyses across states with different rules and fiscal trends. We perform a pre-test by observing a state's fiscal behavior prior to the enactment of a TEL and a post-test by taking observations in the years after the treatment was applied. This allows us to isolate the effect of a TEL while holding other state characteristics constant, thus avoiding the endogeneity problem encountered by much of the previous literature. Our analysis includes an evaluation of whether or not TELs changed state finances as well as a more nuanced consideration of the scale of any such changes. Second, in order to predict which if any TELs will be most effective, we focus less on the letter of the law than on the conditions of its passage. While previous works emphasize the importance of specific legal provisions, we hypothesize that a TEL's success will be determined by the method through which it was passed, the preferences of the lawmakers that it attempts to bind, and the ease of amending the state's constitution.
Meta-analytic evidence for decreased heart rate variability in chronic pain implicating parasympathetic nervous system dysregulation

Abstract Both sympathetic and parasympathetic nervous systems are involved in regulating pain states. The activity of these systems seems to become disturbed in states of chronic pain. This disruption in autonomic balance can be measured through the assessment of heart rate variability (HRV), that is, the variability of the interval between consecutive heart beats. However, there is yet to be a systematic evaluation of the body of literature concerning HRV across several chronic pain conditions. Moreover, modern meta-analytical techniques have never been used to validate and consolidate the extent to which HRV may be decreased in chronic pain. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement guidelines, this study systematically evaluated and critically appraised the literature concerning HRV in people living with chronic pain. After screening 17,350 sources, 51 studies evaluating HRV in a chronic pain group met the inclusion criteria. Twenty-six moderate–high quality studies were included in quantitative meta-analyses. On average, the quality of studies was moderate. There were 6 frequency-domain and time-domain measures of HRV across a broad range of chronic pain conditions. High heterogeneity aside, pooled results from the meta-analyses reflected a consistent, moderate-to-large effect of decreased high-frequency HRV in chronic pain, implicating a decrease in parasympathetic activation. These effects were heavily influenced by fibromyalgia studies. Future research would benefit from wider use of standardised definitions of measurement, and also investigating the synergistic changes in pain state and HRV throughout the development and implementation of mechanism-based treatments for chronic pain.