Miracle-dz/UniFAR-FTUs huggingface dataset:
Societal costs of underage drinking.

OBJECTIVE Despite minimum-purchase-age laws, young people regularly drink alcohol. This study estimated the magnitude and costs of problems resulting from underage drinking by category-traffic crashes, violence, property crime, suicide, burns, drownings, fetal alcohol syndrome, high-risk sex, poisonings, psychoses, and dependency treatment-and compared those costs with associated alcohol sales. Previous studies did not break out costs of alcohol problems by age. METHOD For each category of alcohol-related problems, we estimated fatal and nonfatal cases attributable to underage alcohol use. We multiplied alcohol-attributable cases by estimated costs per case to obtain total costs for each problem. RESULTS Underage drinking accounted for at least 16% of alcohol sales in 2001. It led to 3,170 deaths and 2.6 million other harmful events. The estimated $61.9 billion bill (relative SE = 18.5%) included $5.4 billion in medical costs, $14.9 billion in work loss and other resource costs, and $41.6 billion in lost quality of life. Quality-of-life costs, which accounted for 67% of total costs, required challenging indirect measurement. Alcohol-attributable violence and traffic crashes dominated the costs. Leaving aside quality of life, the societal harm of $1 per drink consumed by an underage drinker exceeded the average purchase price of $0.90 or the associated $0.10 in tax revenues. CONCLUSIONS Recent attention has focused on problems resulting from youth use of illicit drugs and tobacco. In light of the associated substantial injuries, deaths, and high costs to society, youth drinking behaviors merit the same kind of serious attention.
The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase

Objective The present study intended to investigate whether the impaired H2S synthase/H2S pathway is associated with hypertension. Methods Hypertension in Wistar rats was induced by the oral administration of the l-arginine analog, NG-nitro-l-arginine methyl ester (l-NAME) in their drinking water for a period of 6 weeks. The control rats were given plain tap water only. Sodium hydrosulfide (NaHS) was given by intraperitoneal injection to both the control group and the l-NAME-treated group. The systolic BP (blood pressure) was measured by a tail-cuff method using a pulse transducer. Plasma hydrogen sulfide (H2S), and H2S generation by thoracic aorta and superior mesenteric artery, were determined. In addition, the activity of cystathionine-γ-lyase (CSE) in thoracic aorta and superior mesenteric artery, most responsible for H2S production, was also measured. Competitive reverse transcriptase–polymerase chain reaction (RT-PCR) was used to determine CSE mRNA in thoracic aorta. Results l-NAME caused a time-dependent elevation of systolic BP. The heart-to-body weight ratio of l-NAME-treated rats was 27% higher than that of controls. The systolic BP in the NaHS-treated l-NAME group was significantly decreased, by 19% (P < 0.01), in comparison with the l-NAME group. The heart-to-body weight ratio decreased significantly by 12%. l-NAME inhibited CSE gene expression significantly. The inhibition of H2S generation and CSE activity by l-NAME was greatly attenuated in the NaHS-treated l-NAME group. However, there was no significant difference in nitric oxide (NO) generation between the l-NAME group and the NaHS-treated l-NAME group. Conclusion In summary, dysfunction of the vascular H2S synthase/H2S pathway was found in l-NAME-induced hypertensive rats. Exogenous H2S effectively prevented the development of hypertension induced by l-NAME. These findings suggest that the H2S synthase/H2S pathway participates in hypertension.
Importance of the El Niño Teleconnection to the 21st Century California Wintertime Extreme Precipitation Increase

Under continued climate warming, California (CA) hydrological projections, particularly precipitation, exhibit significant uncertainty. Recent analyses, however, have indicated a tendency for increased CA precipitation through the 21st century, particularly during December‐January‐February (DJF). Here we show that this increase is due entirely to an increase in extreme (>90th percentile) daily precipitation. This response is consistent with enhanced horizontal vapor transport off the CA coast, most of which is caused by thermodynamical effects due to increases in atmospheric moisture. Furthermore, observations over the late twentieth century show that CA DJF extreme precipitation is associated with an El Niño‐like sea surface temperature anomaly pattern. Models that better simulate the observed El Niño teleconnection with CA DJF precipitation also better reproduce the El Niño‐like sea surface temperature anomaly pattern associated with extreme precipitation, including the associated thermodynamical and dynamical atmospheric responses. In turn, these models simulate a significantly larger increase in extreme precipitation under warming.
Calibration of the dietary questionnaire for the Canadian Study of Diet, Lifestyle and Health cohort

Abstract Objective: For proper interpretation of results from epidemiological studies that use food-frequency questionnaires (FFQs), it is necessary to know the relationship between reported intakes from the FFQ and true usual intake. In this paper, we report a calibration study conducted to investigate the performance of the FFQ used in a cohort study, the Canadian Study of Diet, Lifestyle and Health. Methods: Over a 1-year period, 151 men and 159 women completed a full set of questionnaires including a self-administered baseline FFQ, three 24-hour diet recalls administered by telephone, and a second FFQ self-administered subsequently. The association between the nutrient estimates derived from the FFQs and the diet recalls was evaluated by calculating deattenuated Pearson's correlation coefficients. Results: The FFQs estimated mean daily nutrient intakes higher than the diet recalls. When the log-transformed and energy-adjusted nutrient intakes from the average of three 24-hour recalls were compared against the baseline FFQ, the following deattenuated correlations were obtained in men and women, respectively: total energy 0.44 and 0.32, total fat 0.64 and 0.68, saturated fat 0.68 and 0.70, dietary fibre 0.65 and 0.44, vitamin E 0.32 and 0.37, vitamin C 0.40 and 0.37, β-carotene 0.34 and 0.29, alcohol 0.74 and 0.67, caffeine 0.81 and 0.76, with a median correlation of 0.49 and 0.53. Correlations between the second FFQ and diet recalls were similar. The correlations between the two FFQs as a test of reliability had a median value 0.64 for men and 0.63 for women for selected nutrients. Conclusions: The study suggests that the FFQ method gives acceptable levels of nutrients or food component estimates, as assessed by this calibration study against diet recalls, when limited to energy-adjusted and deattenuated values.
Requirement for highly efficient pre-mRNA splicing during Drosophila early embryonic development

Drosophila syncytial nuclear divisions limit transcription unit size of early zygotic genes. As mitosis inhibits not only transcription, but also pre-mRNA splicing, we reasoned that constraints on splicing were likely to exist in the early embryo, being splicing avoidance a possible explanation why most early zygotic genes are intronless. We isolated two mutant alleles for a subunit of the NTC/Prp19 complexes, which specifically impaired pre-mRNA splicing of early zygotic but not maternally encoded transcripts. We hypothesized that the requirements for pre-mRNA splicing efficiency were likely to vary during development. Ectopic maternal expression of an early zygotic pre-mRNA was sufficient to suppress its splicing defects in the mutant background. Furthermore, a small early zygotic transcript with multiple introns was poorly spliced in wild-type embryos. Our findings demonstrate for the first time the existence of a developmental pre-requisite for highly efficient splicing during Drosophila early embryonic development and suggest in highly proliferative tissues a need for coordination between cell cycle and gene architecture to ensure correct gene expression and avoid abnormally processed transcripts. DOI: http://dx.doi. org/10.7554/eLife.02181. 001
Mutations in the Res subunit of the EcoPI restriction enzyme that affect ATP-dependent reactions.

The Res subunits of the type III restriction-modification enzymes share a statistically significant amino acid sequence similarity with several RNA and DNA helicases of the so-called DEAD family. It was postulated that in type III restriction enzymes a DNA helicase activity may be required for local unwinding at the cleavage site. The members of this family share seven conserved motifs, all of which are found in the Res subunit of the type III restriction enzymes. To determine the contribution, if any, of these motifs in DNA cleavage by EcoPI, a type III restriction enzyme, we have made changes in motifs I and II. While mutations in motif I (GTGKT) clearly affected ATP hydrolysis and resulted in loss of DNA cleavage activity, mutation in motif II (DEPH) significantly decreased ATP hydrolysis but had no effect on DNA cleavage. The double mutant R.EcoPIK90R-H229K showed no significant ATPase or DNA restriction activity though ATP binding was not affected. These results imply that there are at least two ATPase reaction centres in EcoPI restriction enzyme. Motif I appears to be involved in coupling DNA restriction to ATP hydrolysis. Our results indicate that EcoPI restriction enzyme does not have a strand separation activity. We suggest that these motifs play a role in the ATP-dependent translocation that has been proposed to occur in the type III restriction enzymes.
PipeRench: a coprocessor for streaming multimedia acceleration

Future computing workloads will emphasize an architecture's ability to perform relatively simple calculations on massive quantities of mixed-width data. This paper describes a novel reconfigurable fabric architecture, PipeRench, optimized to accelerate these types of computations. PipeRench enables fast, robust compilers, supports forward compatibility, and virtualizes configurations, thus removing the fixed size constraint present in other fabrics. For the first time we explore how the bit-width of processing elements affects performance and show how the PipeRench architecture has been optimized to balance the needs of the compiler against the realities of silicon. Finally, we demonstrate extreme performance speedup on certain computing kernels (up to 190x versus a modern RISC processor), and analyze how this acceleration translates to application speedup.
The spread of industry: spatial agglomeration in economic development

This paper describes the spread of industry from country to country as a region grows. All industrial sectors are initially agglomerated in one country, tied together by input-output links between firms. Growth expands industry more than other sectors, bidding up wages in the country in which industry is clustered. At some point some firms start to move away, and when a critical mass is reached industry expands in another country, raising wages there. We establish the circumstance sin which industry spill over, which sectors move out first, and which are more important in triggering a critical mass.
Does Astronomical and Geographical Information of Plutarch's De Facie Describe a Trip Beyond the North Atlantic Ocean?

ABSTRACT Liritzis, I. ; Preka-Papadema, P.; Antonopoulos, P.; Kalachanis, K. , and Tzanis, C.G. , 2018. Does astronomical and geographical information of Plutarch's De Facie describe a trip beyond the North Atlantic Ocean? In Plutarch's book On the Apparent Face in the Orb of the Moon, the interlocutors develop a dialogue about a trip to the “great continent” beyond the North Atlantic Ocean. By applying modern scientific data, the present reappraisal of the astronomical and geographical elements within this dialogue has produced a novel interpretation of the date and place of the meeting and a journey to the northern Atlantic Ocean. A described solar eclipse is dated to AD 75, making use of the National Aeronautics and Space Administration (NASA)/Espenak/Meeus list, as well as historical information. The described peculiar, recurrent trips take place every 30 years (when the planet Saturn reaches the Taurus constellation) from the Mediterranean Sea to the Cronian Open Sea, which is identified with northern Atlantic Ocean coasts. It has been suggested that the last mission had returned homeland in April AD 56. The information provided concerns, distances between coastal sites and islands, duration of sea paths in days, and the reported setting and size between the destination place and its gulf with regards to Azov (in Crimea) and the Caspian Sea. Implications of sea currents and the coastal geomorphology of those lands are given. Following strictly the Gulf Stream current, as well as other known sea currents in the northern Atlantic Ocean, and introducing estimated speed for the ship, the geographical location of destination of the Greek settlers is proposedly identified with St. Lawrence Gulf and Newfoundland island. Other unnamed islands mentioned in this dialogue are identified with Norway's islands, Azores, Iceland, Greenland, and Baffin islands. It has been shown that the journey is made with good knowledge of sea currents but by using bright stars and stellar configurations as astronomical nightscape markers that determine the exact orientation of the sailing toward the Iberian Peninsula and back to the eastern Mediterranean, making the current working hypothesis a plausible event.
NBER WORKING PAPER SERIES INVESTMENT UNDER UNCERTAINTY AND THE VALUE OF REAL AND FINANCIAL FLEXIBILITY

We thank Ilona Babenka, Martin Cherkes, Sudipto Dasgupta, Peter DeMarzo, Dirk Hackbarth, Mark Gertler, Simon Gilchrist, Vicky Henderson, Erica Xuenan Li, and seminar participants at American Finance Association (AFA) 2014 meetings in Philadelphia, Boston University, China International Conference in Finance (CICF), Columbia University, HKUST 2013 Finance Symposium, Rutgers University, University of Cambridge, University of Minnesota Carlson School, and Zhejiang University for helpful comments. The views expressed herein are those of the authors and do not necessarily reflect the views of the National Bureau of Economic Research.
Development of siRNA payloads to target KRAS-mutant cancer.

UNLABELLED RNAi is a powerful tool for target identification and can lead to novel therapies for pharmacologically intractable targets such as KRAS. RNAi therapy must combine potent siRNA payloads with reliable in vivo delivery for efficient target inhibition. We used a functional "Sensor" assay to establish a library of potent siRNAs against RAS pathway genes and to show that they efficiently suppress their targets at low dose. This reduces off-target effects and enables combination gene knockdown. We administered Sensor siRNAs in vitro and in vivo and validated the delivery of KRAS siRNA alone and siRNA targeting the complete RAF effector node (A/B/CRAF) as promising strategies to treat KRAS-mutant colorectal cancer. We further demonstrate that improved therapeutic efficacy is achieved by formulating siRNA payloads that combine both single-gene siRNA and node-targeted siRNAs (KRAS + PIK3CA/B). The customizable nature of Sensor siRNA payloads offers a universal platform for the combination target identification and development of RNAi therapeutics. SIGNIFICANCE To advance RNAi therapy for KRAS-mutant cancer, we developed a validated siRNA library against RAS pathway genes that enables combination gene silencing. Using an in vivo model for real-time siRNA delivery tracking, we show that siRNA-mediated inhibition of KRAS as well as RAF or PI3K combinations can impair KRAS-mutant colorectal cancer in xenograft models.
Distracted in a Demanding Task: A Classification Study with Artificial Neural Networks

An important issue in cognitive science research is to know what your subjects are thinking about. In this paper, we trained multiple artificial Neural Network (ANN) classifiers to predict whether subjects’ thoughts were focused on the task (i.e., on-task) or if they were distracted (i.e., distracted thought), based on recorded eye-tracking features and task performance. Novel in this study is that we used data from a demanding spatial complex working memory task. The results of this study showed that we could classify on-task vs. distracted thought with an average of 60% accuracy. Task performance was found to be the strongest predictor of distracted thought. Eye-tracking features (e.g., pupil size, blink duration, fixation duration) were found to be much less predictive. Recent literature showed potential for eye-tracking features, but this study suggests that the nature of the task can greatly affect this potential. Rehearsal effort based on eye-movement behavior was found to be the most promising eye-tracking feature. Although speculative, we argue that eye-movement features are independent of the content of distracted thought and may therefore provide a more generic feature for classifying distracted thought.
Spatiometabolic Stratification of Shewanella oneidensis Biofilms

ABSTRACT Biofilms, or surface-attached microbial communities, are both ubiquitous and resilient in the environment. Although much is known about how biofilms form, develop, and detach, very little is understood about how these events are related to metabolism and its dynamics. It is commonly thought that large subpopulations of cells within biofilms are not actively producing proteins or generating energy and are therefore dead. An alternative hypothesis is that within the growth-inactive domains of biofilms, significant populations of living cells persist and retain the capacity to dynamically regulate their metabolism. To test this, we employed unstable fluorescent reporters to measure growth activity and protein synthesis in vivo over the course of biofilm development and created a quantitative routine to compare domains of activity in independently grown biofilms. Here we report that Shewanella oneidensis biofilm structures reproducibly stratify with respect to growth activity and metabolism as a function of size. Within domains of growth-inactive cells, genes typically upregulated under anaerobic conditions are expressed well after growth has ceased. These findings reveal that, far from being dead, the majority of cells in mature S. oneidensis biofilms have actively turned-on metabolic programs appropriate to their local microenvironment and developmental stage.
A theory of bisimulation for a fragment of Concurrent ML with local names

Concurrent ML is an extension of Standard ML with /spl pi/-calculus-like primitives for multi-threaded programming. CML has a reduction semantics, but to date there has been no labelled transitions semantics provided for the entire language. We present a labelled transition semantics for a fragment of CML called /spl mu/vCML which includes features not covered before: dynamically generated local channels and thread identifiers. We show that weak bisimulation for /spl mu/vCML is a congruence, and coincides with barbed bisimulation congruence. We also provide a variant of D. Sangiorgi's (1993) normal bisimulation for /spl mu/vCML, and show that this too coincides with bisimulation.
Recurrent floods and prevalence of diarrhea among under five children: observations from Bahraich district, Uttar Pradesh, India

Background : Diarrhea is an important problem among the under-five children in India. Objective : The paper examines long-term impacts of recurrent floods on diarrhea among under-five children in Uttar Pradesh, India. Design : A two stage stratified cluster survey was conducted in flood affected (exposed) and non-flood affected areas (unexposed). Results : The long-term impact of the floods was not clearly marked in the overall prevalence of diarrhea with the exposed group having prevalence of 55.1% as against 56.2% in the unexposed group of children under five. Economic condition of the household is associated with the prevalence of diarrhea in both exposed and unexposed strata. Anemia was found to be a significant risk factor for diarrhea among children in both the flood exposed and non-flood exposed populations. The recurrent floods did not have any significant effect on the prevalence of diarrhea in relation to gender, religion, caste, and household size. Conclusions : The study indicates that the long-term impacts of floods are very differently manifested than the immediate impacts.
Benefits of a gluten-free diet for asymptomatic patients with serologic markers of celiac disease.

BACKGROUND & AIMS We investigated whether screen-detected and apparently asymptomatic adults with endomysial antibodies (EmA) benefit from a gluten-free diet (GFD). METHODS We performed a prospective trial of 3031 individuals at risk for celiac disease based on screens for EmA. Of 148 seropositive individuals, 40 fulfilled inclusion criteria and were assigned randomly to groups placed on a GFD or gluten-containing diets. We evaluated ratios of small-bowel mucosal villous height:crypt depth, serology and laboratory test results, gastrointestinal symptom scores, physiologic well-being, perception of health by a visual analog scale, bone mineral density, and body composition at baseline and after 1 year. Thereafter, the group on the gluten-containing diet started a GFD and was evaluated a third time; subjects in the GFD group remained on this diet. RESULTS After 1 year on the GFD, the mean mucosal villous height:crypt depth values increased (P < .001), levels of celiac-associated antibodies decreased (P < .003), and gastrointestinal symptoms improved to a greater extent than in patients on gluten-containing diets (P = .003). The GFD group also had reduced indigestion (P = .006), reflux (P = .05), and anxiety (P = .025), and better health, based on the visual analog scale (P = .017), than the gluten-containing diet group. Only social function scores improved more in the gluten-containing diet group than in the GFD group (P = .031). There were no differences between groups in laboratory test results, bone mineral density, or body composition. Most measured parameters improved when patients in the gluten-containing diet group were placed on GFDs. No subjects considered their experience to be negative and most expected to remain on GFDs. CONCLUSIONS GFDs benefit asymptomatic EmA-positive patients. The results support active screening of patients at risk for celiac disease. Clinicaltrials.gov no: NCT01116505.
Effects of sporulation pH on the heat resistance and the sporulation of Bacillus cereus

Spores of Bacillus cereus ATCC 7004, 4342 and 9818 were obtained in nutrient agar at several pH from 5·9 to 8·3. The optimum pH for sporulation was around 7, but good production of spores was obtained in the range 6·5–8·3. With all three strains, D‐values clearly dropped with sporulation pH, decreasing by about 65% per pH unit. z‐Values were not significantly modified (P > 0·05) by this factor. Mean z‐values of 7·13 °C ± 0·16 for strain 7004, 7·67 °C ± 0·04 for 4342 and 8·80 °C ± 0·64 for 9818 were obtained.