Miracle-dz/UniFAR-FTUs huggingface dataset:
Selection of Alternative 5′ Splice Sites: Role of U1 snRNP and Models for the Antagonistic Effects of SF2/ASF and hnRNP A1

ABSTRACT The first component known to recognize and discriminate among potential 5′ splice sites (5′SSs) in pre-mRNA is the U1 snRNP. However, the relative levels of U1 snRNP binding to alternative 5′SSs do not necessarily determine the splicing outcome. Strikingly, SF2/ASF, one of the essential SR protein-splicing factors, causes a dose-dependent shift in splicing to a downstream (intron-proximal) site, and yet it increases U1 snRNP binding at upstream and downstream sites simultaneously. We show here that hnRNP A1, which shifts splicing towards an upstream 5′SS, causes reduced U1 snRNP binding at both sites. Nonetheless, the importance of U1 snRNP binding is shown by proportionality between the level of U1 snRNP binding to the downstream site and its use in splicing. With purified components, hnRNP A1 reduces U1 snRNP binding to 5′SSs by binding cooperatively and indiscriminately to the pre-mRNA. Mutations in hnRNP A1 and SF2/ASF show that the opposite effects of the proteins on 5′SS choice are correlated with their effects on U1 snRNP binding. Cross-linking experiments show that SF2/ASF and hnRNP A1 compete to bind pre-mRNA, and we conclude that this competition is the basis of their functional antagonism; SF2/ASF enhances U1 snRNP binding at all 5′SSs, the rise in simultaneous occupancy causing a shift in splicing towards the downstream site, whereas hnRNP A1 interferes with U1 snRNP binding such that 5′SS occupancy is lower and the affinities of U1 snRNP for the individual sites determine the site of splicing.
Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: population study

Abstract Objectives: To investigate whether measles, mumps, and rubella (MMR) vaccination is associated with bowel problems and developmental regression in children with autism, looking for evidence of a “new variant” form of autism. Design: Population study with case note review linked to independently recorded vaccine data. Setting: Five health districts in north east London. Participants: 278 children with core autism and 195 with atypical autism, mainly identified from computerised disability registers and born between 1979 and 1998. Main outcome measures: Recorded bowel problems lasting at least three months, age of reported regression of the child's development where it was a feature, and relation of these to MMR vaccination. Results: The proportion of children with developmental regression (25% overall) or bowel symptoms (17%) did not change significantly (P value for trend 0.50 and 0.47, respectively) during the 20 years from 1979, a period which included the introduction of MMR vaccination in October 1988. No significant difference was found in rates of bowel problems or regression in children who received the MMR vaccine before their parents became concerned about their development (where MMR might have caused or triggered the autism with regression or bowel problem), compared with those who received it only after such concern and those who had not received the MMR vaccine. A possible association between non-specific bowel problems and regression in children with autism was seen but this was unrelated to MMR vaccination. Conclusions: These findings provide no support for an MMR associated “new variant” form of autism with developmental regression and bowel problems, and further evidence against involvement of MMR vaccine in the initiation of autism. What is already known on this topic A “new variant” form of autism has been hypothesised, associated with developmental regression and bowel problems and caused or triggered by the MMR vaccination This postulated association along with media attention has had a major adverse effect on public confidence in the vaccine Although population studies have shown no association between autism and MMR vaccine it has been further postulated that various environmental or genetic cofactors are required for the effect What this study adds The proportion of children with autism who had developmental regression or bowel problems has not changed over the 20 years from 1979 Neither developmental regression nor bowel problems in children with autism was associated with MMR vaccination No evidence was found for a “new variant” form of autism
Biomarkers for rheumatoid arthritis: Making it personal

Abstract Effective treatment of rheumatoid arthritis (RA) has been hampered by the heterogeneity of the disease. Although early intervention can result in disease remission, it requires early diagnosis – and current diagnostic tests are not sufficiently accurate or sensitive in the early stages of RA. As a result, RA is typically diagnosed only once damage to the joints has already begun, a time at which the window for optimal treatment may have been missed. Furthermore, a significant proportion of RA patients do not respond to any given therapeutic. Research efforts are increasingly focused on discovery of biomarkers that enable early diagnosis and stratification of RA, and thus the implementation of timely, targeted therapy. Biomarkers have the potential to transform the management of RA by enabling not only early diagnosis, but also assessment and prediction of disease severity, selection of therapy, and monitoring of response to therapy. In this mini review, we discuss the development of molecular biomarkers for RA.
The Role of Peroxidases in the Activation of Chemical Carcinogens

Peroxidases exhibit a wide substrate specificity with respect to various carcinogenic xenobiotics. Peroxidase-mediated activations of several carcinogenic polycyclic aromatic hydrocarbons, aromatic amines, phenols, azo dyes and N-nitrosamines are reviewed, considering their possible involvement in the initiation of chemical carcinogenesis. Activation pathways of these carcinogens examined in vitro, in subcellular fractions, cell cultures and in vivo are evaluated.
A spatio-temporal approach to collaborative filtering

In this paper, we propose a novel spatio-temporal model for collaborative filtering applications. Our model is based on low-rank matrix factorization that uses a spatio-temporal filtering approach to estimate user and item factors. The spatial component regularizes the factors by exploiting correlation across users and/or items, modeled as a function of some implicit feedback (e.g., who rated what) and/or some side information (e.g., user demographics, browsing history). In particular, we incorporate correlation in factors through a Markov random field prior in a probabilistic framework, whereby the neighborhood weights are functions of user and item covariates. The temporal component ensures that the user/item factors adapt to process changes that occur through time and is implemented in a state space framework with fast estimation through Kalman filtering. Our spatio-temporal filtering (ST-KF hereafter) approach provides a single joint model to simultaneously incorporate both spatial and temporal structure in ratings and therefore provides an accurate method to predict future ratings. To ensure scalability of ST-KF, we employ a mean-field approximation for inference. Incorporating user/item covariates in estimating neighborhood weights also helps in dealing with both cold-start and warm-start problems seamlessly in a single unified modeling framework; covariates predict factors for new users and items through the neighborhood. We illustrate our method on simulated data, benchmark data and data obtained from a relatively new recommender system application arising in the context of Yahoo! Front Page.
Supporting Materials : Photon shot noise limits on optical detection of neuronal spikes and estimation of spike timing

a linear combination of the Poisson-distributed variables, fn. We rewrite the log-likelihood ratio in terms of sn ≡ (A/F0) τν ( e − 1 ) e−n/(τν). Most calculations in this paper rely on taking series approximations in sn and performing the summations to leading order. This approach is valid as long as A < F0, since τν ( e − 1 ) e−n/(τν) is bounded above by 1 for n ≥ 1, and the interval of convergence for the series expansion of log (1 + x) is −1 < x ≤ 1. The mean, μ, and variance, σ, of the distribution of L(f) under the null hypothesis H of no spike having occurred are given by
On the positive and negative effects of self-efficacy on performance: Reward as a moderator

ABSTRACT We address the controversy regarding the sign of the effect of self-efficacy on performance. We propose that when reward is high, self-efficacy has a positive effect on performance, whereas when reward is low, it has a negative effect. This hypothesis was tested in three experiments (with sample sizes of 76, 99, and 111) in which reward and self-efficacy were manipulated and performance was measured using different manipulations and tasks in both within-factor and between-factor designs. The results supported the hypothesis that reward moderates the effect of self-efficacy on performance. When reward was high, the effect of self-efficacy on performance was positive, whereas when reward was low, the effect of self-efficacy on performance was negative.
Third-generation sequencing and the future of genomics

Third-generation long-range DNA sequencing and mapping technologies are creating a renaissance in high-quality genome sequencing. Unlike second-generation sequencing, which produces short reads a few hundred base-pairs long, third-generation single-molecule technologies generate over 10,000 bp reads or map over 100,000 bp molecules. We analyze how increased read lengths can be used to address longstanding problems in de novo genome assembly, structural variation analysis and haplotype phasing.
Quinolone‐Resistant Neisseria gonorrhoeae: The Beginning of the End?: Report of Quinolone‐Resistant Isolates and Surveillance in the Southwestern United States, 1989 to 1997

Background: Fluoroquinolones are one of the most widely used treatments for gonorrhoeae. Changes in the susceptibility of Neisseria gonorrhoeae to these agents may threaten their use. Goal of this study: To report several resistant strains (>1 mcg/ml) isolated in the western United States and to evaluate the prevalence of strains with reduced susceptibility (ofloxacin 0.25 mcg/ml, ciprofloxacin 0.06 mcg/ml). Study Design: The microbiology and epidemiology of three resistant strains were characterized and 12,761 other strains were evaluated for fluoroquinolone susceptibility as part of the Gonococcal Isolate Surveillance Project of the Centers for Disease Control and Prevention. Results: Fluoroquinolone‐resistant strains may appear sporadically. The prevalence of isolates with reduced susceptibility to fluoroquinolones remains low in the Southwest region of the United States. Conclusions: Continued active surveillance is needed to detect and control the spread of quinolone‐resistant Neisseria gonorrhoeae.
Phytochemical characterisation of green beans (Phaseolus vulgaris L.) by using high-performance liquid chromatography coupled with time-of-flight mass spectrometry.

INTRODUCTION Although green beans (Phaseolus vulgaris L.) constitute a major agro-industrial crop worldwide and involve many bean varieties, the phytochemical composition and how this fluctuates among varieties is not well known. OBJECTIVE The purpose of this work was to conduct a comprehensive characterisation of the phytochemical compounds found in three varieties of green bean. METHODOLOGY Hydromethanol extracts from green beans were analysed by high-performance liquid chromatography (HPLC) coupled with electrospray time-of-flight mass spectrometry (ESI-TOF-MS) in order to characterise phytochemical compounds from different varieties of P. vulgaris L. The compounds were characterised based on interpreting their mass spectrum provided by the TOF-MS as well as by comparison with information from the literature (some compounds have been described previously in Fabaceae). RESULTS In this work, 72 phytochemical compounds were tentatively characterised by HPLC-ESI-TOF-MS. These compounds were classified as, 10 phenolic acids, 59 flavonoids, two lignans and an iridoid. Notably, out of the 72 compounds, 54 are new and their isomers have been characterised for the first time in green beans. CONCLUSION The phytochemical composition of three different varieties of P. vulgaris L have been characterised using HPLC-ESI-TOF-MS. A total of 72 phytochemical compounds were characterised, 54 being reported in green beans for the first time. Among these were the main flavonoids detected. These results highlight the influence that variety can exert on the quality of phytochemicals. Given that new phytochemical compounds have been characterised, this study offers a useful approach for improving and updating the food-composition tables.
Applications of graph containers in the Boolean lattice

We apply the graph container method to prove a number of counting results for the Boolean lattice P(n) . In particular, we: Give a partial answer to a question of Sapozhenko estimating the number of t error correcting codes in P(n) , and we also give an upper bound on the number of transportation codes; Provide an alternative proof of Kleitman's theorem on the number of antichains in P(n) and give a two‐coloured analogue; Give an asymptotic formula for the number of (p, q)‐tilted Sperner families in P(n) ; Prove a random version of Katona's t‐intersection theorem. In each case, to apply the container method, we first prove corresponding supersaturation results. We also give a construction which disproves two conjectures of Ilinca and Kahn on maximal independent sets and antichains in the Boolean lattice. A number of open questions are also given. © 2016 Wiley Periodicals, Inc. Random Struct. Alg. , 49, 845–872, 2016
An approach for mapping large-area impervious surfaces: synergistic use of Landsat-7 ETM+ and high spatial resolution imagery

A wide range of urban ecosystem studies, including urban hydrology, urban climate, land use planning, and resource management, require current and accurate geospatial data of urban impervious surfaces. We developed an approach to quantify urban impervious surfaces as a continuous variable by using multisensor and multisource datasets. Subpixel percent impervious surfaces at 30-m resolution were mapped using a regression tree model. The utility, practicality, and affordability of the proposed method for large-area imperviousness mapping were tested over three spatial scales (Sioux Falls, South Dakota, Richmond, Virginia, and the Chesapeake Bay areas of the United States). Average error of predicted versus actual percent impervious surface ranged from 8.8 to 11.4%, with correlation coefficients from 0.82 to 0.91. The approach is being implemented to map impervious surfaces for the entire United States as one of the major components of the circa 2000 national land cover database.
Combined Adipocyte-Macrophage Fatty Acid–Binding Protein Deficiency Improves Metabolism, Atherosclerosis, and Survival in Apolipoprotein E–Deficient Mice

Background—The adipocyte fatty acid–binding protein (FABP) aP2 is expressed by adipocytes and macrophages and modulates insulin resistance, glucose and lipid metabolism, and atherosclerosis. Insulin sensitivity is improved in obese but not in lean aP2-deficient mice. A second fatty acid–binding protein, mal1, also is expressed in adipocytes and macrophages, and mal1 deficiency produces similar effects on insulin resistance. We tested the hypothesis that combined aP2 and mal1 deficiency would produce synergistic effects on metabolism and reduce atherosclerosis in apolipoprotein E–deficient (apoE−/−) mice. Methods and Results—Male and female apoE−/− mice null for both aP2 and mal1 (3KO) and apoE−/− controls were fed a low-fat chow diet for 16 or 56 weeks. Lean 3KO mice had significantly lower serum cholesterol and triglycerides as well as improved insulin and glucose tolerance as compared with controls. Analysis of atherosclerotic lesions in the 3KO mice showed dramatic reductions in both early (20 weeks) and late-stage (60 weeks) atherosclerosis. Strikingly, survival in the 3KO mice was improved by 67% as compared with apoE−/− controls when challenged with the Western diet for 1 year. Conclusions—Combined aP2 and mal1 deficiency improved glucose and lipid metabolism, reduced atherosclerosis, and improved survival in apoE−/− mice, making these proteins important therapeutic targets for the prevention of the cardiovascular consequences of the metabolic syndrome.
‘It's different, but it's the same’: perspectives of young adults with siblings with intellectual disabilities in residential care

Accessible summary Siblings often play important roles in the lives of people with intellectual disabilities. This study suggests that young adults who have siblings in residential care can feel isolated in their experience. Adolescence appears to be a turning point and a time when siblings become aware of future caretaking responsibilities. There is a need for support for siblings of children and adults with intellectual disabilities who live in residential care. Abstract Background: Siblings often play significant roles in the lives of people with intellectual disabilities. This study aimed to give voice to young adults whose siblings have an intellectual disability and are in residential care. Materials and Methods: Six participants were interviewed, with interpretative phenomenological analysis methodology employed. Results: Emergent themes included family and sibling relationships and concerns for the future. However, ambivalence, in terms of conflicting feelings within participants themselves, was striking. Dissonances within narratives included identifying as ‘one family’ whilst living apart, experiencing guilt while being supportive of the residential placement, and emphasising the normality of the sibling experience whilst also feeling different and isolated. Conclusion: These findings reflect the particular complexity of sibling relationships when the person with an intellectual disability lives in residential care. There is a need to understand more about the perspectives of siblings, and the influence that residential care may have upon these.
Global Warming and Its Health Impact

Since the mid-19th century, human activities have increased greenhouse gases such as carbon dioxide, methane, and nitrous oxide in the Earth's atmosphere that resulted in increased average temperature. The effects of rising temperature include soil degradation, loss of productivity of agricultural land, desertification, loss of biodiversity, degradation of ecosystems, reduced fresh-water resources, acidification of the oceans, and the disruption and depletion of stratospheric ozone. All these have an impact on human health, causing non-communicable diseases such as injuries during natural disasters, malnutrition during famine, and increased mortality during heat waves due to complications in chronically ill patients. Direct exposure to natural disasters has also an impact on mental health and, although too complex to be quantified, a link has even been established between climate and civil violence. Over time, climate change can reduce agricultural resources through reduced availability of water, alterations and shrinking arable land, increased pollution, accumulation of toxic substances in the food chain, and creation of habitats suitable to the transmission of human and animal pathogens. People living in low-income countries are particularly vulnerable. Climate change scenarios include a change in distribution of infectious diseases with warming and changes in outbreaks associated with weather extreme events. After floods, increased cases of leptospirosis, campylobacter infections and cryptosporidiosis are reported. Global warming affects water heating, rising the transmission of water-borne pathogens. Pathogens transmitted by vectors are particularly sensitive to climate change because they spend a good part of their life cycle in a cold-blooded host invertebrate whose temperature is similar to the environment. A warmer climate presents more favorable conditions for the survival and the completion of the life cycle of the vector, going as far as to speed it up as in the case of mosquitoes. Diseases transmitted by mosquitoes include some of the most widespread worldwide illnesses such as malaria and viral diseases. Tick-borne diseases have increased in the past years in cold regions, because rising temperatures accelerate the cycle of development, the production of eggs, and the density and distribution of the tick population. The areas of presence of ticks and diseases that they can transmit have increased, both in terms of geographical extension than in altitude. In the next years the engagement of the health sector would be working to develop prevention and adaptation programs in order to reduce the costs and burden of climate change.
[Hodgkin's disease].

Epidemiology of Hodgkin's disease pathophysiology of Hodgkin's disease - functional and molecular aspects immunology of Hodgkin's disease pathology and molecular histology of Hodgkin's disease and the border to non-Hodgkin lymphomas diagnostic procedures historical perspective and clinical presentation management of early stage Hodgkin's disease - the role of radiation therapy and/or chemotherapy treatment or Hodgkin's disease - the role of radiation therapy and/or chemotherapy in the intermediate stages treatment of Hodgkin's disease - the role of radiation therapy and/or chemotherapy in advanced stages treatment of relapsed Hodgkin's disease future treatment strategies - fact or fiction? treatment sequelae and quailty of life new antigens in Hodgkin's disease Hodgkin's disease in children.
Challenges in the Assembly and Handling of Thin Film Capped MEMS Devices

This paper discusses the assembly challenges considering the design and manufacturability of a Wafer Level Thin Film Package in MEMS applications. The assembly processes are discussed. The loads associated with these processes are illustrated and evaluated. Numerical calculations are combined with experimental observations in order to estimate the assembly risks. Our results emphasize the need for concurrent design for assembly.
Limits to captive breeding of mammals in zoos

Captive breeding of mammals in zoos is the last hope for many of the best‐known endangered species and has succeeded in saving some from certain extinction. However, the number of managed species selected is relatively small and focused on large‐bodied, charismatic mammals that are not necessarily under strong threat and not always good candidates for reintroduction into the wild. Two interrelated and more fundamental questions go unanswered: have the major breeding programs succeeded at the basic level of maintaining and expanding populations, and is there room to expand them? I used published counts of births and deaths from 1970 to 2011 to quantify rates of growth of 118 captive‐bred mammalian populations. These rates did not vary with body mass, contrary to strong predictions made in the ecological literature. Most of the larger managed mammalian populations expanded consistently and very few programs failed. However, growth rates have declined dramatically. The decline was predicted by changes in the ratio of the number of individuals within programs to the number of mammal populations held in major zoos. Rates decreased as the ratio of individuals in programs to populations increased. In other words, most of the programs that could exist already do exist. It therefore appears that debates over the general need for captive‐breeding programs and the best selection of species are moot. Only a concerted effort could create room to manage a substantially larger number of endangered mammals.