Confluent Orthogonal Drawings of Syntax Diagrams

We provide a pipeline for generating syntax diagrams (also called railroad diagrams) from context free grammars. Syntax diagrams are a graphical representation of a context free language, which we formalize abstractly as a set of mutually recursive nondeterministic finite automata and draw by combining elements from the confluent drawing, layered drawing, and smooth orthogonal drawing styles. Within our pipeline we introduce several heuristics that modify the grammar but preserve the language, improving the aesthetics of the final drawing.Comment: GD 201

New insights into atypical Alzheimer's disease in the era of biomarkers

Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. In the past, these individuals often received a late diagnosis; however, availability of CSF and PET biomarkers of Alzheimer's disease pathologies and incorporation of atypical forms of Alzheimer's disease into new diagnostic criteria increasingly allows them to be more confidently diagnosed early in their illness. This early diagnosis in turn allows patients to be offered tailored information, appropriate care and support, and individualised treatment plans. These advances will provide improved access to clinical trials, which often exclude atypical phenotypes. Research into atypical Alzheimer's disease has revealed previously unrecognised neuropathological heterogeneity across the Alzheimer's disease spectrum. Neuroimaging, genetic, biomarker, and basic science studies are providing key insights into the factors that might drive selective vulnerability of differing brain networks, with potential mechanistic implications for understanding typical late-onset Alzheimer's disease

Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

Biomimetic Synthesis of Gelatin Polypeptide-Assisted Noble-Metal Nanoparticles and Their Interaction Study

Herein, the generation of gold, silver, and silver–gold (Ag–Au) bimetallic nanoparticles was carried out in collagen (gelatin) solution. It first showed that the major ingredient in gelatin polypeptide, glutamic acid, acted as reducing agent to biomimetically synthesize noble metal nanoparticles at 80°C. The size of nanoparticles can be controlled not only by the mass ratio of gelatin to gold ion but also by pH of gelatin solution. Interaction between noble-metal nanoparticles and polypeptide has been investigated by TEM, UV–visible, fluorescence spectroscopy, and HNMR. This study testified that the degradation of gelatin protein could not alter the morphology of nanoparticles, but it made nanoparticles aggregated clusters array (opposing three-dimensional α-helix folding structure) into isolated nanoparticles stabilized by gelatin residues. This is a promising merit of gelatin to apply in the synthesis of nanoparticles. Therefore, gelatin protein is an excellent template for biomimetic synthesis of noble metal/bimetallic nanoparticle growth to form nanometer-sized device

XSTREAM: A practical algorithm for identification and architecture modeling of tandem repeats in protein sequences

<p>Abstract</p> <p>Background</p> <p>Biological sequence repeats arranged in tandem patterns are widespread in DNA and proteins. While many software tools have been designed to detect DNA tandem repeats (TRs), useful algorithms for identifying protein TRs with varied levels of degeneracy are still needed.</p> <p>Results</p> <p>To address limitations of current repeat identification methods, and to provide an efficient and flexible algorithm for the detection and analysis of TRs in protein sequences, we designed and implemented a new computational method called XSTREAM. Running time tests confirm the practicality of XSTREAM for analyses of multi-genome datasets. Each of the key capabilities of XSTREAM (e.g., merging, nesting, long-period detection, and TR architecture modeling) are demonstrated using anecdotal examples, and the utility of XSTREAM for identifying TR proteins was validated using data from a recently published paper.</p> <p>Conclusion</p> <p>We show that XSTREAM is a practical and valuable tool for TR detection in protein and nucleotide sequences at the multi-genome scale, and an effective tool for modeling TR domains with diverse architectures and varied levels of degeneracy. Because of these useful features, XSTREAM has significant potential for the discovery of naturally-evolved modular proteins with applications for engineering novel biostructural and biomimetic materials, and identifying new vaccine and diagnostic targets.</p

Somatic diseases in patients with schizophrenia in general practice: their prevalence and health care

BACKGROUND: Schizophrenia patients frequently develop somatic co-morbidity. Core tasks for GPs are the prevention and diagnosis of somatic diseases and the provision of care for patients with chronic diseases. Schizophrenia patients experience difficulties in recognizing and coping with their physical problems; however GPs have neither specific management policies nor guidelines for the diagnosis and treatment of somatic co-morbidity in schizophrenia patients. This paper systematically reviews the prevalence and treatment of somatic co-morbidity in schizophrenia patients in general practice. METHODS: The MEDLINE, EMBASE, PsycINFO data-bases and the Cochrane Library were searched and original research articles on somatic diseases of schizophrenia patients and their treatment in the primary care setting were selected. RESULTS: The results of this search show that the incidence of a wide range of diseases, such as diabetes mellitus, the metabolic syndrome, coronary heart diseases, and COPD is significantly higher in schizophrenia patients than in the normal population. The health of schizophrenic patients is less than optimal in several areas, partly due to their inadequate help-seeking behaviour. Current GP management of such patients appears not to take this fact into account. However, when schizophrenic patients seek the GP's help, they value the care provided. CONCLUSION: Schizophrenia patients are at risk of undetected somatic co-morbidity. They present physical complaints at a late, more serious stage. GPs should take this into account by adopting proactive behaviour. The development of a set of guidelines with a clear description of the GP's responsibilities would facilitate the desired changes in the management of somatic diseases in these patients

HABIT-an early phase study to explore an oral health intervention delivered by health visitors to parents with young children aged 9-12 months: study protocol.

Background: Parental supervised brushing (PSB) when initiated in infancy can lead to long-term protective home-based oral health habits thereby reducing the risk of dental caries. However, PSB is a complex behaviour with many barriers reported by parents hindering its effective implementation. Within the UK, oral health advice is delivered universally to parents by health visitors and their wider teams when children are aged between 9 and 12 months. Nevertheless, there is no standardised intervention or training upon which health visitors can base this advice, and they often lack the specialised knowledge needed to help parents overcome barriers to performing PSB and limiting sugary foods and drinks.Working with health visitors and parents of children aged 9-24 months, we have co-designed oral health training and resources (Health Visitors delivering Advice in Britain on Infant Toothbrushing (HABIT) intervention) to be used by health visitors and their wider teams when providing parents of children aged 9-12 months with oral health advice.The aim of the study is to explore the acceptability of the HABIT intervention to parents and health visitors, to examine the mechanism of action and develop suitable objective measures of PSB. Methods/design: Six health visitors working in a deprived city in the UK will be provided with training on how to use the HABIT intervention. Health visitors will then each deliver the intervention to five parents of children aged 9-12 months. The research team will collect measures of PSB and dietary behaviours before and at 2 weeks and 3 months after the HABIT intervention. Acceptability of the HABIT intervention to health visitors will be explored through semi-structured diaries completed after each visit and a focus group discussion after delivery to all parents. Acceptability of the HABIT intervention and mechanism of action will be explored briefly during each home visit with parents and in greater details in 20-25 qualitative interviews after the completion of data collection. The utility of three objective measures of PSB will be compared with each other and with parental-self reports. Discussion: This study will provide essential information to inform the design of a definitive cluster randomised controlled trial. Trial registration: There is no database for early phase studies such as ours

Premenstrual enhancement of snake detection in visual search in healthy women

It is well known that adult humans detect images of snakes as targets more quickly than images of flowers as targets whether the images are in color or gray-scale. When such visual searches were performed by a total of 60 adult premenopausal healthy women in the present study to examine whether their performance would fluctuate across the phases of the menstrual cycle, snake detection was found to become temporarily enhanced during the luteal phase as compared to early or late follicular phases. This is the first demonstration of the existence of within-individual variation of the activity of the fear module, as a predictable change in cognitive strength, which appears likely to be due to the hormonal changes that occur in the menstrual cycle of healthy women

Relationships among neurocognition, symptoms and functioning in patients with schizophrenia: a path-analytic approach for associations at baseline and following 24 weeks of antipsychotic drug therapy

<p>Abstract</p> <p>Background</p> <p>Neurocognitive impairment and psychiatric symptoms have been associated with deficits in psychosocial and occupational functioning in patients with schizophrenia. This post-hoc analysis evaluates the relationships among cognition, psychopathology, and psychosocial functioning in patients with schizophrenia at baseline and following sustained treatment with antipsychotic drugs.</p> <p>Methods</p> <p>Data were obtained from a clinical trial assessing the cognitive effects of selected antipsychotic drugs in patients with schizophrenia. Patients were randomly assigned to 24 weeks of treatment with olanzapine (n = 159), risperidone (n = 158), or haloperidol (n = 97). Psychosocial functioning was assessed with the Heinrichs-Carpenter Quality of Life Scale [QLS], cognition with a standard battery of neurocognitive tests; and psychiatric symptoms with the Positive and Negative Syndrome Scale [PANSS]. A path-analytic approach was used to evaluate the effects of changes in cognitive functioning on subdomains of quality of life, and to determine whether such effects were direct or mediated via changes in psychiatric symptoms.</p> <p>Results</p> <p>At baseline, processing speed affected functioning mainly indirectly via negative symptoms. Positive symptoms also affected functioning at baseline although independent of cognition. At 24 weeks, changes in processing speed affected changes in functioning both directly and indirectly via PANSS negative subscale scores. Positive symptoms no longer contributed to the path-analytic models. Although a consistent relationship was observed between processing speed and the 3 functional domains, variation existed as to whether the paths were direct and/or indirect. Working memory and verbal memory did not significantly contribute to any of the path-analytic models studied.</p> <p>Conclusion</p> <p>Processing speed demonstrated direct and indirect effects via negative symptoms on three domains of functioning as measured by the QLS at baseline and following 24 weeks of antipsychotic treatment.</p

Public Versus Private: Does It Matter for Water Conservation? Insights from California

This article asks three connected questions: First, does the public view private and public utilities differently, and if so, does this affect attitudes to conservation? Second, do public and private utilities differ in their approaches to conservation? Finally, do differences in the approaches of the utilities, if any, relate to differences in public attitudes? We survey public attitudes in California toward (hypothetical but plausible) voluntary and mandated water conservation, as well as to price increases, during a recent period of shortage. We do this by interviewing households in three pairs of adjacent public and private utilities. We also survey managers of public and private urban water utilities to see if they differ in their approaches to conservation and to their customers. On the user side we do not find pronounced differences, though a minority of customers in all private companies would be more willing to conserve or pay higher prices under a public operator. No respondent in public utility said the reverse. Negative attitudes toward private operators were most pronounced in the pair marked by a controversial recent privatization and a price hike. Nonetheless, we find that California’s history of recurrent droughts and the visible role of the state in water supply and drought management undermine the distinction between public and private. Private utilities themselves work to underplay the distinction by stressing the collective ownership of the water source and the collective value of conservation. Overall, California’s public utilities appear more proactive and target-oriented in asking their customers to conserve than their private counterparts and the state continues to be important in legitimating and guiding conservation behavior, whether the utility is in public hands or private