Linear-time protein 3-D structure searching with insertions and deletions

<p>Abstract</p> <p>Background</p> <p>Two biomolecular 3-D structures are said to be similar if the RMSD (root mean square deviation) between the two molecules' sequences of 3-D coordinates is less than or equal to some given constant bound. Tools for searching for similar structures in biomolecular 3-D structure databases are becoming increasingly important in the structural biology of the post-genomic era.</p> <p>Results</p> <p>We consider an important, fundamental problem of reporting all substructures in a 3-D structure database of chain molecules (such as proteins) which are similar to a given query 3-D structure, with consideration of indels (<it>i.e.</it>, insertions and deletions). This problem has been believed to be very difficult but its exact computational complexity has not been known. In this paper, we first prove that the problem in unbounded dimensions is NP-hard. We then propose a new algorithm that dramatically improves the average-case time complexity of the problem in 3-D in case the number of indels <it>k </it>is bounded by a constant. Our algorithm solves the above problem for a query of size <it>m </it>and a database of size <it>N </it>in average-case <it>O</it>(<it>N</it>) time, whereas the time complexity of the previously best algorithm was <it>O</it>(<it>Nm</it>^<it>k</it>+1).</p> <p>Conclusions</p> <p>Our results show that although the problem of searching for similar structures in a database based on the RMSD measure with indels is NP-hard in the case of unbounded dimensions, it can be solved in 3-D by a simple average-case linear time algorithm when the number of indels is bounded by a constant.</p

Consumption of alcohol, cigarettes and illegal substances among physicians and medical students in Brandenburg and Saxony (Germany)

<p>Abstract</p> <p>Background</p> <p>Patients regard health care professionals as role models for leading a healthy lifestyle. Health care professionals' own behaviour and attitudes concerning healthy lifestyle have an influence in counselling patients. The aim of this study was to assess consumption of alcohol, cigarettes and illegal substances among physicians and medical students in two German states: Brandenburg and Saxony.</p> <p>Methods</p> <p>Socio-demographic data and individual risk behaviour was collected by an anonymous self-administered questionnaire. Physicians were approached via mail and students were recruited during tutorials or lectures.</p> <p>Results</p> <p>41.6% of physicians and 60.9% of medical students responded to the questionnaire; more than 50% of the respondents in both groups were females. The majority of respondents consumed alcohol at least once per week; median daily alcohol consumption ranged from 3.88 g/d (female medical students) to 12.6 g/d (male physicians). A significantly higher percentage of men (p < 0.05) reported hazardous or harmful drinking compared to women. A quarter of all participating physicians and one third of all students indicated unhealthy alcohol-drinking behaviour. The majority of physicians (85.7%) and medical students (78.5%) were non-smokers. Both groups contained significantly more female non-smokers (p < 0.05). Use of illegal substances was considerably lower in physicians (5.1%) than medical students (33.0%). Male students indicated a significantly (p < 0.001) higher level of illegal drug-use compared to female students.</p> <p>Conclusion</p> <p>More than one third of the medical students and health care professionals showed problematic alcohol-drinking behaviour. Although the proportion of non-smokers in the investigated sample was higher than in the general population, when compared to the general population, medical students between 18-24 reported higher consumption of illegal substances.</p> <p>These results indicate that methods for educating and promoting healthy lifestyle, particularly with respect to excessive alcohol consumption, tobacco use and abuse of illegal drugs should be considered.</p

Why do we treat adolescent idiopathic scoliosis? What we want to obtain and to avoid for our patients. SOSORT 2005 Consensus paper

BACKGROUND: Medicine is a scientific art: once science is not clear, choices are made according to individual and collective beliefs that should be better understood. This is particularly true in a field like adolescent idiopathic scoliosis, where currently does not exist definitive scientific evidence on the efficacy either of conservative or of surgical treatments. AIM OF THE STUDY: To verify the philosophical choices on the final outcome of a group of people believing and engaged in a conservative treatment of idiopathic scoliosis. METHODS: We performed a multifaceted study that included a bibliometric analysis, a questionnaire, and a careful Consensus reaching procedure between experts in the conservative treatment of scoliosis (SOSORT members). RESULTS: The Consensus reaching procedure has shown to be useful: answers changed in a statistically significant way, and 9 new outcome criteria were included. The most important final outcomes were considered Aesthetics (100%), Quality of life and Disability (more than 90%), while more than 80% of preferences went to Back Pain, Psychological well-being, Progression in adulthood, Breathing function, Scoliosis Cobb degrees (radiographic lateral flexion), Needs of further treatments in adulthood. DISCUSSION: In the literature prevail outcome criteria driven by the contingent treatment needs or the possibility to have measurement systems (even if it seems that usual clinical and radiographic methods are given much more importance than more complex Disability or Quality of Life instruments). SOSORT members give importance to a wide range of outcome criteria, in which clinical and radiographic issues have the lowest importance. CONCLUSION: We treat our patients for what they need for their future (Breathing function, Needs of further treatments in adulthood, Progression in adulthood), and their present too (Aesthetics, Disability, Quality of life). Technical matters, such as rib hump or radiographic lateral alignment and rotation, but not lateral flexion, are secondary outcomes and only instrumental to previously reported primary outcomes. We advocate a multidimensional, comprehensive evaluation of scoliosis patients, to gather all necessary data for a complete therapeutic approach, that goes beyond x-rays to reach the person and the family

Investigations regarding the mutagenicity of o-chloroaniline and m- cloroaniline in tests with mammalians in vitro and Drosophila melanogaster

Dit onderzoek is uitgevoerd om aanvullende gegevens te verkrijgen t.b.v. de classificatie van de genoemde stoffen in het kader van de Beoordelingscriteria Waterverontreiniging. Hoewel de resultaten een zwakke mutagene werking niet geheel kunnen uitsluiten, wordt gecon- cludeerd dat voor het huidige kader de stoffen niet als mutageen dienen te worden beschouwd.DGMH/BWS-

Clastogenic and mutagenic activity of methylene chloride in tests with V79 Chinese hamster cells and L5178Y mouse lymphoma cells in vitro, and with Drosophila melanogaster

Ten behoeve van de toxicologische evaluatie van methyleenchloride in het kader van het opstellen van het Basisdocument Methyleenchloride werd methyleenchloride onderzocht in verschillende eukaryotische mutageniteitstesten. Methyleenchloride, onderzocht in afwezigheid van metabolische activering, induceerde chromosoomafwijkingen maar geen genmutaties in zoogdiercellen in vitro. Een recessief-letaaltest met Drosophila melanogaster, na inhalatoire blootstelling, was negatief.RIV

Investigation of the mutagenic action of methacrylonitril on microorganisms, Drosophila melanogaster and L5178Y mouse lymphoma cells

Met methacrylonitril is bij concentraties t/m 5 mmol/l (336 mg/l) lucht, behoudens een geringe verhoging bij 2 mmol/l, en 100 mmol/l (6,71 g/l) bouillon geen mutagene werking gevonden met Klebsiella pneumoniae. Met de Salmonella typhimurium stammen TA 98, TA 100, TA 1530 TA 1535 en TA 1950 is bij concentraties tot 1 mmol/l (67,1 mg/l) lucht en 1,19 mmol (0,8 g) per selectieplaat geen mutagene werking gevonden. Met Drosophila melanogaster is bij injectie van 0,2 mu-l van 300 mmol/l methacrylonitril geen mutagene werking gevonden. Met L5178Y muize-lymfoomcellen is geen mutagene werking van methacrylonitril gevonden bij geteste concentraties van 29,8 tot 74,4 mmol/l (2,0-4,99 g/l), zonder metabolische activering en bij 9,5 tot 23,8 mmol/l (0,64- 1,60 g/l), in aanwezigheid van metabolische activering. Methacrylonitril is als een niet mutagene stof geclassificeerd.HI

Investigation of the mutagenic activity of acrylonitril on microorganisms, Drosophila melanogaster and L5178Y mouse-lymphatic cells

Acrylonitril was mutageen bij 5 mmol/l in de fluctuatietest zonder metabolische activering ; in gasfase werd bij 0,5 mmol/l lucht een mutagene werking gevonden. Deze stof was ook mutageen in de Ames-test voor Salmonella typhimurium TA1535 (15 mmol/plaat) met metabolische activering doch niet met de stammen TA98 en TA100. In de gasfase werd in de Ames-test geen mutagene werking gevonden, groeiremming trad op bij ca. 0,1 mmol/l lucht. Met acrylonitril werd geen mutagene werking gevonden op Drosophila melanogaster (0,2 ul van een 10 of 15 mmol/l oplossing). Met L5178Y muize lymfoomcellen werd zonder metabolische activering een mutagene werking gevonden vanaf 11 mmol/l. Met metabolische activering werd of bij 4 uur (doch niet na 2 uur) of bij 10% S9 (doch niet bij 5% S9) een mutageen effect van acrylonitril gevonden. Ook in aanwezigheid van embryocellen van Syrische hamsters werd een mutageen effect of L5178Y cellen (0,5 en 1,5 mmol/l gedurende 18 uur) gevonden op het TK-gen en het HPRT-gen.HI

Investigation of the mutagenic activity of divinylbenzene with microorganisms, Drosophila melanogaster and L5178Y mouse lymphoma cells

Met divinylbenzeen is bij hoeveelheden van 55 mul/l (0,385mmol/l of 50 mg/l) of minder met Klebsiella pneumoniae en bij hoeveelheden van 0,5 mul of minder per selectieplaat met de Salmonella typhimurium stammen TA 98 en TA 100, met en zonder metabolische activering, geen mutagene werking gevonden. Ook bij toediening van divinylbenzeen (injectie van 0,2 mul van een 100 mmol/l oplossing) aan Drosophila melanogaster is geen mutagene werking vastgesteld. Met muizelymfoom cellen L5178Y, met en zonder metabolische activering, is bij hoeveelheden van 0,035 mul/ml of minder geen mutagene activiteit van divinylbenzeen gevonden. Bij hogere concentraties dan bovengenoemde had divinylbenzeen groeiremmende en/of cytotoxische effecten. Divinylbenzeen is een stof waarmede in testen voor genmutaties geen mutagene werking is gevonden.HI

Onderzoek naar de mutagene werking van 2,3-epoxypropylacrylaat met microorganismen, Drosophila melanogaster en L5178Y muize-lymfoomcellen

2,3-Epoxypropylacrylaat of glycidyacrylaat bleek mutageen te zijn voor Klebsiella pneumoniae (0,5 mmol/l en hoger), Salmonella typhimurium TA 1535 (vanaf 0,004 mg of + 0,02 mumol per plaat), Salmonella typhimurium TA 100 (vanaf 0,04 mg of + 0,2 mumol per plaat), de bananevlieg Drosophila melanogaster (bij injectie van 0,2 mul van een 10 mmol of 25 mmol oplossing) en L5178Y muizelymfoomcellen (vanaf 10-3 ml/l of 0,0087 mmol/l). Met Salmonella typhimurium TA 98 werd bij de hoogste dosering (0,4 mg per plaat) geen mutagene werking gevonden. Met Salmonella typhimurium TA 1538 werd alleen bij de hoogste dosering (0,4 mg per plaat) een zwak mutagene werking gevonden. 2,3-Epoxypropylacrylaat is mutageen en induceert basenpaar substituties en cytotoxische effecten bij Drosophila melanogaster met 25 mmol oplossing en muize- lymfoomcellen van 0,001 ml/l