"May You Have a Strong (-Typed) Foundation", Why Strong-Typed Programming Languages Do Matter

Programming efficient and reliable code can be considered a non-trivial task, as it requires deep understanding of the problem to be solved along with good programming skills. However, software frameworks and programming paradigms can provide a dependable infrastructure upon which better programs can be written and deployed. This allows engineers to focus mainly on their task, while relying on the underlying run-time environment for taking care of low-level programming issues, such as memory allocation and disposal, typing consistency and interface compliance. In this paper, we argue that strong-typed programming languages and paradigms offer a valid support for the production of reliable programs. Aware of the challenges of formal measurement metrics for code quality, we present the benefits of strong-typing by considering a practical application: The design and implementation of RoboX, a tour-guide robot for the Swiss National Exhibition Expo.02. The example is extremely well suited for such a discussion, since complex mechatronic applications can be considered critical systemsi.e. systems whose failure may endanger missions, lives and societythus their reliability has to be made a prime concern

РАК ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ И НАСЛЕДСТВЕННЫЕ СИНДРОМЫ

The aim of this study is to assess relative risk of prostate cancer (PC) and other tumors in families of patients with multiple primary malignancies (MPM) and the syndrome of hereditary nonpolyposis colorectal cancer (HNPCC). The study is based on data from the cancer register of families that includes information on 560 patients with MPM, 126 families with HNPCC and their first-degree relatives. Incidence of these diseases in population served as the control.Among 560 probands with PPN 217 (38.7%) were male and 343 (61.3%) – female. Only 12 (2.1%) male patients had tumor in the prostate. In these patients 24 tumors were identified. Two patients had synchronous tumors, other ten patients had metachronous. Eight patients with prostate cancer had tumors of other organs: 5 – in rectum, 2 – in colon and 1 – in bladder. As a second tumor prostate cancer was diagnosed in 4 patients, three of them had rectal cancer and one – colon cancer. Only 2 (0.3%) patients had prostate cancer as a primary tumor. Clinical and genealogical information achieved from 543 patients with MPM, including in 206 male probands. Among 3637 first-degree relatives of probands with MPM prostate cancer was diagnosed in 2  (0.11±2.3%) patients that was 1.7 times higher than in population (0.063±0.0019%). The relative risk of prostate cancer for relatives of patients from families with HNPCC syndrome was 0.8 ± 6.3% that was 12/7 times higher than  in the control group (p <0.05). The estimation of the relative risk in families of male probands was perfprmed. Among 1460 male relatives with MPM only 1 (0.14%) case of prostate cancer was diagnosed (son of proband). Among 42 families of male probands with HNPCC syndrome, prostate cancer was detected in 2 (1.3%) brothers that exceeds population risk 20.6 times. Although the molecular mechanisms and pathogenesis of prostate cancer in such families is unknown, its association with a HNPCC-syndrome and possibly MPM-syndrome is obvious.Higher relative risk of developing prostate cancer for male relatives of probands with MPM and HNPCC syndrome presupposes inherited genetically determined predisposition to disease development. Further molecular and genetic studies are needed to determine the genetic basis of predisposition to prostate cancer in these families.Цель исследования — оценить относительный риск рака предстательной  железы (РПЖ) и других (внепростатных)  опухолей в семьях больных с первично-множественными  злокачественными  новообразованиями   (ПМЗН) и с синдромом  наследственного неполипозного колоректального рака (HNPCC). Материалом для исследования  послужили данные регистра раковых семей,  включающий сведения  о 560 больных с ПМЗН, 126 семей с HNPCC и их родственников первой степени родства.  В качестве контроля служили популяционные частоты указанных заболеваний.Среди 560 пробандов с ПМЗН было 217 (38.7%) мужчин и 343 (61.3%)  женщин. Только у 12 (2.1%) пациентов-мужчин одна из опухолей поражала  ПЖ. У них выявлены 24 опухоли. У двух  из них опухоли были синхронными, а у 10 — метахронными. У 8 пациентов с РПЖ вторые опухоли локализовались:  в прямой кишке (5), ободочной кишке (2) и мочевом  пузыре (1). В качестве  второй опухоли РПЖ наблюдали  у 4 пациентов:  у 3 с раком прямой кишки и у 1 — раком ободочной  кишки. Только у 2 (0.3%) пациентов первой опухолью был РПЖ. Клинико-генеалогические  сведения  удалось  получить у 543 пациентов  с ПМЗН, в том числе у 206 пробандов-мужчин.  Среди 3637 родственников первой степени родства пробандов с ПМЗН РПЖ выявлен  у 2 (0.11±2.3%), что в 1.7 раза превышает популяционный риск (0.063±0.0019%). Относительный  риск РПЖ для родственников  пациентов  из семей с синдромом  HNPCC составляет 0.8±6.3% и превышает таковой в контрольной  группе в 12.7 раз (р<0.05).  Проведена оценка относительного риска в семьях пробандов-мужчин. Среди 1460 родственников-мужчин с ПМЗН выявлен 1 (0.14%) случай РПЖ — у сына. В 42 семьях пробандов-мужчин  с синдромом  HNPCC РПЖ был выявлен у 2 (1.3%) братьев,  что превышает популяционный риск в 20.6 раза. Хотя молекулярный  механизм  и патогенез  РПЖ в описанных семьях остается неизвестным, его ассоциация с синдромом  HNPCC и, возможно, с синдромом полинеоплазий, очевидна. Высокий относительный риск заболеть  РПЖ для кровных родственников-мужчин пробандов с ПМЗН и синдромом  HNPCC предполагает наличие унаследованной генетически обусловленной предрасположенности  к развитию болезни.  Необходимы молекулярно-генетические исследования,  чтобы определить  генетическую основу подверженности к раку предстательной  железы в этих семьях. Не исключено, что это может быть связано с общими этиологическими факторами

Molecular surveillance of Plasmodium vivax dhfr and dhps mutations in isolates from Afghanistan

<p>Abstract</p> <p>Background</p> <p>Analysis of dihydrofolate reductase (<it>dhfr</it>) and dihydropteroate synthase (<it>dhps</it>) mutations in <it>Plasmodium vivax </it>wild isolates has been considered to be a valuable molecular approach for mapping resistance to sulphadoxine-pyrimethamine (SP). The present study investigates the frequency of SNPs-haplotypes in the <it>dhfr </it>and <it>dhps </it>genes in <it>P. vivax </it>clinical isolates circulating in two malaria endemic areas in Afghanistan.</p> <p>Methods</p> <p><it>P. vivax </it>clinical isolates (n = 171) were collected in two different malaria endemic regions in north-west (Herat) and east (Nangarhar) Afghanistan in 2008. All collected isolates were analysed for SNP-haplotypes at positions 13, 33, 57, 58, 61, 117 and 173 of the <it>pvdhfr </it>and 383 and 553 of the <it>pvdhps </it>genes using PCR-RFLP methods.</p> <p>Results</p> <p>All 171 examined isolates were found to carry wild-type amino acids at positions 13, 33, 57, 61 and 173, while 58R and 117N mutations were detected among 4.1% and 12.3% of Afghan isolates, respectively. Based on the size polymorphism of <it>pvdhfr </it>genes at repeat region, type B was the most prevalent variant among Herat (86%) and Nangarhar (88.4%) isolates. Mixed genotype infections (type A/B and A/B/C) were detected in only 2.3% (2/86) of Herat and 1.2% (1/86) of Nangarhar isolates, respectively. The combination of <it>pvdhfr </it>and <it>pvdhps </it>haplotypes among all 171 samples demonstrated six distinct haplotypes. The two most prevalent haplotypes among all examined samples were wild-type (86%) and single mutant haplotype I₁₃P₃₃F₅₇S₅₈T₆₁<b>N </b>₁₁₇I_173/A₃₈₃A₅₅₃(6.4%).</p> <p>Double (I₁₃P₃₃S₅₇<b>R</b>₅₈T₆₁<b>N</b>₁₁₇I₁₇₃/A₃₈₃A₅₅₃) and triple mutant haplotypes (I₁₃P₃₃S₅₇<b>R </b>₅₈T₆₁<b>N</b>₁₁₇I₁₇₃/<b>G</b>₃₈₃A₅₅₃) were found in 1.7% and 1.2% of Afghan isolates, respectively. This triple mutant haplotype was only detected in isolates from Herat, but in none of the Nangarhar isolates.</p> <p>Conclusion</p> <p>The present study shows a limited polymorphism in <it>pvdhfr </it>from Afghan isolates and provides important basic information to establish an epidemiological map of drug-resistant vivax malaria, and updating guidelines for anti-malarial policy in Afghanistan. The continuous usage of SP as first-line anti-malarial drug in Afghanistan might increase the risk of mutations in the <it>dhfr </it>and <it>dhps </it>genes in both <it>P. vivax </it>and <it>Plasmodium falciparum </it>isolates, which may lead to a complete SP resistance in the near future in this region. Therefore, continuous surveillance of <it>P. vivax </it>and <it>P. falciparum </it>molecular markers are needed to monitor the development of resistance to SP in the region.</p

FMR1 premutation and full mutation molecular mechanisms related to autism

Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5′ un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are important for synaptic development and plasticity. Furthermore, many of these genes, when mutated, have been linked to autism in the general population, which may explain the high comorbidity that exists between FXS and autism spectrum disorders (ASD). Additionally, premutation repeat expansions (55 to 200 CGG repeats) may also give rise to ASD through a different molecular mechanism that involves a direct toxic effect of FMR1 mRNA. It is believed that RNA toxicity underlies much of the premutation-related involvement, including developmental concerns like autism, as well as neurodegenerative issues with aging such as the fragile X-associated tremor ataxia syndrome (FXTAS). RNA toxicity can also lead to mitochondrial dysfunction, which is common in older premutation carriers both with and without FXTAS. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in idiopathic autism. Research regarding dysregulation of neurotransmitter systems caused by the lack of FMRP in FXS, including metabotropic glutamate receptor 1/5 (mGluR1/5) pathway and GABA pathways, has led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism