Adaptive metabolic changes in CADASIL white matter

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an important genetic cause of stroke, but pathogenic mechanisms and functional alterations remain poorly characterized. The purpose of this study was to investigate adaptive metabolic and functional changes in white matter hyperintensities and normal-appearing white matter in CADASIL patients using 1H-magnetic resonance spectroscopic imaging (MRSI). Eight CADASIL patients and eight matched healthy controls were studied. 1H-MRSI data were acquired on a 3T scanner using high-resolution multi-spin echo spectroscopic imaging (T E=288ms) and non-accelerated medium-resolution MRSI (T E=35ms). MRI of all CADASIL patients demonstrated characteristic white matter hyper-intensities (WMH) in the subcortical periventricular white matter. Cre/Cho, Glx/Cho and Glx/Cre ratios were significantly decreased in WMH compared to normal-appearing white matter (NAWM) in patients, while Glx/Cre and mI/Cho ratios in NAWM showed a significant increase compared to healthy controls. In severely affected patients derived spectra reflected a decrease of NAA concentrations inside WMH when compared to healthy white matter. Metabolic abnormalities in WMH of CADASIL patients are compatible with axonal loss due to chronic micro-infarctions. Increased Glx/Cre and mI/Cho ratios in NAWM indicate an augmented glial cell density and decreased neuronal cell density. This altered tissue composition might be interpreted as adaptation to hypoperfusion and impaired vasoreactivity in NAWM of CADASIL patients. Our data might contribute to the general understanding of adaptive processes induced by hypoperfusion and chronic ischemi

Renal AA-amyloidosis in intravenous drug users - a role for HIV-infection?

Background: Chronic renal disease is a serious complication of long-term intravenous drug use (IVDU). Recent reports have postulated a changing pattern of underlying nephropathy over the last decades. Methods: Retrospective investigation including all patients with prior or present IVDU that underwent renal biopsy because of chronic kidney disease between 01.04.2002 and 31.03.2012 in the city of Frankfurt/Main, Germany. Results: Twenty four patients with IVDU underwent renal biopsy because of progressive chronic kidney disease or proteinuria. Renal AA-amyloidosis was the predominant cause of renal failure in 50% of patients. Membranoproliferative glomerulonephritis (GN) was the second most common cause found in 21%. Patients with AA-amyloidosis were more likely to be HIV infected (67 vs.17%; p=0.036) and tended to have a higher rate of repeated systemic infections (92 vs. 50%; p=0.069). Patients with AA-amyloidosis presented with progressive renal disease and nephrotic-range proteinuria but most patients had no peripheral edema or systemic hypertension. Development of proteinuria preceded the decline of GFR for approximately 1--2 years. Conclusions: AA-amyloidosis was the predominant cause of progressive renal disease in the last 10 years in patients with IVDU. The highest rate of AA-amyloidosis observed was seen in HIV infected patients with IVDU. We speculate that chronic HIV-infection as well as the associated immunosuppression might promote development of AA-amyloidosis by increasing frequency and duration of infections acquired by IVDU

Ribonucleoparticle-independent transport of proteins into mammalian microsomes

There are at least two different mechanisms for the transport of secretory proteins into the mammalian endoplasmic reticulum. Both mechanisms depend on the presence of a signal peptide on the respective precursor protein and involve a signal peptide receptor on the cis-side and signal peptidase on the trans-side of the membrane. Furthermore, both mechanisms involve a membrane component with a cytoplasmically exposed sulfhydryl. The decisive feature of the precursor protein with respect to which of the two mechanisms is used is the chain length of the polypeptide. The critical size seems to be around 70 amino acid residues (including the signal peptide). The one mechanism is used by precursor proteins larger than about 70 amino acid residues and involves two cytosolic ribonucleoparticles and their receptors on the microsomal surface. The other one is used by small precursor proteins and relies on the mature part within the precursor molecule and a cytosolic ATPase

Информационная система технического сервиса машинотракторного парка

Предоставление услуг технического сервиса требует предоставления гарантий качества этих услуг. Результаты исследований ведущих специалистов в этой области не всегда доступны инженерам сельскохозяйственных предприятий, поэтому существует необходимость в разработке методик оценки качества клиентом или подтверждения обеспечения качества поставщиком услуг технического сервиса. Проект системы технического сервиса машинотракторного парка, включающей в себя совокупность взаимосвязанных и взаимообусловленных ее элементов - процессов, происходящих в машинах; технологий технического сервиса; исполнителей технического сервиса - определяемую и направляемую целью технического сервиса - поддержание работоспособности сельскохозяйственной техники, позволяет сформировать методику оценки качества. Показатель качества представляет собой произведение частных коэффициентов, учитывающих степень соответствия выполненных объемов работ требуемым объемам; степень соответствия периодичности ТО требуемым значениям; степень соответствия технологий ТО и ремонта процессам в подсистемах; достаточность компетенций исполнителей для реализации технологий ТО и ремонта; достаточность перечня работ, потенциально выполняемых исполнителями технического сервиса, для обслуживания определенного вида машинотракторных агрегатов. Степень соответствия периодичности может обеспечиваться соблюдением требований нормативно-технической документации. Объемы работ технического сервиса могут быть обеспечены работой группы исполнителей технического сервиса. Предлагается вариант методики оценки компетенций исполнителей технического сервиса. Вместе с тем разработанная информационная система технического сервиса позволяет выявить взаимосвязи, определяющие качество технического сервиса.Providing technical services also requires providing quality assurance of these services. Results of leading experts' research in this field is not always available for engineers of agricultural companies, that is why there is need for development of a customer quality assessment method or a method of quality assurance by technical services suppliers. Project of machines and tractor fleet technical service system which included an assembly of interrelated and interdependent elements - processes running in machines, technologies of technical service, performers of technical service - is defined and directed by the aim of technical service which consists in maintaining operability of agricultural equipment, allows to create a method of quality assessment. The quality index represents multiplication of partial factors which take into consideration degree of correspondence of performed volume of works to the required volume, degree of correspondence of maintenance intervals to the required intervals, degree of conformity of repair and maintenance technologies to processes in subsystems; sufficiency of performers competence for implementation of repair and maintenance; sufficiency of range of works potentially carried out by technical service performers for maintenance of a certain types of machine- and tractor aggregates. The degree of correspondence of intervals can be ensured by meeting the requirements of standards and technical documentation. The volume of technical services works can be provided by involving a group of technical service performers. A variant of technical service performers' competence assessment method is suggested. Along with that an information system of technical service is developed which allows to state interdependencies determining quality of technical service

Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study.

PurposeThe KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2-positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% v 55.7%; P = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE.MethodsPatients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery).ResultsOf patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95% CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7%] v 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95% CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95% CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8% v 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% v 9.9%) and AEs leading to treatment discontinuation (18.4% v 3.8%) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment.ConclusionCompared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment

Potential drivers of human tick-borne encephalitis in the orebro region of Sweden, 2010-2021

Incidence of tick-borne encephalitis (TBE) has increased during the last years in Scandinavia, but the underlying mechanism is not understood. TBE human case data reported between 2010 and 2021 were aggregated into postal codes within orebro County, south-central Sweden, along with tick abundance and environmental data to analyse spatial patterns and identify drivers of TBE. We identified a substantial and continuing increase of TBE incidence in orebro County during the study period. Spatial cluster analyses showed significant hotspots (higher number of cases than expected) in the southern and northern parts of orebro County, whereas a cold spot (lower number of cases than expected) was found in the central part comprising orebro municipality. Generalised linear models showed that the risk of acquiring TBE increased by 12.5% and 72.3% for every percent increase in relative humidity and proportion of wetland forest, respectively, whereas the risk decreased by 52.8% for every degree Celsius increase in annual temperature range. However, models had relatively low goodness of fit (R-2 < 0.27). Results suggest that TBE in orebro County is spatially clustered, however variables used in this study, i.e., climatic variables, forest cover, water, tick abundance, sheep as indicator species, alone do not explain this pattern

The Interplay of People and Technologies

Histories of innovation are prototypical success stories. The advent of the wheel, of writing, printing, the steam engine or computers: where would we be without these path-breaking technological innovations and their global consequences? At least retrospectively, innovations appear as linear, straightforward processes. However, this view is too simplistic. Innovations are not self-evident new elements of life but meet social and technological resistance. In accounts of past innovations, we also often forget that their price is always an irremediable loss of knowledge and practical skills. This collection of essays shows that innovations, both ancient and more recent ones, are located in a network of pre-existing life-worlds. The authors elucidate the wide and often unrecognized impacts of innovations on social structures and cultural practices. Case studies from ancient Mesopotamia, Egypt, central Europe and the modern world highlight the preconditions and off-ignored secondary effects of innovation. They address the complex social negotiations and the multitude of unforeseen and unplanned changes which accompany the New, rather than focusing on intended changes, which are usually understood as improvements and ways to broaden possibilities for action. Our ultimate goal is to investigate the complex entangle ments of innovations in past and present worlds and deepen our understanding of mechanisms of cultural change

SchussenAktivplus: reduction of micropollutants and of potentially pathogenic bacteria for further water quality improvement of the river Schussen, a tributary of Lake Constance, Germany

The project focuses on the efficiency of combined technologies to reduce the release of micropollutants and bacteria into surface waters via sewage treatment plants of different size and via stormwater overflow basins of different types. As a model river in a highly populated catchment area, the river Schussen and, as a control, the river Argen, two tributaries of Lake Constance, Southern Germany, are under investigation in this project. The efficiency of the different cleaning technologies is monitored by a wide range of exposure and effect analyses including chemical and microbiological techniques as well as effect studies ranging from molecules to communities

Капитальный ремонт магистрального нефтепровода в условиях болотистой местности

Объектом исследования является ремонтируемый участок магистрального трубопровода "Александровское – Анжеро-Судженск", находящийся на 282 км трассы и проходящий через болота II типа. Цель работы – Проведение капитального ремонта магистрального нефтепровода методом вырезки/врезки катушки в условиях болот. В процессе исследования проводились расчеты эксплуатационных затрат на ремонт врезкой катушки и ремонт композитной муфтой, а также расчеты трубопровода на прочность, деформативность, общую устойчивость в продольном направлении к различным нагрузкам и воздействиям, в данном случае эксплуатация трубопровода в условиях болотистой местности и устойчивость против всплытия.The object of the research is the repaired section of the Aleksandrovskoye - Anzhero-Sudzhensk trunk pipeline, which is located on the 282 km of the route and passes through type II swamps. The purpose of the work is to carry out the overhaul of the main oil pipeline by cutting / tapping the coil in wetland conditions. In the course of the study, calculations were made of the operating costs for repairing the coil insert and repair with a composite coupling, as well as calculations of the pipeline for strength, deformability, and overall resistance in the longitudinal direction to various loads and impacts, in this case, the operation of the pipeline in wetland conditions and resistance to ascent