Stand-alone hydropower plants based on magnetoelectric generator and transistor converters

В докладе рассматриваются вопросы разработки мини-ГЭС на базе синхронного генератора с постоянными магнитами и с активным выпрямителем и инвертором напряжения в качестве преобразователей энергии. Обсуждаются вопрос выбора силовых частей, структура системы управления и синтез регуляторов активного выпрямителя напряжения. Приведены результаты применения наблюдателя тока нагрузки АВН.The report discusses the development of mini-hydro -based synchronous permanent magnet generator and active rectifier and inverter voltage as energy converters . Discussed the question of choice of power units, control system structure and synthesis of active rectifier voltage regulators . The results of application of the load current observer VAR

Research the methods of construction positional ac drive

В докладе рассматриваются вопросы построения позиционных электроприводов переменного тока. Обсуждаются различные варианты построения структуры системы управления и синтеза регуляторов. Приведены результаты теоретических исследований системы позиционирования с частотно-регулируемым асинхронным электроприводом.The report below concentrates on the construction of positional AC drives. There discussed the various methods of construction the structure of control system and the synthesis of controllers. There presented the results of theoretical researches positional system with frequency-controlled induction motor drive

АТРЕЗИЯ ТОЛСТОЙ КИШКИ В СОЧЕТАНИИ С БОЛЕЗНЬЮ ГИРШПРУНГА: РЕДКОЕ КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

Introduction. Hirschsprung’s disease is a congenital anomaly characterized by the absence of ganglion cells in submucosal and intramuscular layers of intestinal wall that leads to the intestinal obstruction. 70–80 % of cases are isolated malformation but it can be combined with chromosomal abnormalities and other malformations. Coexistence of Hirschsprung’s disease with intestinal atresia is extremely rare. It can cause significant difficulties in diagnostics and treatment.Material and methods. Patient A, a boy, was transferred to the surgical department at the age of two days with a history of intestinal obstruction. He had abdominal X-ray studies: intestinal obstruction. The contrast enema showed microcolon that was coiled in the pelvis. Patient was prepared to the surgical treatment. Intraoperatively colonic atresia was identified at 10 sm from the ileocecal valve. A double colostomy was performed to the child and biopsy on the level of mucous fistula was taken. Histological study showed the aganglionosis of the distal colon. At the age of 4 months, the patient underwent Soave-Swenson endorectal pullthrough procedure with intraoperative extended express-biopsy that confirmed the absence of ganglion cells in whole distal bowel. The aganglionic part was resected, the ileocecal valve with the part of the colon of 10 cm long was mobilized and the endorectal bringing the colon down to the perineum was performed by Soave – Swenson. Postoperative recovery was uneventful.Results. A high index of suspicion is required to promptly diagnose Hirschsprung’s disease in a child with colonic atresia despite the rare combination of these two anomalies. In this case the histological study allowed to recognize association of colonic atresia with Hirschsprung’s disease and helped to avoid complications after further surgery.Conclusions. Early detection of coexisting of these two anomalies helps to prevent the development of serious postoperative complications. Введение. Болезнь Гиршпрунга – врожденное заболевание, которое характеризуется отсутствием нервных ганглиев в подслизистом и межмышечном слоях кишечной стенки, приводящее к нарушению пассажа содержимого по желудочно-кишечному тракту. В 70–80 % случаев является изолированным пороком развития, однако может сочетаться с хромосомными патологиями и другими аномалиями. Сочетание болезни Гиршпрунга с атрезией тонкой или толстой кишки встречается довольно редко и может вызвать значительные трудности в диагностике и лечении.Материал и методы. Мальчик А. был переведен в стационар в возрасте 2 суток жизни с клиникой низкой кишечной непроходимости. Обследован рентгенологически: картина кишечной непроходимости. При ирригографии, помимо картины микроколона, обращало на себя внимание необычное расположение толстой кишки в малом тазу. Подготовлен к оперативному лечению. Интраоперационно выявлена атрезия толстой кишки на расстоянии 10 см от илеоцекального угла. Ребенку наложена двойная колостома, взята биопсия отводящей и приводящей кишки. По гистологическому заключению – аганглиоз отключенной кишки. В 4 месяца выполнена радикальная операция. Интраоперационно произведена расширенная экспресс-биопсия толстой кишки, ганглии выявлены только в приводящем отделе. Аганглионарный участок резецирован, мобилизован илеоцекальный угол с участком толстой кишки длиной 10 см и произведено эндоректальное низведение толстой кишки на промежность по Soave – Swenson. Послеоперационный период – без хирургических осложнений.Результаты. Несмотря на довольно редкое сочетание этих двух патологий, при оперативном лечении по поводу атрезии толстой кишки необходимо помнить о вероятности аганглиоза отводящего отдела. В данном случае гистологическое исследование участка отводящей кишки позволило рано выявить сочетание порока с болезнью Гиршпрунга и избежать возможных осложнений при последующем оперативном вмешательстве. Выводы. Раннее выявление сочетания двух аномалий позволит предупредить развитие тяжелых послеоперационных осложнений.

Integration Preferences of Wildtype AAV-2 for Consensus Rep-Binding Sites at Numerous Loci in the Human Genome

Adeno-associated virus type 2 (AAV) is known to establish latency by preferential integration in human chromosome 19q13.42. The AAV non-structural protein Rep appears to target a site called AAVS1 by simultaneously binding to Rep-binding sites (RBS) present on the AAV genome and within AAVS1. In the absence of Rep, as is the case with AAV vectors, chromosomal integration is rare and random. For a genome-wide survey of wildtype AAV integration a linker-selection-mediated (LSM)-PCR strategy was designed to retrieve AAV-chromosomal junctions. DNA sequence determination revealed wildtype AAV integration sites scattered over the entire human genome. The bioinformatic analysis of these integration sites compared to those of rep-deficient AAV vectors revealed a highly significant overrepresentation of integration events near to consensus RBS. Integration hotspots included AAVS1 with 10% of total events. Novel hotspots near consensus RBS were identified on chromosome 5p13.3 denoted AAVS2 and on chromsome 3p24.3 denoted AAVS3. AAVS2 displayed seven independent junctions clustered within only 14 bp of a consensus RBS which proved to bind Rep in vitro similar to the RBS in AAVS3. Expression of Rep in the presence of rep-deficient AAV vectors shifted targeting preferences from random integration back to the neighbourhood of consensus RBS at hotspots and numerous additional sites in the human genome. In summary, targeted AAV integration is not as specific for AAVS1 as previously assumed. Rather, Rep targets AAV to integrate into open chromatin regions in the reach of various, consensus RBS homologues in the human genome

Human Galectin 3 Binding Protein Interacts with Recombinant Adeno-Associated Virus Type 6

Recombinant adeno-associated viruses (rAAVs) hold enormous potential for human gene therapy. Despite the well-established safety and efficacy of rAAVs for in vivo gene transfer, there is still little information concerning the fate of vectors in blood following systemic delivery. We screened for serum proteins interacting with different AAV serotypes in humans, macaques, dogs, and mice. We report that serotypes rAAV-1, -5, and -6 but not serotypes rAAV-2, -7, -8, -9, and -10 interact in human sera with galectin 3 binding protein (hu-G3BP), a soluble scavenger receptor. Among the three serotypes, rAAV-6 has the most important capacities for binding to G3BP. rAAV-6 also bound G3BP in dog sera but not in macaque and mouse sera. In mice, rAAV-6 interacted with another protein of the innate immune system, C-reactive protein (CRP). Furthermore, interaction of hu-G3BP with rAAV-6 led to the formation of aggregates and hampered transduction when the two were codelivered into the mouse. Based on these data, we propose that species-specific interactions of AAVs with blood proteins may differentially impact vector distribution and efficacy in different animal models

Promised Land? Immigration, Religiosity, and Space in Southern California

This article looks at how immigrants and their supporters appropriate and use religious space and other public spaces for religious and socio-political purposes in Southern California. While the everyday living conditions of many immigrants, particularly the unauthorized Latino immigrants, force unto them an embodied disciplinarity that maintains spatialities of restricted citizenship, the public appropriations of space for and through religious practices allow for them -even if only momentarily -to express an embodied transgression. This practice in public space helps realize spaces of freedom and hope, however ephemerally. Potentially, these rehearsing exercises can help revert internalized disempowering subjectivities and create social empowerment. Negative stereotypes about immigrants held by the larger public can also be challenged through these spatial practices, as the public demonstrations make visible the invisible. We focus on “Posadas Without Borders” and “the New Sanctuary Movement,” considering both the role of progressive civic and religious institutions in supporting immigrants and the agency of the immigrants themselves. The theoretical analysis builds on concepts drawn from a conversation between geography and religious and theological studies. We use a triangulated methodological approach that includes observation and participant observation, content-analysis of multimedia, interviews, and intellectual advocacy for the immigrant movement. The cases discussed here show that progressive religious groups and coalitions can be important allies to progressive planners, geographers, and policy makers in advancing social and environmental justice for the disenfranchised. They also show that the theological underpinnings of such groups share a lot in common with planning epistemologies for the just city

Substitution of adeno-associated virus Rep protein binding and nicking sites with human Chromosome 19 sequences

<p>Abstract</p> <p>Background</p> <p>Adeno-associated virus type 2 (AAV2) preferentially integrates its DNA at a ~2 kb region of human chromosome 19, designated <it>AAVS1 </it>(also known as <it>MBS85</it>). Integration at <it>AAVS1 </it>requires the AAV2 replication (Rep) proteins and a DNA sequence within <it>AAVS1 </it>containing a 16 bp Rep recognition sequence (RRS) and closely spaced Rep nicking site (also referred to as a terminal resolution site, or <it>trs</it>). The AAV2 genome is flanked by inverted terminal repeats (ITRs). Each ITR contains an RRS and closely spaced <it>trs</it>, but the sequences differ from those in <it>AAVS1</it>. These ITR sequences are required for replication and packaging.</p> <p>Results</p> <p>In this study we demonstrate that the <it>AAVS1 </it>RRS and <it>trs </it>can function in AAV2 replication, packaging and integration by replacing a 61 bp region of the AAV2 ITR with a 49 bp segment of <it>AAVS1 </it>DNA. Modifying one or both ITRs did not have a large effect on the overall virus titers. These modifications did not detectably affect integration at <it>AAVS1</it>, as measured by semi-quantitative nested PCR assays. Sequencing of integration junctions shows the joining of the modified ITRs to <it>AAVS1 </it>sequences.</p> <p>Conclusions</p> <p>The ability of these <it>AAVS1 </it>sequences to substitute for the AAV2 RRS and <it>trs </it>provides indirect evidence that the stable secondary structure encompassing the <it>trs </it>is part of the AAV2 packaging signal.</p

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open-reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were performed with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with MRI (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30±10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from 3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a three-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility

Repair at Single Targeted DNA Double-Strand Breaks in Pluripotent and Differentiated Human Cells

Differences in ex vivo cell culture conditions can drastically affect stem cell physiology. We sought to establish an assay for measuring the effects of chemical, environmental, and genetic manipulations on the precision of repair at a single DNA double-strand break (DSB) in pluripotent and somatic human cells. DSBs in mammalian cells are primarily repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). For the most part, previous studies of DSB repair in human cells have utilized nonspecific clastogens like ionizing radiation, which are highly nonphysiologic, or assayed repair at randomly integrated reporters. Measuring repair after random integration is potentially confounded by locus-specific effects on the efficiency and precision of repair. We show that the frequency of HR at a single DSB differs up to 20-fold between otherwise isogenic human embryonic stem cells (hESCs) based on the site of the DSB within the genome. To overcome locus-specific effects on DSB repair, we used zinc finger nucleases to efficiently target a DSB repair reporter to a safe-harbor locus in hESCs and a panel of somatic human cell lines. We demonstrate that repair at a targeted DSB is highly precise in hESCs, compared to either the somatic human cells or murine embryonic stem cells. Differentiation of hESCs harboring the targeted reporter into astrocytes reduces both the efficiency and precision of repair. Thus, the phenotype of repair at a single DSB can differ based on either the site of damage within the genome or the stage of cellular differentiation. Our approach to single DSB analysis has broad utility for defining the effects of genetic and environmental modifications on repair precision in pluripotent cells and their differentiated progeny