117 research outputs found

    Efficient Numerical Methods to Solve Sparse Linear Equations with Application to PageRank

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    In this paper, we propose three methods to solve the PageRank problem for the transition matrices with both row and column sparsity. Our methods reduce the PageRank problem to the convex optimization problem over the simplex. The first algorithm is based on the gradient descent in L1 norm instead of the Euclidean one. The second algorithm extends the Frank-Wolfe to support sparse gradient updates. The third algorithm stands for the mirror descent algorithm with a randomized projection. We proof converges rates for these methods for sparse problems as well as numerical experiments support their effectiveness.Comment: 26 page

    Cómo reconciliar la pesca y la protección de hábitats en áreas marinas protegidas de Rumanía

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    The extension of the Natura 2000 European ecological network to the Romanian marine territory (1 site according to the Birds Directive requirements and eight sites according to the Habitats Directive requirements, one also being a natural reserve and one part of the Danube Delta Biosphere Reserve) might cause conflicts between the Romanian marine fishery and these sites. In order to minimize such conflicts, the evaluation of the interaction between fishery and the preservation objectives of the Natura 2000 sites is compulsory and extremely important. The assessment of the environmental impact is a key tool of the EU environmental legislation, which is used in evaluating the effect of human activities on the ecosystem. In addition, the involvement of all interested stakeholders in the development of the fishery on the Romanian littoral and in environmental protection will be the key to success in finding viable co-management solutions in the Natura 2000 sites. The present paper aims to examine how the fisheries interact with the marine environment on the Romanian coast in the network of marine protected areas.La extensión de la red de trabajo ecológica europea Natura 2000 en el territorio marino de Rumanía (1 lugar según los requisitos de la Directiva de aves y 8 lugares según los requisitos de la Directiva de Hábitats, siendo también uno de ellos una reserva natural y una parte de la Reserva de Biosfera del Delta del Danubio) podría causar conflictos entre las pesquerías marinas rumanas y estos lugares. Para minimizar estos conflictos, es obligatorio y extremadamente importante llevar a cabo la evaluación de la interacción entre la pesca y los objetivos de preservación de los lugares de la red Natura 2000. La evaluación del impacto ambiental es una herramienta clave de la legislación ambiental europea, que se utiliza en la evaluación del efecto de las actividades antropogénicas en el ecosistema. Además, la participación de todos los actores interesados en el desarrollo de las pesquerías del litoral rumano y en la protección ambiental, servirá para demostrar la viabilidad de las soluciones alcanzadas a través de la cogestión en los lugares de la red Natura 2000. El presente documento tiene como objeto examinar como interaccionan las pesquerías con el medio marino en la costa de Rumanía dentro del sistema de Áreas Marinas Protegidas

    Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates spontaneous neurotransmitter release

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    Central synapses exhibit spontaneous neurotransmitter release that is selectively regulated by cAMP-dependent protein kinase A (PKA). We now show that synaptic vesicles contain synaptotagmin-12, a synaptotagmin isoform that differs from classical synaptotagmins in that it does not bind Ca2+. In synaptic vesicles, synaptotagmin-12 forms a complex with synaptotagmin-1 that prevents synaptotagmin-1 from interacting with SNARE complexes. We demonstrate that synaptotagmin-12 is phosphorylated by cAMP-dependent PKA on serine97, and show that expression of synaptotagmin-12 in neurons increases spontaneous neurotransmitter release by approximately threefold, but has no effect on evoked release. Replacing serine97 by alanine abolishes synaptotagmin-12 phosphorylation and blocks its effect on spontaneous release. Our data suggest that spontaneous synaptic-vesicle exocytosis is selectively modulated by a Ca2+-independent synaptotagmin isoform, synaptotagmin-12, which is controlled by cAMP-dependent phosphorylation

    The CAMKK2-AMPK kinase pathway mediates the synaptotoxic effects of Aβ oligomers through Tau phosphorylation

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    Amyloid-β 1-42 (Aβ42) oligomers are synaptotoxic for excitatory cortical and hippocampal neurons and might play a role in early stages of Alzheimer's disease (AD) progression. Recent results suggested that Aβ42 oligomers trigger activation of AMP-activated kinase (AMPK), and its activation is increased in the brain of patients with AD. We show that increased intracellular calcium [Ca²⁺](i) induced by NMDA receptor activation or membrane depolarization activates AMPK in a CAMKK2-dependent manner. CAMKK2 or AMPK overactivation is sufficient to induce dendritic spine loss. Conversely, inhibiting their activity protects hippocampal neurons against synaptotoxic effects of Aβ42 oligomers in vitro and against the loss of dendritic spines observed in the human APP(SWE,IND)-expressing transgenic mouse model in vivo. AMPK phosphorylates Tau on KxGS motif S262, and expression of Tau S262A inhibits the synaptotoxic effects of Aβ42 oligomers. Our results identify a CAMKK2-AMPK-Tau pathway as a critical mediator of the synaptotoxic effects of Aβ42 oligomers

    Sorption analysis of composites based on zinc oxide for catalysis and medical materials science

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    Modified structures based on zinc oxide are of special interest in catalysis and medicine. The work discusses the composite structures based on zinc oxide and hydroxyapatite, as well as silver-modified zinc oxide nanostructures obtained by chemical deposition. The obtained materials were studied using a Rigaku SmartLab diffractometric complex and a Sorbi MS sorption analyzer. The specific surface area was studied and the average size of nanoparticles in the samples is determined. The application scope of the considered materials was catalysis and medicine, including the use in bone engineering as bioactive coatings deposited on the surface of a metal bioimplant

    Исследование эффективности работы центробежно-ударного измельчителя фуражного зерна новой конструкции

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    Crushing feed grain involves hammer crushers, which are characterized by high specific energy consumption and its uneven fractional composition. It is possible to obtain high-quality shredded grain with less energy when using a centrifugal-impact crusher of the new design with a hole in the loading neck to supply the chopping chamber with additional air at a rate of up to 4.8 m/s. An additional hole provides a 1.8...13-time increase in the airspeed through the unloading neck when the rotor’s rotation frequency changes from 3,750 to 2,250 min–1, thereby enabling the timely evacuation of the shredded material from the crusher.The regression equations have been derived to determine the structural and regime parameters of the shredder, which ensure the maximal performance and minimal unit energy costs. The greatest impact on crusher productivity is exerted by the diameter of the sieve holes and the area of the bunker’s unloading window. The greatest effect on the specific energy intensity of the grinding process is exerted by the diameter of the sieve holes. The maximal performance of the crusher, 1,440 kg/h, and the minimal energy capacity, taking into consideration the achieved grinding degree, of 2.1 W∙s/(kg∙grinding degree unit), are observed when using a sieve with the holes’ diameter of 7 mm, the rotor’s rotation frequency of 3,500 min–1, and the maximally open unloading window of the bunker, at F=1.458 m2·10–3. The specific energy consumption for chopping barley is less by 1.22...1.89 times than that of the hammer crushers RVO 35, DB-5, KD-2A. The dust-like fraction is less than 5.74 %, which is half the amount of the hammer crusher DM-6. The rational crusher operation modes have been determined in order to prepare feed grain for feeding farm animals of different species and agesДля измельчения фуражного зерна используют молотковые дробилки, которым свойственны высокий удельный расход энергии и его неравномерный фракционный состав. Получение качественно измельченного зерна с меньшими энергозатратами возможно на центробежно-ударном измельчителе новой конструкции с отверстием в загрузочной горловине для дополнительной подачи воздуха в камеру измельчения со скоростью до 4,8 м/с. Дополнительное отверстие обеспечивает повышение скорости воздуха в выгрузной горловине в 1,8…13 раз при изменении частоты вращения ротора с 3750 до 2250 мин-1, своевременную эвакуацию измельченного материала из измельчителя.Получены уравнения регрессии, позволяющие определить конструкционные и режимные параметры измельчителя, обеспечивающие максимум производительности и минимум удельных энергозатрат. Наибольшее влияние на производительность измельчителя оказывают диаметр отверстий решет и площадь выгрузного окна бункера. Наибольшее влияние на удельную энергоемкость процесса измельчения оказывает диаметр отверстий решета. Максимальная производительность измельчителя – 1440 кг/ч и минимальная энергоёмкость с учетом достигнутой степени измельчения 2,1 Вт∙с/(кг∙ед.ст.изм.) наблюдается при использовании решета с диаметром отверстий 7 мм, частоте вращения ротора 3500 мин-1 имаксимально открытом выгрузном окне бункера при F=1,458 м2·10-3. Удельный расход энергии на измельчение ячменя меньше в 1,22…1,89 раза, чем у молотковых дробилок RVO 35, ДБ-5, КД-2А. Содержание пылевидной фракции составляет менее 5,74 %, что в 2 раза меньше, по сравнению с молотковой дробилкой ДЗМ-6. Определены рациональные режимы работы измельчителя для подготовки фуражного зерна к скармливанию для сельскохозяйственных животных различных видов и возрасто

    High frequency of BRCA1, but not CHEK2 or NBS1 (NBN), founder mutations in Russian ovarian cancer patients

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    <p>Abstract</p> <p>Background</p> <p>A significant portion of ovarian cancer (OC) cases is caused by germ-line mutations in BRCA1 or BRCA2 genes. BRCA testing is cheap in populations with founder effect and therefore recommended for all patients with OC diagnosis. Recurrent mutations constitute the vast majority of BRCA defects in Russia, however their impact in OC morbidity has not been yet systematically studied. Furthermore, Russian population is characterized by a relatively high frequency of CHEK2 and NBS1 (NBN) heterozygotes, but it remains unclear whether these two genes contribute to the OC risk.</p> <p>Methods</p> <p>The study included 354 OC patients from 2 distinct, geographically remote regions (290 from North-Western Russia (St.-Petersburg) and 64 from the south of the country (Krasnodar)). DNA samples were tested by allele-specific PCR for the presence of 8 founder mutations (BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT, CHEK2 1100delC, CHEK2 IVS2+1G>A, NBS1 657del5). In addition, literature data on the occurrence of BRCA1, BRCA2, CHEK2 and NBS1 mutations in non-selected ovarian cancer patients were reviewed.</p> <p>Results</p> <p>BRCA1 5382insC allele was detected in 28/290 (9.7%) OC cases from the North-West and 11/64 (17.2%) OC patients from the South of Russia. In addition, 4 BRCA1 185delAG, 2 BRCA1 4153delA, 1 BRCA2 6174delT, 2 CHEK2 1100delC and 1 NBS1 657del5 mutation were detected. 1 patient from Krasnodar was heterozygous for both BRCA1 5382insC and NBS1 657del5 variants.</p> <p>Conclusion</p> <p>Founder BRCA1 mutations, especially BRCA1 5382insC variant, are responsible for substantial share of OC morbidity in Russia, therefore DNA testing has to be considered for every OC patient of Russian origin. Taken together with literature data, this study does not support the contribution of CHEK2 in OC risk, while the role of NBS1 heterozygosity may require further clarification.</p
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