Study of hybrid Х pinches in different conditions

A standard X-pinch consists of two or more fine wires that cross at a single point as the load of a pulsed power generator. To simplify the X-pinch load, a hybrid configuration consisting of solid conical electrodes connected by a wire, has been suggested and tested on four generators ranging in current from 200 kA to 1 MA and risetimes varying from 45 to 170 ns. The experiments have shown that for each generator, a wire material, diameter and length can be found for which the X-pinches generate a single intense burst of soft x-rays and develop a single hot spot. Also they generated less hard x-ray intensity than that measured in comparable standard X-pinches.Стандартные Х-пинчи состоят из двух или более проволочек, перекрещенных в диоде сильноточного генератора. Чтобы упростить конфигурацию Х-пинчей, была предложена и протестирована на четырех сильноточных генераторах с токами от 200 кА до 1 МА и временем нарастания импульса от 45 до 170 нс нагрузка в виде гибридного Х-пинча. Гибридные Х-пинчи состоят из двух твердотельных тугоплавких электродов, соединенных проволочкой. Проведенные эксперименты показали, что для каждого генератора можно подобрать материал проволочки, диаметр и длину, при которых гибридные Х-пинчи образуют единичную горячую точку и излучают интенсивную вспышку мягкого рентгеновского излучения. При этом зарегистрированный уровень жесткого рентгеновского излучения был значительно ниже, чем в стандартных Х-пинчах.Стандартні Х-пінчі складаються з двох або більше дротиків, перехрещених у діоді потужнострумового генератора. Щоб спростити конфігурацію Х-пінча, була запропонована і протестована на чотирьох потужнострумових генераторах із струмами від 200 кА до 1 МА та часом наростання імпульсу від 45 до 170 нс навантаження у вигляді гібридного Х-пінча. Гібридні Х-пінчі складаються з двох твердотільних тугоплавких електродів, з'єднаних дротиком. Проведені експерименти показали, що для кожного генератора можна підібрати матеріал дротика, діаметр і довжину, при яких гібридні Х-пінчі утворюють одиничну гарячу краплю та випромінюють інтенсивний спалах м'якого рентгенівського випромінювання. При цьому зареєстрований рівень жорсткого рентгенівського випромінювання був значно нижче, ніж у стандартних Х-пінчах

Research is needed to inform environmental management of hydrothermally inactive and extinct polymetallic sulfide (PMS) deposits

Polymetallic sulfide (PMS) deposits produced at hydrothermal vents in the deep sea are of potential interest to miners. Hydrothermally active sulfide ecosystems are valued for the extraordinary chemosynthetic communities that they support. Many countries, including Canada, Portugal, and the United States, protect vent ecosystems in their Exclusive Economic Zones. When hydrothermal activity ceases temporarily (dormancy) or permanently (extinction), the habitat and associated ecosystem change dramatically. Until recently, so-called "inactive sulfide" habitats, either dormant or extinct, received little attention from biologists. However, the need for environmental management of deep-sea mining places new imperatives for building scientific understanding of the structure and function of inactive PMS deposits. This paper calls for actions of the scientific community and the emergent seabed mining industry to i) undertake fundamental ecological descriptions and study of ecosystem functions and services associated with hydrothermally inactive PMS deposits, ii) evaluate potential environmental risks to ecosystems of inactive PMS deposits through research, and iii) identify environmental management needs that may enable mining of inactive PMS deposits. Mining of some extinct PMS deposits may have reduced environmental risk compared to other seabed mining activities, but this must be validated through scientific research on a case-by-case basis.FCT: IF/00029/2014/CP1230/CT0002/ UID/05634/2020/ CEECIND005262017/ UID/MAR/00350/2019; Direcao-Geral de Politica do Mar (DGPM) Mining2/2017/005/ Mining2/2017/001info:eu-repo/semantics/publishedVersio

Comprehensive lung injury pathology induced by mTOR inhibitors

Molecular Targets in Oncology[Abstract] Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibro-proliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall cascade hypothesis of interstitial lung diseases that represents a common, partly underlying synergism among them as well as the lung pathogenesis side effects of mammalian target of rapamycin inhibitors

Distinct Chromosome Segregation Roles for Spindle Checkpoint Proteins

The spindle checkpoint plays a central role in the fidelity of chromosome transmission by ensuring that anaphase is initiated only after kinetochore-microtubule associations of all sister chromatid pairs are complete. In this study, we find that known spindle checkpoint proteins do not contribute equally to chromosome segregation fidelity in Saccharomyces cerevisiae. Loss of Bub1 or Bub3 protein elicits the largest effect. Analysis of Bub1p reveals the presence of two molecular functions. An N-terminal 608-amino acid (nonkinase) portion of the protein supports robust checkpoint activity, and, as expected, contributes to chromosome segregation. A C-terminal kinase-encoding segment independently contributes to chromosome segregation through an unknown mechanism. Both molecular functions depend on association with Bub3p. A 156-amino acid fragment of Bub1p functions in Bub3p binding and in kinetochore localization by one-hybrid assay. An adjacent segment is required for Mad1p binding, detected by deletion analysis and coimmunoprecipitation. Finally, overexpression of wild-type BUB1 or MAD3 genes leads to chromosome instability. Analysis of this activity indicates that the Bub3p-binding domain of Bub1p contributes to this phenotype through disruption of checkpoint activity as well as through introduction of kinetochore or spindle damage

Spindle Checkpoint Requires Mad1-bound and Mad1-free Mad2

The spindle checkpoint prevents anaphase from occurring until all chromosomes have attached properly to the mitotic spindle. The checkpoint components Mad1 and Mad2 associate with unattached kinetochores and are probably involved in triggering the checkpoint. We now demonstrate that in Xenopus egg extracts Mad1 and Mad2 form a stable complex, whereas a fraction of Mad2 molecules is not bound to Mad1. The checkpoint establishment and maintenance are lost upon titrating out free Mad2 with an excess of Mad1 or a truncated Mad1 (amino acids 326–718, Mad1C) that contains the Mad2-binding region. Mad1N (amino acids 1–445) that binds kinetochores, but not Mad2, reduces Mad1 and Mad2 at kinetochores and abolishes checkpoint maintenance. Furthermore, the association between Mad2 and Cdc20, the activator for the anaphase-promoting complex, is enhanced under checkpoint-active condition compared with that at metaphase. Immunodepletion analysis shows that the Mad1-free Mad2 protein is unable to bind Cdc20, consistent with the model that kinetochore localization of Mad2 facilitates the formation of Mad2–Cdc20 complex. This study demonstrates that the ratio between Mad1 and Mad2 is critical for maintaining a pool of Mad1-free Mad2 that is necessary for the spindle checkpoint. We propose that Mad2 may become activated and dissociated from Mad1 at kinetochores and is replenished by the pool of Mad1-free Mad2

Checkpoint Protein BubR1 Acts Synergistically with Mad2 to Inhibit Anaphase-promoting Complex

The spindle assembly checkpoint monitors the attachment of kinetochores to the mitotic spindle and the tension exerted on kinetochores by microtubules and delays the onset of anaphase until all the chromosomes are aligned at the metaphase plate. The target of the checkpoint control is the anaphase-promoting complex (APC)/cyclosome, a ubiquitin ligase whose activation by Cdc20 is required for separation of sister chromatids. In response to activation of the checkpoint, Mad2 binds to and inhibits Cdc20-APC. I show herein that in checkpoint-arrested cells, human Cdc20 forms two separate, inactive complexes, a lower affinity complex with Mad2 and a higher affinity complex with BubR1. Purified BubR1 binds to recombinant Cdc20 and this interaction is direct. Binding of BubR1 to Cdc20 inhibits activation of APC and this inhibition is independent of its kinase activity. Quantitative analysis indicates that BubR1 is 12-fold more potent than Mad2 as an inhibitor of Cdc20. Although at high protein concentrations BubR1 and Mad2 each is sufficient to inhibit Cdc20, BubR1 and Mad2 mutually promote each other's binding to Cdc20 and function synergistically at physiological concentrations to quantitatively inhibit Cdc20-APC. Thus, BubR1 and Mad2 act cooperatively to prevent premature separation of sister chromatids by directly inhibiting APC