Vacancy complexes in nonequilibrium germanium-tin semiconductors

Understanding the nature and behavior of vacancy-like defects in epitaxial GeSn metastable alloys is crucial to elucidate the structural and optoelectronic properties of these emerging semiconductors. The formation of vacancies and their complexes is expected to be promoted by the relatively low substrate temperature required for the epitaxial growth of GeSn layers with Sn contents significantly above the equilibrium solubility of 1 at.%. These defects can impact both the microstructure and charge carrier lifetime. Herein, to identify the vacancy-related complexes and probe their evolution as a function of Sn content, depth-profiled pulsed low-energy positron annihilation lifetime spectroscopy and Doppler broadening spectroscopy were combined to investigate GeSn epitaxial layers with Sn content in the 6.5-13.0 at.% range. The samples were grown by chemical vapor deposition method at temperatures between 300 and 330 {\deg}C. Regardless of the Sn content, all GeSn samples showed the same depth-dependent increase in the positron annihilation line broadening parameters, which confirmed the presence of open volume defects. The measured average positron lifetimes were the highest (380-395 ps) in the region near the surface and monotonically decrease across the analyzed thickness, but remain above 350 ps. All GeSn layers exhibit lifetimes that are 85 to 110 ps higher than the Ge reference layers. Surprisingly, these lifetimes were found to decrease as Sn content increases in GeSn layers. These measurements indicate that divacancies are the dominant defect in the as-grown GeSn layers. However, their corresponding lifetime was found to be shorter than in epitaxial Ge thus suggesting that the presence of Sn may alter the structure of divacancies. Additionally, GeSn layers were found to also contain a small fraction of vacancy clusters, which become less important as Sn content increases

Preferential binding of ATR protein to UV-damaged DNA

The ATR protein is a member of the phosphoinositide 3-kinase-related kinase family and plays an important role in UV-induced DNA damage checkpoint response. Its role as a signal transducer in cell cycle checkpoint is well established, but it is currently unclear whether ATR functions as a damage sensor as well. Here we have purified the ATR protein and investigated its interaction with DNA by using biochemical analysis and electron microscopy. We find that ATR is a DNA-binding protein with higher affinity to UV-damaged than undamaged DNA. In addition, damaged DNA stimulates the kinase activity of ATR to a significantly higher level than undamaged DNA. Our data suggest that ATR may function as an initial sensor in the DNA damage checkpoint response

Coronin 1B Antagonizes Cortactin and Remodels Arp2/3-Containing Actin Branches in Lamellipodia

The dendritic actin network generated by Arp2/3 complex in lamellipodia underlies formation of protrusions, directional sensing and migration. While the generation of this network is well studied, the mechanisms regulating network disassembly are poorly understood. We report that Coronin 1B disassembles Arp2/3-containing actin filament branches by inducing Arp2/3 dissociation. This activity is antagonized by Cortactin, a filament branch stabilizer. Consistent with this biochemical competition, depletion of both proteins partially rescues defects in lamellipodial dynamics observed upon depletion of either protein alone. Coronin 1B targets actin branches in a manner that is mutually exclusive with Arp2/3 complex and alters the branch angle. We conclude that Coronin 1B replaces Arp2/3 complex at actin filament branches as the dendritic network matures and drives the turnover of branched actin networks

Dynamic processes happening during the evaporation of films of fusible materials

Optical waveguides on glass substrates are a promising area in their application in simple and cheap optoelectronic devices. As shown in [1], the highest refractive index is achieved during the formation of waveguides by oxidized film diffusion. However, realization of a number of electro-optical effects is restrained by probabilistic repeatability of wave guiding layers which holds down the development of optoelectronics [1-3]. This happens due to the fact that film formation in gas exchange mode isn't explored enough. One of the reasons of probabilistic repeatability of local thickness and film composition is dynamic processes which happen during the material evaporation. The regularities of evaporation, which were earlier found by Knudsen, Langmuir and other scientists for point sources, fail when it comes to the line where one material escape into another state. Most materials, which have three states - solid, liquid, gaseous - at ambient pressure heating, in vacuum, lose their liquid state partly or completely. Moreover, the film distribution over the substrate is quite unclear because of the poor study of molecular vapor flow and substrate interaction

Ultrasound examination with contrast in the diagnosis of inflammatory bowel disease. The results of the pilot study

Aim. Assessment of diagnostic significance of informativeness and security of ultrasonography with contrast enhancement drug SonoVue in the diagnosis of Crohn's disease (CD) and ulcerative colitis (UC). Materials and methods. The pilot conducted a prospective study which involved 15 patients with inflammatory bowel disease (IBD). All patients gave written consent to participate in the study and processing of personal data. The study included adult patients with an established diagnosis of UC and CD, with proven clinical activity of the disease. Activity was evaluated based on clinical and laboratory data on the scale of best (CDAI >150) for patients with CD and on a scale of Trulove-Witts (2-3 stage) and the Mayo index (DAI) for patients with UC. All the patients underwent colonoscopy with biopsy, ultrasound examination of abdominal cavity organs with the study of the vascularization of the intestinal wall (color Doppler, power Doppler, contrast study). Results. The use of contrast showed additional features in the instrumental evaluation of activity of inflammatory process, identification of complications and assessment of prognosis. Conclusion. The results of ultrasound of the bowel with contrast can be used to assess the activity and stage of disease in patients with UC or CD

ИССЛЕДОВАНИЕ СТРУКТУРЫ И ФАЗОВОГО СОСТАВАПОРОШКОВЫХ АЛЮМОФОСФОРИСТЫХ ЛИГАТУР

There were developed powder aluminium-phosphorus master alloys for modification of hypereutectic silumins. There was se-lected the best performance processing of powder mixes in the high-energy planetary mill that ensured minimum losses of feed stock and microstructure with uniform and disperse distribution of the proeutectoid constituents’ particles in aluminium matrix. By means of X-ray diffraction study was investigated phase composition of obtained master alloys. There was demonstrated high efficiency of the modification of hypereutectic silumins Al–17wt.%Si by alloying of phosphorus (0,008 wt.%) obtained master alloys.Разработаны порошковые алюмофосфористые лигатуры для модифицирования заэвтектических силуминов. Выбраны оптимальные режимы обработки порошковых смесей в высокоэнергетической планетарной мельнице, обеспечивающие минимальные потери исходного материала и микроструктуру с однородным и дисперсным распределением в алюминиевой матрице частиц избыточных фаз. Методом микрорентгеноспектрального анализа исследован фазовый состав полученных лигатур. Показана высокая эффективность модифицирования заэвтектического силумина Al–17мас.%Si введением фосфора (0,008 мас.%) полученными лигатурами

Effects of preset sequential administrations of sunitinib and everolimus on tumour differentiation in Caki-1 renal cell carcinoma.

BACKGROUND: Sunitinib (VEGFR/PDGFR inhibitor) and everolimus (mTOR inhibitor) are both approved for advanced renal cell carcinoma (RCC) as first-line and second-line therapy, respectively. In the clinics, sunitinib treatment is limited by the emergence of acquired resistance, leading to a switch to second-line treatment at progression, often based on everolimus. No data have been yet generated on programmed alternating sequential strategies combining alternative use of sunitinib and everolimus before progression. Such strategy is expected to delay the emergence of acquired resistance and improve tumour control. The aim of our study was to assess the changes in tumours induced by three different sequences administration of sunitinib and everolimus. METHODS: In human Caki-1 RCC xenograft model, sunitinib was alternated with everolimus every week, every 2 weeks, or every 3 weeks. Effects on necrosis, hypoxia, angiogenesis, and EMT status were assessed by immunohisochemistry and immunofluorescence. RESULTS: Sunitinib and everolimus programmed sequential regimens before progression yielded longer median time to tumour progression than sunitinib and everolimus monotherapies. In each group of treatment, tumour growth control was associated with inhibition of mTOR pathway and changes from a mesenchymal towards an epithelial phenotype, with a decrease in vimentin and an increase in E-cadherin expression. The sequential combinations of these two agents in a RCC mouse clinical trial induced antiangiogenic effects, leading to tumour necrosis. CONCLUSIONS: In summary, our study showed that alternate sequence of sunitinib and everolimus mitigated the development of mesenchymal phenotype compared with sunitinib as single agent

Paleo-Immunology: Evidence Consistent with Insertion of a Primordial Herpes Virus-Like Element in the Origins of Acquired Immunity

BACKGROUND:The RAG encoded proteins, RAG-1 and RAG-2 regulate site-specific recombination events in somatic immune B- and T-lymphocytes to generate the acquired immune repertoire. Catalytic activities of the RAG proteins are related to the recombinase functions of a pre-existing mobile DNA element in the DDE recombinase/RNAse H family, sometimes termed the "RAG transposon". METHODOLOGY/PRINCIPAL FINDINGS:Novel to this work is the suggestion that the DDE recombinase responsible for the origins of acquired immunity was encoded by a primordial herpes virus, rather than a "RAG transposon." A subsequent "arms race" between immunity to herpes infection and the immune system obscured primary amino acid similarities between herpes and immune system proteins but preserved regulatory, structural and functional similarities between the respective recombinase proteins. In support of this hypothesis, evidence is reviewed from previous published data that a modern herpes virus protein family with properties of a viral recombinase is co-regulated with both RAG-1 and RAG-2 by closely linked cis-acting co-regulatory sequences. Structural and functional similarity is also reviewed between the putative herpes recombinase and both DDE site of the RAG-1 protein and another DDE/RNAse H family nuclease, the Argonaute protein component of RISC (RNA induced silencing complex). CONCLUSIONS/SIGNIFICANCE:A "co-regulatory" model of the origins of V(D)J recombination and the acquired immune system can account for the observed linked genomic structure of RAG-1 and RAG-2 in non-vertebrate organisms such as the sea urchin that lack an acquired immune system and V(D)J recombination. Initially the regulated expression of a viral recombinase in immune cells may have been positively selected by its ability to stimulate innate immunity to herpes virus infection rather than V(D)J recombination Unlike the "RAG-transposon" hypothesis, the proposed model can be readily tested by comparative functional analysis of herpes virus replication and V(D)J recombination

The Enterovirus 71 A-particle Forms a Gateway to Allow Genome Release: A CryoEM Study of Picornavirus Uncoating

Since its discovery in 1969, enterovirus 71 (EV71) has emerged as a serious worldwide health threat. This human pathogen of the picornavirus family causes hand, foot, and mouth disease, and also has the capacity to invade the central nervous system to cause severe disease and death. Upon binding to a host receptor on the cell surface, the virus begins a two-step uncoating process, first forming an expanded, altered "A-particle", which is primed for genome release. In a second step after endocytosis, an unknown trigger leads to RNA expulsion, generating an intact, empty capsid. Cryo-electron microscopy reconstructions of these two capsid states provide insight into the mechanics of genome release. The EV71 A-particle capsid interacts with the genome near the icosahedral two-fold axis of symmetry, which opens to the external environment via a channel ~10 Å in diameter that is lined with patches of negatively charged residues. After the EV71 genome has been released, the two-fold channel shrinks, though the overall capsid dimensions are conserved. These structural characteristics identify the two-fold channel as the site where a gateway forms and regulates the process of genome release. © 2013 Shingler et al

FHA-Mediated Cell-Substrate and Cell-Cell Adhesions Are Critical for Bordetella pertussis Biofilm Formation on Abiotic Surfaces and in the Mouse Nose and the Trachea

Bordetella spp. form biofilms in the mouse nasopharynx, thereby providing a potential mechanism for establishing chronic infections in humans and animals. Filamentous hemagglutinin (FHA) is a major virulence factor of B. pertussis, the causative agent of the highly transmissible and infectious disease, pertussis. In this study, we dissected the role of FHA in the distinct biofilm developmental stages of B. pertussis on abiotic substrates and in the respiratory tract by employing a murine model of respiratory biofilms. Our results show that the lack of FHA reduced attachment and decreased accumulation of biofilm biomass on artificial surfaces. FHA contributes to biofilm development by promoting the formation of microcolonies. Absence of FHA from B. pertussis or antibody-mediated blockade of surface-associated FHA impaired the attachment of bacteria to the biofilm community. Exogenous addition of FHA resulted in a dose-dependent inhibitory effect on bacterial association with the biofilms. Furthermore, we show that FHA is important for the structural integrity of biofilms formed on the mouse nose and trachea. Together, these results strongly support the hypothesis that FHA promotes the formation and maintenance of biofilms by mediating cell-substrate and inter-bacterial adhesions. These discoveries highlight FHA as a key factor in establishing structured biofilm communities in the respiratory tract