Dynamics of waves in 1D electron systems: Density oscillations driven by population inversion

We explore dynamics of a density pulse induced by a local quench in a one-dimensional electron system. The spectral curvature leads to an "overturn" (population inversion) of the wave. We show that beyond this time the density profile develops strong oscillations with a period much larger than the Fermi wave length. The effect is studied first for the case of free fermions by means of direct quantum simulations and via semiclassical analysis of the evolution of Wigner function. We demonstrate then that the period of oscillations is correctly reproduced by a hydrodynamic theory with an appropriate dispersive term. Finally, we explore the effect of different types of electron-electron interaction on the phenomenon. We show that sufficiently strong interaction [$U(r)\gg 1/mr^2$ where $m$ is the fermionic mass and $r$ the relevant spatial scale] determines the dominant dispersive term in the hydrodynamic equations. Hydrodynamic theory reveals crucial dependence of the density evolution on the relative sign of the interaction and the density perturbation.Comment: 20 pages, 13 figure

Clinical application of a cancer genomic profiling assay to guide precision medicine decisions

AIM: Develop and apply a comprehensive and accurate next-generation sequencing based assay to help clinicians to match oncology patients to therapies. MATERIALS and METHODS: The performance of the CANCERPLEX(R) assay was assessed using DNA from well-characterized routine clinical formalin-fixed paraffin-embedded (FFPE) specimens and cell lines. RESULTS: The maximum sensitivity of the assay is 99.5% and its accuracy is virtually 100% for detecting somatic alterations with an allele fraction of as low as 10%. Clinically actionable variants were identified in 93% of patients (930 of 1000) who underwent testing. CONCLUSION: The test\u27s capacity to determine all of the critical genetic changes, tumor mutation burden, microsatellite instability status and viral associations has important ramifications on clinical decision support strategies, including identification of patients who are likely to benefit from immune checkpoint blockage therapies

The Sec1/Munc18 protein Vps45 regulates cellular levels of its SNARE binding partners Tlg2 and Snc2 in Saccharomyces cerevisiae

Intracellular membrane trafficking pathways must be tightly regulated to ensure proper functioning of all eukaryotic cells. Central to membrane trafficking is the formation of specific SNARE (soluble N-ethylmeleimide-sensitive factor attachment protein receptor) complexes between proteins on opposing lipid bilayers. The Sec1/Munc18 (SM) family of proteins play an essential role in SNARE-mediated membrane fusion, and like the SNAREs are conserved through evolution from yeast to humans. The SM protein Vps45 is required for the formation of yeast endosomal SNARE complexes and is thus essential for traffic through the endosomal system. Here we report that, in addition to its role in regulating SNARE complex assembly, Vps45 regulates cellular levels of its SNARE binding partners: the syntaxin Tlg2 and the v-SNARE Snc2: Cells lacking Vps45 have reduced cellular levels of Tlg2 and Snc2; and elevation of Vps45 levels results in concomitant increases in the levels of both Tlg2 and Snc2. As well as regulating traffic through the endosomal system, the Snc v-SNAREs are also required for exocytosis. Unlike most vps mutants, cells lacking Vps45 display multiple growth phenotypes. Here we report that these can be reversed by selectively restoring Snc2 levels in vps45 mutant cells. Our data indicate that as well as functioning as part of the machinery that controls SNARE complex assembly, Vps45 also plays a key role in determining the levels of its cognate SNARE proteins; another key factor in regulation of membrane traffic

High Mutability of the Tumor Suppressor Genes RASSF1 and RBSP3 (CTDSPL) in Cancer

BACKGROUND:Many different genetic alterations are observed in cancer cells. Individual cancer genes display point mutations such as base changes, insertions and deletions that initiate and promote cancer growth and spread. Somatic hypermutation is a powerful mechanism for generation of different mutations. It was shown previously that somatic hypermutability of proto-oncogenes can induce development of lymphomas. METHODOLOGY/PRINCIPAL FINDINGS:We found an exceptionally high incidence of single-base mutations in the tumor suppressor genes RASSF1 and RBSP3 (CTDSPL) both located in 3p21.3 regions, LUCA and AP20 respectively. These regions contain clusters of tumor suppressor genes involved in multiple cancer types such as lung, kidney, breast, cervical, head and neck, nasopharyngeal, prostate and other carcinomas. Altogether in 144 sequenced RASSF1A clones (exons 1-2), 129 mutations were detected (mutation frequency, MF = 0.23 per 100 bp) and in 98 clones of exons 3-5 we found 146 mutations (MF = 0.29). In 85 sequenced RBSP3 clones, 89 mutations were found (MF = 0.10). The mutations were not cytidine-specific, as would be expected from alterations generated by AID/APOBEC family enzymes, and appeared de novo during cell proliferation. They diminished the ability of corresponding transgenes to suppress cell and tumor growth implying a loss of function. These high levels of somatic mutations were found both in cancer biopsies and cancer cell lines. CONCLUSIONS/SIGNIFICANCE:This is the first report of high frequencies of somatic mutations in RASSF1 and RBSP3 in different cancers suggesting it may underlay the mutator phenotype of cancer. Somatic hypermutations in tumor suppressor genes involved in major human malignancies offer a novel insight in cancer development, progression and spread

Hadron Energy Reconstruction for the ATLAS Calorimetry in the Framework of the Non-parametrical Method

This paper discusses hadron energy reconstruction for the ATLAS barrel prototype combined calorimeter (consisting of a lead-liquid argon electromagnetic part and an iron-scintillator hadronic part) in the framework of the non-parametrical method. The non-parametrical method utilizes only the known $e/h$ ratios and the electron calibration constants and does not require the determination of any parameters by a minimization technique. Thus, this technique lends itself to an easy use in a first level trigger. The reconstructed mean values of the hadron energies are within $\pm 1$ of the true values and the fractional energy resolution is $[(58\pm3)/\sqrt{E}+(2.5\pm0.3)$. The value of the $e/h$ ratio obtained for the electromagnetic compartment of the combined calorimeter is $1.74\pm0.04$ and agrees with the prediction that $e/h > 1.7$ for this electromagnetic calorimeter. Results of a study of the longitudinal hadronic shower development are also presented. The data have been taken in the H8 beam line of the CERN SPS using pions of energies from 10 to 300 GeV.Comment: 33 pages, 13 figures, Will be published in NIM

Работа Stroke team: опыт перевода пациентов с ишемическим инсультом на тромбэкстракцию из межрайонных больниц в Региональный сосудистый центр г. Красноярска

Modern high-technology methods for ischemic stroke treatment (systemic thrombolysis, mechanical thrombectomy, thrombaspiration, stenting of cerebral arteries) can improve the rehabilitation potential and survival of patients. Important tasks here are selection for reperfusion and its performance on the greatest possible number of peracute patients. Mechanical thrombectomy combined with systemic thrombolysis is the most effective reperfusion strategy in the therapeutic window, but the availability of endovascular methods is limited to highly specialized centres. One way to solve this problem is to organize effective logistics with stroke patients, which will provide high-tech care for patients living far from large treatment centers due to regulated interaction between institutions at different levels.The aim of the study was to improve emergency interaction related to transfer of peracute stroke patients from primary vascular units and district hospitals of the Krasnoyarsk region to Krasnoyarsk Regional Vascular Center for thrombectomy. Современные высокотехнологичные методы лечения ишемического инсульта (системный тромболизис, механическая тромбэкстракция, тромбаспирация, стентирование церебральных сосудов) позволяют улучшить реабилитационный потенциал и выживаемость пациентов. Важной задачей является отбор и проведение реперфузии в острейшем периоде наибольшему количеству больных. Тромбэкстракция в сочетании с системным тромболизисом является наиболее эффективной стратегией реперфузии в терапевтическом окне, однако доступность эндоваскулярных методов ограничена высокоспециализированными центрами. Одним из путей решения этой задачи является организация эффективной логистики пациентов с острым нарушением мозгового кровообращения (ОНМК), что позволит оказывать высокотехнологичную помощь пациентам, проживающим на удалении от крупных лечебных центров, благодаря отрегулированному взаимодействию между учреждениями разного уровня.Цель исследования: совершенствование экстренного взаимодействия по вопросам перевода пациентов в острейшем периоде ишемического инсульта из первичных сосудистых отделений и межрайонных больниц Красноярского края в Региональный сосудистый центр г. Красноярска для проведения тромбэкстракции.

Analysis of SEC9 Suppression Reveals a Relationship of SNARE Function to Cell Physiology

BACKGROUND:Growth and division of Saccharomyces cerevisiae is dependent on the action of SNARE proteins that are required for membrane fusion. SNAREs are regulated, through a poorly understood mechanism, to ensure membrane fusion at the correct time and place within a cell. Although fusion of secretory vesicles with the plasma membrane is important for yeast cell growth, the relationship between exocytic SNAREs and cell physiology has not been established. METHODOLOGY/PRINCIPAL FINDINGS:Using genetic analysis, we identified several influences on the function of exocytic SNAREs. Genetic disruption of the V-ATPase, but not vacuolar proteolysis, can suppress two different temperature-sensitive mutations in SEC9. Suppression is unlikely due to increased SNARE complex formation because increasing SNARE complex formation, through overexpression of SRO7, does not result in suppression. We also observed suppression of sec9 mutations by growth on alkaline media or on a non-fermentable carbon source, conditions associated with a reduced growth rate of wild-type cells and decreased SNARE complex formation. CONCLUSIONS/SIGNIFICANCE:Three main conclusions arise from our results. First, there is a genetic interaction between SEC9 and the V-ATPase, although it is unlikely that this interaction has functional significance with respect to membrane fusion or SNAREs. Second, Sro7p acts to promote SNARE complex formation. Finally, Sec9p function and SNARE complex formation are tightly coupled to the physiological state of the cell