Ichthyosen: Pathophysiologische Modelle der epidermalen Differenzierung

Zusammenfassung: Die Ichthyosen sind eine durch Schuppung oder Keratosen charakterisierte heterogene Krankheitsgruppe monogenetisch vererbter Verhornungsstörungen. In der Vergangenheit wurden sie aufgrund klinischer Zeichen und des Vererbungsmusters nosologisch eingeteilt. Als Folge des massiven Wissenssprunges im Gebiet der molekularen Genetik wurden nun zahlreiche Gendefekte im Gebiet der Ichthyosen aufgeklärt. Dadurch trat die Komplexität der Ichthyosen zutage, wobei ähnliche oder gleiche Phänotypen durch Mutationen in verschiedenen Genen verursacht werden können, währenddessen umgekehrt einzelne Gene in verschiedenen, zum Teil stark divergierenden Phänotypen resultieren können. Daher wurde eine neue Klassifizierung notwendig, die klinische und neue molekulargenetische Erkenntnisse berücksichtigt und vereint. In dieser Publikation folgen wir größtenteils der Einteilung, die anlässlich der ersten Ichthyosis Consensus Conference in Sorèze, Frankreich, festgelegt wurd

TRAIP is a regulator of the spindle assembly checkpoint.

Accurate chromosome segregation during mitosis is temporally and spatially coordinated by fidelity-monitoring checkpoint systems. Deficiencies in these checkpoint systems can lead to chromosome segregation errors and aneuploidy, and promote tumorigenesis. Here, we report that the TRAF-interacting protein (TRAIP), a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation, is localized close to mitotic chromosomes. Its knockdown in HeLa cells by RNA interference (RNAi) decreased the time of early mitosis progression from nuclear envelope breakdown (NEB) to anaphase onset and increased the percentages of chromosome alignment defects in metaphase and lagging chromosomes in anaphase compared with those of control cells. The decrease in progression time was corrected by the expression of wild-type but not a ubiquitin-ligase-deficient form of TRAIP. TRAIP-depleted cells bypassed taxol-induced mitotic arrest and displayed significantly reduced kinetochore levels of MAD2 (also known as MAD2L1) but not of other spindle checkpoint proteins in the presence of nocodazole. These results imply that TRAIP regulates the spindle assembly checkpoint, MAD2 abundance at kinetochores and the accurate cellular distribution of chromosomes. The TRAIP ubiquitin ligase activity is functionally required for the spindle assembly checkpoint control

Late-Onset Multiple Self-Healing Squamous Epithelioma Ferguson-Smith Recurrence Induced by Radiotherapy.

We report the case of a woman in her 60s with confirmed multiple self-healing squamous epitheliomas (MSSE) Ferguson-Smith. After recurrences following surgery and radiotherapy, the patient was successfully treated with minimal surgical intervention combined with intralesional injections of triamcinolone acetate. The histological comparison between mature and regressed keratoacanthomas (KA) revealed an increased inflammatory infiltrate with numerous plasmacytoid dendritic cells in the regressed KA in comparison to the mature one, speaking in favor of an inflammation-mediated regression process. Corticosteroids injection in MSSE may have paradoxical effects with action on the proliferation phase rather than the inflammatory regression phase of the KA. Our case confirms previous reports showing that radiotherapy may exacerbate MSSE and should be avoided. Intralesional triamcinolone acetate injection is a safe and easy to use method also effective for multiple lesions. Our case underlines the difference between squamous cell carcinoma and KA, responding differently to therapies like imiquimod or radiotherapy

Разработка способов, алгоритмов и программ обнаружения и исправления пакетных или независимых ошибок при передаче данных по каналам связи

Настоящая научно-квалификационная работа посвящена разработке способов, алгоритмов и программ обнаружения и исправления ошибок при передаче данных по каналам связи для обеспечения целостности и надёжности передаваемых команд и данных между устройствами вычислительно техники, а также при считывании данных из запоминающих устройств.The present scientific and qualification work is devoted to the development of methods, algorithms and programs for detecting and correcting errors in the transmission of data over communication channels to ensure the integrity and reliability of the transmitted commands and data between computing devices, as well as when reading data from memory devices

Ichthyosen : Pathophysiologische Modelle der epidermalen Differenzierung [The ichthyoses : Pathophysiological models of epidermal differentiation].

The ichthyoses are a heterogeneous group of monogenetically inherited disorders of cornification, and characterized clinically by scaling or hyperkeratosis. Historically, they were classified by clinical features and inheritance patterns. As a result of the recent molecular biological revolution, the ichthyoses are now recognized as comprising many diverse entities. Importantly, identical phenotypes may be caused by mutations in multiple genes, while mutations in a single gene may result in multiple and sometimes widely divergent phenotypes. The considerable complexity of this clinically and genetically heterogeneous group of disorders has prompted the need for a new classification. A classification that uses terminology based on a combination of the clinical and molecular genetic details, for instance loricrin keratoderma, is desirable. In this chapter we will use in principle the nosology adopted recently by an international group of experts at the First Ichthyosis Consensus Conference in Sorèz, France

Integrating tobacco treatment into oncology care: Reach and effectiveness of evidence-based tobacco treatment across National Cancer Institute-designated cancer centers

PURPOSE: Quitting smoking improves patients\u27 clinical outcomes, yet smoking is not commonly addressed as part of cancer care. The Cancer Center Cessation Initiative (C3I) supports National Cancer Institute-designated cancer centers to integrate tobacco treatment programs (TTPs) into routine cancer care. C3I centers vary in size, implementation strategies used, and treatment approaches. We examined associations of these contextual factors with treatment reach and smoking cessation effectiveness. METHODS: This cross-sectional study used survey data from 28 C3I centers that reported tobacco treatment data during the first 6 months of 2021. Primary outcomes of interest were treatment reach (reach)-the proportion of patients identified as currently smoking who received at least one evidence-based tobacco treatment component (eg, counseling and pharmacotherapy)-and smoking cessation effectiveness (effectiveness)-the proportion of patients reporting 7-day point prevalence abstinence at 6-month follow-up. Center-level differences in reach and effectiveness were examined by center characteristics, implementation strategies, and tobacco treatment components. RESULTS: Of the total 692,662 unique patients seen, 44,437 reported current smoking. Across centers, a median of 96% of patients were screened for tobacco use, median smoking prevalence was 7.4%, median reach was 15.4%, and median effectiveness was 18.4%. Center-level characteristics associated with higher reach included higher smoking prevalence, use of center-wide TTP, and lower patient-to-tobacco treatment specialist ratio. Higher effectiveness was observed at centers that served a larger overall population and population of patients who smoke, reported a higher smoking prevalence, and/or offered electronic health record referrals via a closed-loop system. CONCLUSION: Whole-center TTP implementation among inpatients and outpatients, and increasing staff-to-patient ratios may improve TTP reach. Designating personnel with tobacco treatment expertise and resources to increase tobacco treatment dose or intensity may improve smoking cessation effectiveness

Ab initio simulations of liquid systems: Concentration dependence of the electric conductivity of NaSn alloys

Liquid NaSn alloys in five different compositions (20, 40, 50, 57 and 80% sodium) are studied using density functional calculations combined with molecular dynamics(Car-Parrinello method). The frequency-dependent electric conductivities for the systems are calculated by means of the Kubo-Greenwood formula. The extrapolated DC conductivities are in good agreement with the experimental data and reproduce the strong variation with the concentration. The maximum of conductivity is obtained, in agreement with experiment, near the equimolar composition. The strong variation of conductivity, ranging from almost semiconducting up to metallic behaviour, can be understood by an analysis of the densities-of-states.Comment: LaTex 6 pages and 2 figures, to appear in J.Phys. Cond. Ma

Dynamics of modal power distribution in a multimode semiconductor laser with optical feedback

The dynamics of power distribution between longitudinal modes of a multimode semiconductor laser subjected to external optical feedback is experimentally analyzed in the low-frequency fluctuation regime. Power dropouts in the total light intensity are invariably accompanied by sudden activations of several longitudinal modes. These activations are seen not to be simultaneous to the dropouts, but to occur after them. The phenomenon is statistically analysed in a systematic way, and the corresponding delay is estimated.Comment: 3 pages, 4 figures, revte

Surrogate regression modelling for fast seismogram generation and detection of microseismic events in heterogeneous velocity models

This is the author accepted manuscript. The final version is available from Oxford University Press (OUP) via the DOI in this record.Given a 3D heterogeneous velocity model with a few million voxels, fast generation of accurate seismic responses at specified receiver positions from known microseismic event locations is a well-known challenge in geophysics, since it typically involves numerical solution of the computationally expensive elastic wave equation. Thousands of such forward simulations are often a routine requirement for parameter estimation of microseimsic events via a suitable source inversion process. Parameter estimation based on forward modelling is often advantageous over a direct regression-based inversion approach when there are unknown number of parameters to be estimated and the seismic data has complicated noise characteristics which may not always allow a stable and unique solution in a direct inversion process. In this paper, starting from Graphics Processing Unit (GPU) based synthetic simulations of a few thousand forward seismic shots due to microseismic events via pseudo-spectral solution of elastic wave equation, we develop a step-by-step process to generate a surrogate regression modelling framework, using machine learning techniques that can produce accurate seismograms at specified receiver locations. The trained surrogate models can then be used as a high-speed meta-model/emulator or proxy for the original full elastic wave propagator to generate seismic responses for other microseismic event locations also. The accuracies of the surrogate models have been evaluated using two independent sets of training and testing Latin hypercube (LH) quasi-random samples, drawn from a heterogeneous marine velocity model. The predicted seismograms have been used thereafter to calculate batch likelihood functions, with specified noise characteristics. Finally, the trained models on 23 receivers placed at the sea-bed in a marine velocity model are used to determine the maximum likelihood estimate (MLE) of the event locations which can in future be used in a Bayesian analysis for microseismic event detection.This work has been supported by the Shell Projects and Technology. The Wilkes high performance GPU computing service at the University of Cambridge has been used in this work