575 research outputs found

    Deterministic multi-zone ice accretion modeling

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    The focus here is on a deterministic model of the surface roughness transition behavior of glaze ice. The initial smooth/rough transition location, bead formation, and the propagation of the transition location are analyzed. Based on the hypothesis that the smooth/rough transition location coincides with the laminar/turbulent boundary layer transition location, a multizone model is implemented in the LEWICE code. In order to verify the effectiveness of the model, ice accretion predictions for simple cylinders calculated by the multizone LEWICE are compared to experimental ice shapes. The glaze ice shapes are found to be sensitive to the laminar surface roughness and bead thickness parameters controlling the transition location, while the ice shapes are found to be insensitive to the turbulent surface roughness

    Progressive hearing loss in mice carrying a mutation in Usp53

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    UNLABELLED: Disordered protein ubiquitination has been linked to neurodegenerative disease, yet its role in inner ear homeostasis and hearing loss is essentially unknown. Here we show that progressive hearing loss in the ethylnitrosourea-generated mambo mouse line is caused by a mutation in Usp53, a member of the deubiquitinating enzyme family. USP53 contains a catalytically inactive ubiquitin-specific protease domain and is expressed in cochlear hair cells and a subset of supporting cells. Although hair cell differentiation is unaffected in mambo mice, outer hair cells degenerate rapidly after the first postnatal week. USP53 colocalizes and interacts with the tight junction scaffolding proteins TJP1 and TJP2 in polarized epithelial cells, suggesting that USP53 is part of the tight junction complex. The barrier properties of tight junctions of the stria vascularis appeared intact in a biotin tracer assay, but the endocochlear potential is reduced in adult mambo mice. Hair cell degeneration in mambo mice precedes endocochlear potential decline and is rescued in cochlear organotypic cultures in low potassium milieu, indicating that hair cell loss is triggered by extracellular factors. Remarkably, heterozygous mambo mice show increased susceptibility to noise injury at high frequencies. We conclude that USP53 is a novel tight junction-associated protein that is essential for the survival of auditory hair cells and normal hearing in mice, possibly by modulating the barrier properties and mechanical stability of tight junctions. SIGNIFICANCE STATEMENT: Hereditary hearing loss is extremely prevalent in the human population, but many genes linked to hearing loss remain to be discovered. Forward genetics screens in mice have facilitated the identification of genes involved in sensory perception and provided valuable animal models for hearing loss in humans. This involves introducing random mutations in mice, screening the mice for hearing defects, and mapping the causative mutation. Here, we have identified a mutation in the Usp53 gene that causes progressive hearing loss in the mambo mouse line. We demonstrate that USP53 is a catalytically inactive deubiquitinating enzyme and a novel component of tight junctions that is necessary for sensory hair cell survival and inner ear homeostasis

    The HIFI spectral survey of AFGL 2591 (CHESS). II. Summary of the survey

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    This paper presents the richness of submillimeter spectral features in the high-mass star forming region AFGL 2591. As part of the CHESS (Chemical Herschel Survey of Star Forming Regions) Key Programme, AFGL 2591 was observed by the Herschel/HIFI instrument. The spectral survey covered a frequency range from 480 up to 1240 GHz as well as single lines from 1267 to 1901 GHz (i.e. CO, HCl, NH3, OH and [CII]). Rotational and population diagram methods were used to calculate column densities, excitation temperatures and the emission extents of the observed molecules associated with AFGL 2591. The analysis was supplemented with several lines from ground-based JCMT spectra. From the HIFI spectral survey analysis a total of 32 species were identified (including isotopologues). In spite of the fact that lines are mostly quite week, 268 emission and 16 absorption lines were found (excluding blends). Molecular column densities range from 6e11 to 1e19 cm-2 and excitation temperatures range from 19 to 175 K. One can distinguish cold (e.g. HCN, H2S, NH3 with temperatures below 70 K) and warm species (e.g. CH3OH, SO2) in the protostellar envelope.Comment: Accepted to A&

    Analysis of the intensity of immune cell infiltration and immunoreactivity of RCAS1 in diffuse large B-cell lymphoma of the palatine tonsil and its microenvironment

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    Non-Hodgkin lymphoma of Waldeyer’s ring constitutes a small percentage of cases of palatine tonsil malignancies and its precise etiology remains unknown. RCAS1 (receptor cancer-binding antigen expressed on SiSo cells) has been demonstrated to be associated with poor prognosis, the development of lymph node metastases and participation in tumor microenvironment remodeling. Our aim is to analyze the potential role of RCAS1 expression in the tumor and tumor microenvironment in the development of early-stage palatine tonsil B-cell lymphomas. We selected 20 patients and analyzed tissue samples from the lymphoma and tumor microenvironment of each patient and from a reference group of 20 patients with chronic tonsillitis. The presence of RCAS1 protein immunoreactivity was demonstrated in 65 % of the examined tissue samples of diffuse large B-cell lymphoma and in 25 % of the analyzed stromata in which it was exhibited by CD68-positive cells identified as macrophages and dispersed throughout the stroma. RCAS1 immunoreactivity in the lymphoma tissue samples remained at a level comparable with that of the reference and was significantly higher in these samples than in those from the stroma. Chronic inflammation of the palatine tonsils thus results in intensive infiltration by various types of immune system cells and in excessive RCAS1 immunoreactivity, both of which confirm the important regulatory role of RCAS1 in the immune response in the mucosa-associated lymphatic tissue of Waldeyer’s ring. RCAS1 seems to be involved in creating tumor-induced inflammation in the tumor and its microenvironment

    Molecular Mechanisms Leading from Periodontal Disease to Cancer

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    Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigating tumorigenesis. We also present evidence for potential links between the RANKL–RANK signaling axis as well as circulating cytokines/leukocytes and carcinogenesis. Due to the nonconclusive data associating periodontitis and cancer reported in the case and cohort studies, we examine clinical trials relevant to the topic and summarize their outcome

    Phenotype and genotype associations of lung carcinoma with atypical adenomatoid hyperplasia, squamous cell dysplasia, and chromosome alterations in non-neoplastic bronchial mucosa

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    Abstract The frequency of preneoplastic lesions of the lung and bronchial mucosa as well as potential genotype alterations in spatial relationship to pulmonary malignancies still need intensive investigations in order to understand the occurrence and manifestation of lung cancer in detail. To investigate the contemporary manifestation of lung cancer precursor lesions, peripheral (non-neoplastic) lung parenchyma and bronchial mucosa of operated lung carcinomas were analyzed at distinct distances (1, 2, 3, and 4 cm) from the tumor boundary for pre-neoplastic lesions -atypical adenomatoid hyperplasia (AAH) and squamous cell dysplasia (SCD), in 150 surgical specimens. Short-term tissue cultures of additional 55 primary and secondary lung tumors and their surrounding non-neoplastic bronchial mucosa were performed at the same distances in order to search for chromosome alterations, i.e. genotype aberrations. In phenotype observations, atypical adenomatoid hyperplasia was noted in 19/150 (13%) cases, and squamous cell dysplasia in 46/150 (31%) cases. The degree of cellular atypia decreased with increasing distance from the tumor boundary in both AAH and SCM. AAH was observed more frequently in adenocarcinomas, SCQ more frequently in squamous cell carcinomas. In genotype observations, the average number of abnormal metaphases measured 4.5/10 high power fields (HPF) in primary lung carcinomas, and only 2/10 in metastases. Data indicate that the so-called preneoplastic lesions in the lung are not completely tumor-precursor lesions, but, in addition, induced by the tumor itself

    Occupational Risks during a Monkeypox Outbreak, Wisconsin, 2003

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    Veterinary staff were at high risk; standard veterinary infection-control guidelines should be followed
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