Factors contributing to the bacteriolytic effect of species of myxococci upon viable eubacteria

RESP-261

Endothelial Cell Contributions to COVID-19

Understanding of the clinical, histological and molecular features of the novel coronavirus 2019 (Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)) has remained elusive. Coronavirus disease 2019 (COVID-19) caused by this virus has unusual clinical presentation with regard to other related coronaviruses. Recent reports suggest that SARS-CoV-2, unlike other related viruses, infects and replicates within endothelial cells, which may explain a significant portion of the observed clinical pathology. Likewise, mounting evidence associates vascular and endothelial cell dysfunction with increased mortality. This review focuses on understanding how endothelial cell pathology is caused by SARS-CoV-2 at the molecular and cellular levels and how these events relate to COVID-19. A detailed examination of current knowledge regarding canonical inflammatory reaction pathways as well as alteration of endothelial cell-derived exosomes and transdifferentiation by SARS-CoV-2 is included in this assessment. Additionally, given an understanding of endothelial contributions to COVID-19, potential therapeutic aims are discussed, particularly as would affect endothelial function and pathology

Clinical Trials in Alzheimer’s Disease: A Hurdle in the Path of Remedy

Human clinical trials seek to ameliorate the disease states and symptomatic progression of illnesses that, as of yet, are largely untreatable according to clinical standards. Ideally, clinical trials test “disease-modifying drugs,” i.e., therapeutic agents that specifically modify pathological features or molecular bases of the disease and would presumably have a large impact on disease progression. In the case of Alzheimer’s disease (AD), however, this approach appears to have stalled progress in the successful development of clinically useful therapies. For the last 25 years, clinical trials involving AD have centered on beta-amyloid (Aβ) and the Aβ hypothesis of AD progression and pathology. According to this hypothesis, the progression of AD begins following an accumulation of Aβ peptide, leading to eventual synapse loss and neuronal cell death: the true overriding pathological feature of AD. Clinical trials arising from the Aβ hypothesis target causal steps in the pathway in order to reduce the formation of Aβ or enhance clearance, and though agents have been successful in this aim, they remain unsuccessful in rescuing cognitive function or slowing cognitive decline. As such, further use of resources in the development of treatment options for AD that target Aβ, its precursors, or its products should be reevaluated. The purpose of this review was to give an overview of how human clinical trials are conducted in the USA and to assess the results of recent failed trials involving AD, the majority of which were based on the Aβ hypothesis. Based on these current findings, it is suggested that lowering Aβ is an unproven strategy, and it may be time to refocus on other targets for the treatment of this disease including pathological forms of tau

A non-symmetric Yang-Baxter Algebra for the Quantum Nonlinear Schr\"odinger Model

We study certain non-symmetric wavefunctions associated to the quantum nonlinear Schr\"odinger model, introduced by Komori and Hikami using Gutkin's propagation operator, which involves representations of the degenerate affine Hecke algebra. We highlight how these functions can be generated using a vertex-type operator formalism similar to the recursion defining the symmetric (Bethe) wavefunction in the quantum inverse scattering method. Furthermore, some of the commutation relations encoded in the Yang-Baxter equation for the relevant monodromy matrix are generalized to the non-symmetric case.Comment: 31 pages; added some references; minor corrections throughou

Living and Dying at the Portus Romae

This paper presents the first results of research into plant, animal, and human remains from Portus, the maritime port of Imperial Rome, in order to examine the diet and geographical origins of its inhabitants between the second and sixth century AD. Comparisons with evidence from the excavation and ceramic analysis show clear changes throughout the period, with shifts in diet and patterns of foods import that can be related to the commercial and political changes following the breakdown of Roman of the Mediterranean

Collagen α1(XI) in Normal and Malignant Breast Tissue

Little is known about collagen XI expression in normal and malignant breast tissue. Tissue microarrays, constructed from 72 patients with breast carcinoma and matched normal tissue, were immunohistochemically stained with five antisera against isoform-specific regions of collagen α1(XI) N-terminal domain. Staining intensity was graded on a 0–3 scale in epithelial cytoplasm, stroma, and endothelial staining of the vasculature of each tissue core. The staining was compared to known pathologic parameters: age, tumor size, overall tumor grade, nuclear grade, tubule formation, mitotic counts, angiolymphatic invasion, node status, estrogen receptor status, progesterone receptor status, and HER-2/neu status. Estrogen and progesterone receptor status were used as a control for comparison. With antisera V1a and amino propeptide (Npp), stroma surrounding cancerous cells was found to have decreased collagen α1(XI) staining compared to stroma adjacent to normal epithelium (P=0.0006, P\u3c 0.0001). Collagen α1(XI) staining with V1a antiserum in cytoplasm of cancer cells demonstrated decreased intensity in metastasized primary tumors when compared to nonmetastasized primary tumors (P=0.009). Cytoplasmic staining with Npp antiserum in cancer demonstrated an inverse relationship to positive estrogen receptor status in cancer (P=0.012) and to progesterone receptor status (P=0.044). Stromal staining for Npp in cancerous tissue demonstrated an inverse relationship with tubule formation score (P=0.015). This is the first study to localize collagen XI within normal and malignant breast tissue. Collagen α1(XI) appears to be downregulated in stroma surrounding breast cancer. Detection of collagen XI in breast tissue may help predict women who have lymph node metastases

Designing and Piloting a Tool for the Measurement of the Use of Pronunciation Learning Strategies

What appears to be indispensable to drive the field forward and ensure that research findings will be comparable across studies and provide a sound basis for feasible pedagogic proposals is to draw up a classification of PLS and design on that basis a valid and reliable data collection tool which could be employed to measure the use of these strategies in different groups of learners, correlate it with individual and contextual variables, and appraise the effects of training programs. In accordance with this rationale, the present paper represents an attempt to propose a tentative categorization of pronunciation learning strategies, adopting as a point of reference the existing taxonomies of strategic devices (i.e. O'Malley and Chamot 1990; Oxford 1990) and the instructional options teachers have at their disposal when dealing with elements of this language subsystem (e.g. Kelly 2000; Goodwin 2001). It also introduces a research instrument designed on the basis of the classification that shares a number of characteristics with Oxford's (1990) Strategy Inventory for Language Learning but, in contrast to it, includes both Likert-scale and open-ended items. The findings of a pilot study which involved 80 English Department students demonstrate that although the tool requires considerable refinement, it provides a useful point of departure for future research into PLS

Data Management Tools to Measure the Impact of Core Facilities

The Biomolecular Research Center at Boise State University is a research core facility that supports the study of biomolecules with an emphasis on protein structure and function, molecular interactions, and imaging. The mission of the core is to facilitate access to instrumentation that might otherwise be unavailable because of the cost, training for new users, and scientific staff with specialized skills to support early-stage investigators, as well as more established senior investigators. Data collection and management of users and their research output is essential to understand the impact of the center on the research environment and research productivity. However, challenges are often encountered when trying to fully quantify the impact of a core facility on the institution, as well as on the career success of individual investigators. This challenge can be exacerbated under the conditions of unprecedented growth in biomedical research and shared core facility use that has been experienced at Boise State University, an institution of emerging research excellence. Responding to these challenges required new approaches to information management, reporting, assessment, and evaluation. Our specific data management, evaluation, and assessment challenges included 1) collection and management of annual reporting information from investigators, staff, and students in a streamlined manner that did not lead to reporting fatigue; 2) application of software for analyzing synergy among programs’ management strategy and investigator success; and 3) consolidation of core facility management, billing, and reporting capabilities into 1 cohesive system. The data management tools adopted had a beneficial effect by saving time, reducing administrative burden, and streamlining reporting. Practices implemented for data management have facilitated effective evaluation and future program planning. The substantial burden of assessment requirements necessitates early consideration of a strategy for data management to allow assessment of impact

Oncostatin M Binds to Extracellular Matrix in a Bioactive Conformation: Implications for Inflammation and Metastasis

Oncostatin M (OSM) is an interleukin-6-like inflammatory cytokine reported to play a role in a number of pathological processes including cancer. Full-length OSM is expressed as a 26 kDa protein that can be proteolytically processed into 24 kDa and 22 kDa forms via removal of C-terminal peptides. In this study, we examined both the ability of OSM to bind to the extracellular matrix (ECM) and the activity of immobilized OSM on human breast carcinoma cells. OSM was observed to bind to ECM proteins collagen types I and XI, laminin, and fibronectin in a pH-dependent fashion, suggesting a role for electrostatic bonds that involves charged amino acids of both the ECM and OSM. The C-terminal extensions of 24 kDa and 26 kDa OSM, which contains six and thirteen basic amino acids, respectively, enhanced electrostatic binding to ECM at pH 6.5–7.5 when compared to 22 kDa OSM. The highest levels of OSM binding to ECM, though, were observed at acidic pH 5.5, where all forms of OSM bound to ECM proteins to a similar extent. This indicates additional electrostatic binding properties independent of the OSM C-terminal extensions. The reducing agent dithiothreitol also inhibited the binding of OSM to ECM suggesting a role for disulfide bonds in OSM immobilization. OSM immobilized to ECM was protected from cleavage by tumor-associated proteases and maintained activity following incubation at acidic pH for extended periods of time. Importantly, immobilized OSM remained biologically active and was able to induce and sustain the phosphorylation of STAT3 in T47D and ZR-75-1 human breast cancer cells over prolonged periods, as well as increase levels of STAT1 and STAT3 protein expression. Immobilized OSM also induced epithelial–mesenchymal transition-associated morphological changes in T47D cells. Taken together, these data indicate that OSM binds to ECM in a bioactive state that may have important implications for the development of chronic inflammation and tumor metastasis

Advanced Scanning Electron Microscopy Methods and Applications to Integrated Circuit Failure Analysis

Semiconductor device failure analysis using the scanning electron microscope (SEM) has become a standard component of integrated circuit fabrication. Improvements in SEM capabilities and in digital imaging and processing have advanced standard acquisition modes and have promoted new failure analysis methods. The physical basis of various data acquisition modes, both standard and new, and their implementation on a computer controlled SEM image acquisition/processing system are discussed, emphasizing the advantages of each method. Design considerations for an integrated, online failure analysis system are also described. Recent developments in the integration of the information provided by electron beam analysis, conventional integrated circuit (IC) testing, computer-aided design (CAD), and device parameter testing into a single system promise to provide powerful future tools for failure analysis