A long-term "memory" of HIF induction in response to chronic mild decreased oxygen after oxygen normalization

Background Endothelial dysfunction (ED) is functionally characterized by decreased vasorelaxation, increased thrombosis, increased inflammation, and altered angiogenic potential, has been intimately associated with the progression and severity of cardiovascular disease. Patients with compromised cardiac function oftentimes have a state of chronic mild decreased oxygen at the level of the vasculature and organs, which has been shown to exacerbate ED. Hypoxia inducible factor (HIF) is a transcription factor complex shown to be the master regulator of the cellular response to decreased oxygen levels and many HIF target genes have been shown to be associated with ED. Methods Human endothelial and aortic smooth muscle cells were exposed either to A) normoxia (21% O2) for three weeks, or to B) mild decreased oxygen (15% O2) for three weeks to mimic blood oxygen levels in patients with heart failure, or to C) mild decreased oxygen for two weeks followed by one week of normoxia ("memory" treatment). Levels of HIF signaling genes (HIF-1α, HIF-2α, VEGF, BNIP3, GLUT-1, PAI-1 and iNOS) were measured both at the protein and mRNA levels. Results It was found that chronic exposure to mild decreased oxygen resulted in significantly increased HIF signaling. There was also a "memory" of HIF-1α and HIF target gene induction when oxygen levels were normalized for one week, and this "memory" could be interrupted by adding a small molecule HIF inhibitor to the last week of normalized oxygen. Finally, levels of ubiquitylated HIF-1α were reduced in response to chronic mild decreased oxygen and were not full restored after oxygen normalization. Conclusion These data suggest that HIF signaling may be contributing to the pathogenesis of endothelial dysfunction and that normalization of oxygen levels may not be enough to reduce vascular stress

Comparing methods for estimating Manning's roughness coefficient on a portion of the South Fork of Chester Creek

This report compares several different methods used for estimating the Manning roughness coefficient of a reach using observed conditions during spring runoff. A survey was taken of the South Fork of Chester Creek in the small valley between the Engineering and Computation Building and the North-West Parking Lot at UAA. The survey included 16 cross sections, a center line profile, water surface elevations (WSE’s), and flow velocity readings at each cross section. Based on observed conditions, a model was created in HEC-RAS to calculate the hydraulic characteristics at each cross section. These hydraulic characteristics, along with downstream cross section lengths and head losses, were used to calculate the composite roughness of the reach. This value was then compared to a visual method that accounts for flow-retarding factors, and an empirical method developed in a laboratory. The roughness values computed for the analytical, empirical, and visual methods were 0.071, 0.045, and 0.077 respectively. Additionally, the three computed coefficients were compared with two methods that involve matching table values. The two approximate table values were 0.11 and 0.10. Supplementary methods not used in the analysis are also discussed.Table of Figures / List of Tables / Table of Equations / Abstract / 1.0 Introduction / 2.0 Literature Review / 3.0 Methodology / 4.0 Results / 5.0 Conclusions / 6.0 Recommendations / 7.0 References / 8.0 Appendi

Analysis of MUM1/IRF4 Protein Expression Using Tissue Microarrays and Immunohistochemistry

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З історії озброєння козацького війська першої половини 18 ст.

В низці реформ, які спіткали у 18 ст. військо гетьманського регіменту, та їхня невелика частина, котра стосувалася озброєння є чи не найменше відомою не тільки широкому загалу істориків, але й вузьким спеціалістам з періоду. Перші спроби прищеплення козакам “регулярства” ще з часів Петра І були спрямовані головним чином, на впровадження адміністративних і організаційних новацій, впорядкування фінансування й забезпечення при одночасному нехтуванні власне озброєнням і бойовою підготовкою війська. Втім, саме вони після Північної війни і “Низових” походів, які виявили всі недоліки, притаманні становій організації збройних сил, дуже гостро поставили питання боєздатності козацьких полків. Наріжною проблемою була якість озброєння реєстрових козаків. Як відомо, для цієї частини гетьманського війська традиційно не існувало жодних регламентацій, що б визначали види й перелік озброєння, термін його служби, навчання застосування тощо. Виняток становили лише наймані формування, забезпечення яких вогнепальною й деякими іншими видами зброї, а також боєприпасами, перебрала на себе держава [1]. На початку 18 ст. комплекс озброєння лівобережного козацтва загалом мало чим відрізнявся від попереднього століття, складаючись з традиційних піки, шаблі, різноманітних видів рушниць й іноді – пістолів і луків зі стрілами [2]. Кожен козак мусив власним коштом купувати необхідну йому амуніцію та зброю, вряди-годи дістаючи зі скарбу лише боєприпаси до неї. В умовах постійно прогресуючої майнової диференціації козацтва це призводило з одного боку до того, що частина збіднілого товариства взагалі не могла відбувати воєнну службу, а та, що була спроможною оплачувати спорядження, озброювалася відповідно не до воєнних потреб, а своїх матеріальних можливостей і бажання. Так, при підготовці кампанії 1707 р., Петро І наказував Мазепі виправити до діючої армії виборних козаків і компанійців, “которые б имели добрые кони и ружье”, дорікаючи за минулорічні бої в яких у козаків “почитай что ни у кого сабли не видали, кроме пищалей и сайдаков” [3]. Стан озброєності істотно погіршився ще й внаслідок поразок гетьманського війська у битвах зі шведами, виснажливих чергувань на форпостах і походів на Каспій. Годі й говорити, що за таких умов будь-яка уніфікація козацького озброєння була справою бажаною, але надзвичайно складною. Скарб Гетьманщини після численних реформ Малоросійської колегії й хронічної децентралізованості фінансового господарства навряд чи зміг би подужати проведення подібних заходів. Окрім того, в Україні практично не існувало ані необхідної сировинної бази, ані мережі зброярських підприємств мануфактурного типу, котрі б працювали на державне замовлення й могли б виконувати великі замовлення. Розвиток численних рудень Лівобережжя, котрі були зобовязані віддавати частину продукованого ними заліза на потребу війська, як відомо, не призвів до їх перетворення на металургійні заводи

Going Beyond Promoting: Preparing Students to Creatively Solve Future Problems

While we cannot know what problems the future will bring, we can be almost certain that solving them will require creativity. In this article we describe how our course, a first-year undergraduate mathematics course, supports creative problem solving. Creative problem solving cannot be learned through a single experience, so we provide our students with a blend of experiences. We discuss how the course structure enables creative problem solving through class instruction, during class activities, during out of class assessments, and during in class assessments. We believe this course structure increases student comfort with solving open-ended and ill-defined problems similar to what they will encounter in the real world

A five-year observance of changes in the cardiovascular risk profile in 505 HIV-positive individuals

Purpose: Since the introduction of antiretroviral therapy (ART) and the extension of life expectancy, HIV-infected persons have shown an increasing number of cardiovascular events. The reduction of cardiovascular risk factors becomes a new challenge in HIV care. One of the main objectives of the HIV&HEART study is to examine the development of cardiovascular risk factors and treatment of cardiovascular diseases. Methods: This study is an on-going, prospective, regional multicentre trial that was conducted to analyse the frequency and clinical course of cardiac disorders as well as cardiovascular risk factors in HIV-infected patients. 505 HIV-infected outpatients were recruited at baseline (BL) and re-examined during 5-year follow up (5YFU). Results: 84% of 505 eligible HIV-infected patients were male. The average age was 44.3±9.5 years at BL. The proportion of ART-treated patients increased from 85.7% at BL to 96.4% at 5YFU. During the 5-year observation period mean cardiovascular risk detected by Framingham score increased from 6% at BL to 10% at 5YFU. Even after adjusting for age there was a difference in the Framingham score of 2%. Between BL and 5YFU systolic blood pressure increased from 128.4±19.8 mmHg to 138.3±19.9 mmHg in spite of an intensified use of antihypertensive drugs, from 11.9% at BL to 24.0% at 5YFU. The rate of participants with adiposity, characterised by a BMI>30, increased from 7.9% at BL to 11.2% at 5YFU. Lipid-lowering therapy was applied in 10.3% of the patients at BL and in 13.9% at 5YFU. Triglycerides (TAG)≥200 mg/dl reduced from 38.9% at BL to 36.8% at 5YFU; in contrast cholesterol values≥200 mg/dl elevated from 57.8% to 61.8%. The same trend was observed in HDL≤40 mg/dl. Here we found a change from 29.2% versus 31.3%. Doing regular sports elevated from 1.9% to 3.3%. The count of smokers increased for 2.8% and also mean pack-years changes from 24 to 26.5 pack-years. Conclusion: During a 5-year period the cardiovascular risk in Framingham score increased disproportionately high in this HIV-infected cohort even after adjusting for age. There was an increasing blood pressure although an elevated use of antihypertensive therapy. There was also a tendency of elevating BMI and an increasing trend in smoking behavior. As protective facts, we found a tendency in doing sports and a decreasing TAG value during intensifying lipid-lowering therapy. Cardiovascular risk was increasing, in spite of interventions

Expert Opinion on Benefits of Long-Chain Omega-3 Fatty Acids (DHA and EPA) in Aging and Clinical Nutrition

Life expectancy is increasing and so is the prevalence of age-related non-communicable diseases (NCDs). Consequently, older people and patients present with multi-morbidities and more complex needs, putting significant pressure on healthcare systems. Effective nutrition interventions could be an important tool to address patient needs, improve clinical outcomes and reduce healthcare costs. Inflammation plays a central role in NCDs, so targeting it is relevant to disease prevention and treatment. The long-chain omega-3 polyunsaturated fatty acids (omega-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are known to reduce inflammation and promote its resolution, suggesting a beneficial role in various therapeutic areas. An expert group reviewed the data on omega-3 LCPUFAs in specific patient populations and medical conditions. Evidence for benefits in cognitive health, age- and disease-related decline in muscle mass, cancer treatment, surgical patients and critical illness was identified. Use of DHA and EPA in some conditions is already included in some relevant guidelines. However, it is important to note that data on the effects of omega-3 LCPUFAs are still inconsistent in many areas (e.g., cognitive decline) due to a range of factors that vary amongst the trials performed to date; these factors include dose, timing and duration; baseline omega-3 LCPUFA status; and intake of other nutrients. Well-designed intervention studies are required to optimize the effects of DHA and EPA in specific patient populations and to develop more personalized strategies for their use.<br/

Identification of Quantitative Trait Loci for Flowering Time in a Field-Grown \u3cem\u3eLolium Perene x Lolium Multiflorum\u3c/em\u3e Mapping Population

Perennial ryegrass (L. perenne) and annual, or Italian, ryegrass (L. multiflorum) are considered to be separate species by the seed trade, and are used and bred for distinct purposes. However, the two species are cross-fertile. Seed producers rely on the different flowering times of the two species to produce pure seed. Flowering times can overlap, leading to genetic mixing. Contamination of perennial ryegrass seed lots with annual types is an expensive problem for grass seed producers in western Oregon, USA

Co-expression of CD56 and CD30 in lymphomas with primary presentation in the skin: clinicopathologic, immunohistochemical and molecular analyses of seven cases

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74772/1/j.1600-0560.2000.027008392.x.pd

Acute Disseminated Encephalomyelitis with Seizures and Myocarditis: A Fatal Triad.

Autoimmune pathology of acute disseminated encephalomyelitis (ADEM) is generally restricted to the brain. Our objective is to expand the phenotype of ADEM. A four-year-old girl was admitted to the pediatric emergency room of a university medical center five days after a common upper respiratory tract infection. Acute symptoms were fever, leg pain, and headaches. She developed meningeal signs, and her level of consciousness dropped rapidly. Epileptic seizure activity started, and she became comatose, requiring intubation and mechanical ventilation. Serial brain magnetic resonance imaging (MRI) illustrated the fulminant development of ADEM. Treatment escalation with high-dose corticosteroids, immunoglobulins, and plasma exchange did not lead to clinical improvement. On day ten, the patient developed treatment-refractory cardiogenic shock and passed away. The postmortem assessment confirmed ADEM and revealed acute lymphocytic myocarditis, likely explaining the acute cardiac failure. Human metapneumovirus and picornavirus were detected in the tracheal secrete by PCR. Data sources-medical chart of the patient. This case is consistent with evidence from experimental findings of an association of ADEM with myocarditis as a postinfectious systemic autoimmune response, with life-threatening involvement of the brain and heart