Thermal inactivation and conformational lock studies on glucose oxidase

In this study, the dissociative thermal inactivation and conformational lock theories are applied for the homodimeric enzyme glucose oxidase (GOD) in order to analyze its structure. For this purpose, the rate of activity reduction of glucose oxidase is studied at various temperatures using b-D-glucose as the substrate by incubation of enzyme at various temperatures in the wide range between 40 and 70 �C using UV–Vis spectrophotometry. It was observed that in the two ranges of temperatures, the enzyme has two different forms. In relatively low temperatures, the enzyme is in its dimeric state and has normal activity. In high temperatures, the activity almost disappears and it aggregates. The above achievements are confirmed by dynamic light scattering. The experimental parameter ‘‘n’’ as the obvious number of conformational locks at the dimer interface of glucose oxidase is obtained by kinetic data, and the value is near to two. To confirm the above results, the X-ray crystallography structure of the enzyme, GOD (pdb, 1gal), was also studied. The secondary and tertiary structures of the enzyme to track the thermal inactivation were studied by circular dichroism and fluorescence spectroscopy, respectively. We proposed a mechanism model for thermal inactivation of GOD based on the absence of the monomeric form of the enzyme by circular dichroism and fluorescence spectroscopy

Метод повышения надежности информационных телекоммуникационных облаков путем внедрения гомогенности

У статті розглянуто підхід до проектування інформаційної хмари шляхом впровадження гомогенності в функціональні вузли. Розглянуто метод, що дозволяє виключити з системи керуючі вузли, вихід з ладу яких, призводить до відмови всієї системи. Розглянуто питання застосування та впровадження систем, побудованих на базі гомогенного резервування. Був приведений кінцевий детермінований автомат, який описує переходи між станами вузла інформаційної хмари. Дано математичне підтвердження надійності даного методу проектування інформаційних хмар. Була виведена рекурсивна формула і умова виходу з рекурсії, що дозволяє ефективно обчислити надійність системи в залежності від кількості вузлів системи. Було доведено, що надійність системи зростає при збільшенні кількості вузлів за експоненціальним законом.The approach to the information cloud design through the introduction of homogeneity is presented in the article. The method that is excluding single points of failure is considered in the article. The usage examples and integration of the systems that were developed on the basis of homogeneous redundancy are introduced as well. It was given deterministic finite automaton, which describes the state transitions of the nodes in the cloud. Article also describes the mathematical proof of the method`s reliability. Recursive formula and the exit condition of the recursion were derived, which allow efficient computing of the reliability of the system that depends on the number of nodes. It has been proved that the reliability of the system increases with the number of nodes exponentially.В статье рассмотренный подход к проектированию информационного облака путем внедрения гомогенности в функциональные узлы. Рассмотрен метод, позволяющий исключить из системы управляющие узлы, выход из строя которых, приводит к отказу всей системы. Рассмотрен вопрос применения и внедрения систем, построенных на базе гомо-генного резервирования. Был приведен конечный детерминированный автомат, который описывает переходы между состояниями узла информационного облака. Дано математическое подтверждение надежности данного метода проектирования информационных облаков. Была выведена рекурсивная формула и условие выхода из рекурсии, позволяющая эффективно вычислить надежность системы в зависимости от количества узлов системы. Было доказано, что надежность системы растет при увеличении количества узлов по экспоненциальному закону

Randomized comparison of single dose of recombinant human IL-12 versus placebo for restoration of hematopoiesis and improved survival in rhesus monkeys exposed to lethal radiation

BACKGROUND: The hematopoietic syndrome of the acute radiation syndrome (HSARS) is a life-threatening condition in humans exposed to total body irradiation (TBI); no drugs are approved for treating this condition. Recombinant human interleukin-12 (rHuIL-12) is being developed for HSARS mitigation under the FDA Animal Rule, where efficacy is proven in an appropriate animal model and safety is demonstrated in humans. METHODS: In this blinded study, rhesus monkeys (9 animals/sex/dose group) were randomized to receive a single subcutaneous injection of placebo (group 1) or rHuIL-12 at doses of 50, 100, 250, or 500 ng/kg (groups 2–5, respectively), without antibiotics, fluids or blood transfusions, 24–25 hours after TBI (700 cGy). RESULTS: Survival rates at Day 60 were 11%, 33%, 39%, 39%, and 50% for groups 1–5, respectively (log rank p < 0.05 for each dose vs. control). rHuIL-12 also significantly reduced the incidences of severe neutropenia, severe thrombocytopenia, and sepsis (positive hemoculture). Additionally, bone marrow regeneration following TBI was significantly greater in monkeys treated with rHuIL-12 than in controls. CONCLUSIONS: Data from this study demonstrate that a single injection of rHuIL-12 delivered one day after TBI can significantly increase survival and reduce radiation-induced hematopoietic toxicity and infections. These data significantly advance development of rHuIL-12 toward approval under the Animal Rule as an effective stand-alone medical countermeasure against the lethal effects of radiation exposure

Anthropology, Brokerage and Collaboration in the development of a Tongan Public Psychiatry: Local Lessons for Global Mental Health

The Global Mental Health (GMH) movement has revitalised questions of the translatability of psychiatric concepts and the challenges of community engagement in countries where knowledge of the biomedical basis for psychiatric diagnosis is limited or challenged by local cultural codes. In Tonga, the local psychiatrist Dr Puloka has successfully established a publicly accessible psychiatry that has raised admission rates for serious mental illness and addressed some of the stigma attached to diagnosis. On the basis of historical analysis and ethnographic fieldwork with healers, doctors and patients since 1998, this article offers an ethnographic contextualization of the development and reception of three key interventions during the 1990s inspired by traditional healing and reliant on the translation of psychiatric terms and diagnosis. Dr Puloka’s use of medical anthropological and transcultural psychiatry research informed a community engaged brokerage between the implications of psychiatric nosologies and local needs. As such it reveals deficiencies in current polarised positions on the GMH project and offers suggestions to address current challenges of the Global Mental Health movement

The challenges of communicating research evidence in practice: perspectives from UK health visitors and practice nurses

&lt;p&gt;Background: Health practitioners play a pivotal role in providing patients with up-to-date evidence and health information. Evidence-based practice and patient-centred care are transforming the delivery of healthcare in the UK. Health practitioners are increasingly balancing the need to provide evidence-based information against that of facilitating patient choice, which may not always concur with the evidence base. There is limited research exploring how health practitioners working in the UK, and particularly those more autonomous practitioners such as health visitors and practice nurses working in community practice settings, negotiate this challenge. This research provides a descriptive account of how health visitors and practice nurses negotiate the challenges of communicating health information and research evidence in practice.&lt;/p&gt; &lt;p&gt;Methods: A total of eighteen in-depth telephone interviews were conducted in the UK between September 2008 and May 2009. The participants comprised nine health visitors and nine practice nurses, recruited via adverts on a nursing website, posters at a practitioner conference and through recommendation. Thematic analysis, with a focus on constant comparative method, was used to analyse the data.&lt;/p&gt; &lt;p&gt;Results: The data were grouped into three main themes: communicating evidence to the critically-minded patient; confidence in communicating evidence; and maintaining the integrity of the patient-practitioner relationship. These findings highlight some of the daily challenges that health visitors and practice nurses face with regard to the complex and dynamic nature of evidence and the changing attitudes and expectations of patients. The findings also highlight the tensions that exist between differing philosophies of evidence-based practice and patient-centred care, which can make communicating about evidence a daunting task.&lt;/p&gt; &lt;p&gt;Conclusions: If health practitioners are to be effective at communicating research evidence, we suggest that more research and resources need to be focused on contextual factors, such as how research evidence is negotiated, appraised and communicated within the dynamic patient-practitioner relationship.&lt;/p&gt

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

System taxonomy of financial security

The structure of the financial security of Ukraine and the legal basis of the state policy in the field of the financial security of Ukraine are analyzed. Based on systematized assumptions, on the basis of which the term “security” should be formed, the theoretical approach to the interpretation of the category “financial security of the country” has been improved, which is considered as the conditions for the functioning of the country's financial system, quantified by means of summarizing, fiscal, tax, debt security and security of the non-banking financial sector, in which the action of internal and external threats does not cause negative processes in this complex system and does not prevent the creation of favorable financial conditions for its sustainable developmen

Budgetary security of Ukraine: dynamics of level in the conditions of globalization changes

The article analyzes the secure state of the budgetary system in Ukraine in 2009-2018. The features of the structure of tax revenues to the state budget is found out, the dynamics of the GDP redistribution level through the consolidated budget is studied. The tendencies of change of the integral index of budgetary security are described. The paper investigates the peculiarities of the development of the budgetary system in Ukraine in the field of gender budgeting. Its purpose is to increase the efficiency of budget expenditures by taking into account the different needs of men and women, reducing the gender gap. The article emphasizes that the strategic imperative for strengthening the budgetary security of Ukraine is the reforming of the budgetary system taking into account the entrepreneurial initiative, economic pragmatism and social responsibility

A Reporter Screen in a Human Haploid Cell Line Identifies CYLD as a Constitutive Inhibitor of NF-κB

The development of forward genetic screens in human haploid cells has the potential to transform our understanding of the genetic basis of cellular processes unique to man. So far, this approach has been limited mostly to the identification of genes that mediate cell death in response to a lethal agent, likely due to the ease with which this phenotype can be observed. Here, we perform the first reporter screen in the near-haploid KBM7 cell line to identify constitutive inhibitors of NF-κB. CYLD was the only currently known negative regulator of NF-κB to be identified, thus uniquely distinguishing this gene. Also identified were three genes with no previous known connection to NF-κB. Our results demonstrate that reporter screens in haploid human cells can be applied to investigate the many complex signaling pathways that converge upon transcription factors

Alternative sources of funding for the development of united territorial communities

The article proves that it is important to strengthen financial capacity of united territorial communities through different financial and socio-economic mechanisms in the modern conditions of communities’ decentralization and further development. The article analyzes the current trends in financing the development of united territorial communities, reveals the benefits and opportunities for attracting alternative sources of funding. An algorithm for attracting grant funds for the development of UTC and other proposals that will increase the financial capacity of UTC in the long term and the implementation of local development initiatives are propose