45 research outputs found

    Web-based relay management with biometric authentication

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    This thesis proposes a web-based system for managing digital relay settings. These relays are deployed in the power system to protect sensitive and expensive equipment from physical damage during system faults and overload conditions. Providing this capability exposes these devices to the same cyber security threats that corporations have faced for many years.;This thesis investigates the risks and requirements for deploying the proposed system. A breakdown in the protection that these relays provide would cause power outages. The cost of outages can be significant. Therefore cyber security is critical in the system design. Cyber security requirements for the power industry identify access control as an important aspect for the protection of its infrastructure. If properly implemented, biometrics can be used to strengthen access control to computer systems.;The web-based relay management system uses fingerprint authentication along with a username and password to provide access control. Website users are given access to functionality based on user roles. Only high level users may attempt relay setting modification. The relay management system interacts with a database that stores the current relay settings, relay setting restrictions, and a queue of relay updates. A process is implemented to verify attempted setting changes against these setting restrictions. This provides an extra security layer if users attempt harmful changes to protection schemes. Valid setting changes are added to the queue and a separate relay update program communicates these changes to the relay. The database and relay update program protect the relays from direct modification. These features combined with biometric authentication provide a strong layered scheme for protecting relays, while supplying an easy to use interface for remotely using their capabilities

    Synaptic Defects in the Spinal and Neuromuscular Circuitry in a Mouse Model of Spinal Muscular Atrophy

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    Spinal muscular atrophy (SMA) is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7). In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs) in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3–5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1)-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy

    Assessing the Societal Impact of Research: The Relational Engagement Approach

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    Marketing and policy researchers aiming to increase the societal impact of their scholarship should engage directly with relevant stakeholders. For maximum societal effect, this engagement needs to occur both within the research process and throughout the complex process of knowledge transfer. The authors propose that a relational engagement approach to research impact complements and builds on traditional approaches. Traditional approaches to impact employ bibliometric measures and focus on the creation and use of journal articles by scholarly audiences, an important but incomplete part of the academic process. The authors recommend expanding the strategies and measures of impact to include process assessments for specific stakeholders across the entire course of impact, from the creation, awareness, and use of knowledge to societal impact. This relational engagement approach involves the cocreation of research with audiences beyond academia. The authors hope to begin a dialogue on the strategies researchers can use to increase the potential societal benefits of their research

    The Photosynthetic Apparatus and Its Regulation in the Aerobic Gammaproteobacterium Congregibacter litoralis gen. nov., sp. nov

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    BACKGROUND: There is accumulating evidence that in some marine environments aerobic bacteriochlorophyll a-producing bacteria represent a significant part of the microbial population. The interaction of photosynthesis and carbon metabolism in these interesting bacteria is still largely unknown and requires further investigation in order to estimate their contribution to the marine carbon cycle. METHODOLOGY/PRINCIPAL FINDINGS: Here, we analyzed the structure, composition and regulation of the photosynthetic apparatus in the obligately aerobic marine gammaproteobacterium KT71(T). Photoheterotrophically grown cells were characterized by a poorly developed lamellar intracytoplasmic membrane system, a type 1 light-harvesting antenna complex and a photosynthetic reaction center associated with a tetraheme cytochrome c. The only photosynthetic pigments produced were bacteriochlorophyll a and spirilloxanthin. Under semiaerobic conditions KT71(T) cells expressing a photosynthetic apparatus showed a light-dependent increase of growth yield in the range of 1.3-2.5 fold. The expression level of the photosynthetic apparatus depended largely on the utilized substrate, the intermediary carbon metabolism and oxygen tension. In addition, pigment synthesis was strongly influenced by light, with blue light exerting the most significant effect, implicating that proteins containing a BLUF domain may be involved in regulation of the photosynthetic apparatus. Several phenotypic traits in KT71(T) could be identified that correlated with the assumed redox state of growing cells and thus could be used to monitor the cellular redox state under various incubation conditions. CONCLUSIONS/SIGNIFICANCE: In a hypothetical model that explains the regulation of the photosynthetic apparatus in strain KT71(T) we propose that the expression of photosynthesis genes depends on the cellular redox state and is maximal under conditions that allow a balanced membrane redox state. So far, bacteria capable of an obligately aerobic, photosynthetic metabolism constitute a unique phenotype within the class Gammaproteobacteria, so that it is justified to propose a new genus and species, Congregibacter litoralis gen. nov, sp. nov., represented by the type strain KT71(T) ( = DSM 17192(T) = NBRC 104960(T))

    A Comparative Evaluation of Pulmonary Artery Balloon Counterpulsation and a Centrifugal Flow Pump in an Experimental Model of Right Ventricular Infarction

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    To compare the efficiency of pulmonary artery balloon counterpulsation and a centrifugal flow pump in reversing the hemodynamic consequences of acute right-sided heart failure, we employed both devices in 14 Yorkshire pigs in which right ventricular infarction was created via surgical ligation of branches of the right coronary artery. Pulmonary artery balloon counterpulsation improved some of the indicators of right heart failure, as manifested by significantly decreased right atrial pressure and increased mean systemic blood pressure. In contrast, the centrifugal flow pump consistently and significantly reversed all of the hemodynamic consequences of right ventricular infarction. In comparison to pulmonary artery balloon counterpulsation, the centrifugal flow pump resulted in lower right atrial pressures (p=0.020), lower mean pulmonary pressures (p<0.0001), increased left atrial pressures (p=0.026), increased cardiac output (p<0.0001), and increased mean systemic blood pressures (p<0.0001). Possible mechanisms to explain the superiority of the centrifugal flow pump include better hemodynamic unloading of the failing myocardium and independence from right ventricular output

    Global effects of agriculture on fluvial dissolved organic matter

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    Agricultural land covers approximately 40% of Earth's land surface and affects hydromorphological, biogeochemical and ecological characteristics of fluvial networks. In the northern temperate region, agriculture also strongly affects the amount and molecular composition of dissolved organic matter (DOM), which constitutes the main vector of carbon transport from soils to fluvial networks and to the sea and is involved in a large variety of biogeochemical processes. Here, we provide first evidence about the wider occurrence of agricultural impacts on the concentration and composition of fluvial DOM across climate zones of the northern and southern hemispheres. Both extensive and intensive farming altered fluvial DOM towards a more microbial and less plant-derived composition. Moreover, intensive farming significantly increased dissolved organic nitrogen (DON) concentrations. The DOM composition change and DON concentration increase differed among climate zones and could be related to the intensity of current and historical nitrogen fertilizer use. As a result of agriculture intensification, increased DON concentrations and a more microbial-like DOM composition likely will enhance the reactivity of catchment DOM emissions, thereby fuelling the biogeochemical processing in fluvial networks and resulting in higher ecosystem productivity and CO2 outgassing

    Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition.

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    BackgroundMalignant melanoma is an aggressive tumor type that often develops drug resistance to targeted therapeutics. The production of colony stimulating factor 1 (CSF-1) in tumors recruits myeloid cells such as M2-polarized macrophages and myeloid derived suppressor cells (MDSC), leading to an immune suppressive tumor milieu.MethodsWe used the syngeneic mouse model of BRAF (V600E) -driven melanoma SM1, which secretes CSF-1, to evaluate the ability of the CSF-1 receptor (CSF-1R) inhibitor PLX3397 to improve the antitumor efficacy of the oncogenic BRAF inhibitor vemurafenib.ResultsCombined BRAF and CSF-1R inhibition resulted in superior antitumor responses compared with either therapy alone. In mice receiving PLX3397 treatment, a dramatic reduction of tumor-infiltrating myeloid cells (TIM) was observed. In this model, we could not detect a direct effect of TIMs or pro-survival cytokines produced by TIMs that could confer resistance to PLX4032 (vemurafenib). However, the macrophage inhibitory effects of PLX3397 treatment in combination with the paradoxical activation of wild type BRAF-expressing immune cells mediated by PLX4032 resulted in more tumor-infiltrating lymphocytes (TIL). Depletion of CD8+ T-cells abrogated the antitumor response to the combination therapy. Furthermore, TILs isolated from SM1 tumors treated with PLX3397 and PLX4032 displayed higher immune potentiating activity.ConclusionsThe combination of BRAF-targeted therapy with CSF-1R blockade resulted in increased CD8 T-cell responses in the SM1 melanoma model, supporting the ongoing evaluation of this therapeutic combination in patients with BRAF (V600) mutant metastatic melanoma

    Inhibition of CSF-1 Receptor Improves the Antitumor Efficacy of Adoptive Cell Transfer Immunotherapy

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    Colony stimulating factor-1 (CSF-1) recruits tumor-infiltrating myeloid cells (TIMs) that suppress tumor immunity, including M2 macrophages and myeloid derived suppressor cells (MDSC). The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397. In this study, we used a syngeneic mouse model of BRAFV600E-driven melanoma to evaluate the ability of PLX3397 to improve the efficacy of adoptive T-cell therapy (ACT). In this model, we found that combined treatment produced superior anti-tumor responses compared with single treatments. In mice receiving the combined treatment, a dramatic reduction of TIMs and a skewing of MHCII(low) to MHCII(hi) macrophages was observed. Further, mice receiving the combined treatment exhibited an increase in tumor-infiltrating lymphocytes (TILs) and T cells, as revealed by real-time imaging in vivo. In support of these observations, TILs from these mice released higher levels of IFN-γ. In conclusion, CSF-1R blockade with PLX3397 improved the efficacy of ACT immunotherapy by inhibiting the intratumoral accumulation of immune suppressive macrophages
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