118 research outputs found

    Low power, compact charge coupled device signal processing system

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    A variety of charged coupled devices (CCDs) for performing programmable correlation for preprocessing environmental sensor data preparatory to its transmission to the ground were developed. A total of two separate ICs were developed and a third was evaluated. The first IC was a CCD chirp z transform IC capable of performing a 32 point DFT at frequencies to 1 MHz. All on chip circuitry operated as designed with the exception of the limited dynamic range caused by a fixed pattern noise due to interactions between the digital and analog circuits. The second IC developed was a 64 stage CCD analog/analog correlator for performing time domain correlation. Multiplier errors were found to be less than 1 percent at designed signal levels and less than 0.3 percent at the measured smaller levels. A prototype IC for performing time domain correlation was also evaluated

    Programming Protocol-Independent Packet Processors

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    P4 is a high-level language for programming protocol-independent packet processors. P4 works in conjunction with SDN control protocols like OpenFlow. In its current form, OpenFlow explicitly specifies protocol headers on which it operates. This set has grown from 12 to 41 fields in a few years, increasing the complexity of the specification while still not providing the flexibility to add new headers. In this paper we propose P4 as a strawman proposal for how OpenFlow should evolve in the future. We have three goals: (1) Reconfigurability in the field: Programmers should be able to change the way switches process packets once they are deployed. (2) Protocol independence: Switches should not be tied to any specific network protocols. (3) Target independence: Programmers should be able to describe packet-processing functionality independently of the specifics of the underlying hardware. As an example, we describe how to use P4 to configure a switch to add a new hierarchical label

    Intensivmedizinische Behandlung von Erwachsenen mit angeborenen Herzfehlern

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    Zusammenfassung: Dank Verbesserungen in der Herzchirurgie und der perioperativen Betreuung steigt die Anzahl der Erwachsenen mit einem angeborenen Herzfehler stetig. Die perioperative und intensivmedizinische Betreuung dieser Patienten stellt aufgrund der vielen verschiedenen Pathologien und chirurgischen Möglichkeiten sowie der komplexen Pathophysiologie eine Herausforderung dar. Viele Patienten entwickeln mit der Zeit Organdysfunktionen und viele von ihnen benötigen Folgeoperationen am Herzen sowie nichtkardiale Eingriffe im Erwachsenalter. Aufgrund der Komplexität sind diese Patienten in spezialisierten tertiären Krankenhäusern zu behandeln, die über ein disziplinenübergreifendes Fachwissen verfügen. Da dies in Notfällen nicht immer möglich sein wird, sind grundlegende Kenntnisse dieser Patientengruppe für in der Akutversorgung Tätige wichtig. In dieser Übersicht werden allgemeine Aspekte, wie pulmonale Hypertonie, Eisenmenger-Syndrom, Zyanose, Schwangerschaft und perioperative Betreuung, behandelt. Ein besonderes Augenmerk gilt dabei der intensivmedizinischen Versorgung von kritisch kranken Patienten mit angeborenen Herzfehler

    Arginine deficiency augments inflammatory mediator production by airway epithelial cells in vitro

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    <p>Abstract</p> <p>Background</p> <p>Previously we showed that reduced availability of the essential amino acid tryptophan per se attenuates post-transcriptional control of interleukin (IL)-6 and IL-8 leading to hyperresponsive production of these inflammatory mediators by airway epithelial cells. Availability of the non-essential amino acid arginine in the inflamed airway mucosa of patients with asthma is reduced markedly, but it is not known whether this can also lead to an exaggerated production of IL-6 and IL-8.</p> <p>Methods</p> <p>IL-6 and IL-8 were determined by ELISA in culture supernatants of NCI-H292 airway epithelial-like cells and normal bronchial epithelial (NHBE) cells that were exposed to TNF-α, LPS or no stimulus, in medium with or without arginine. Arginine deficiency may also result from exposure to poly-L-arginine or major basic protein (MBP), which can block arginine uptake. Epithelial cells were exposed to these polycationic proteins and L-<sup>14</sup>C-arginine uptake was assessed as well as IL-6 and IL-8 production. To determine the mode of action, IL-6 and IL-8 mRNA profiles over time were assessed as were gene transcription and post-transcriptional mRNA degradation.</p> <p>Results</p> <p>For both NCI-H292 and NHBE cells, low arginine concentrations enhanced basal epithelial IL-6 and IL-8 production and synergized with TNF-α-induced IL-6 and IL-8 production. Poly-L-arginine enhanced the stimulus-induced IL-6 and IL-8 production, however, blocking arginine uptake and the enhanced IL-6 and IL-8 production appeared unrelated. The exaggerated IL-6 and IL-8 production due to arginine deficiency and to poly-L-arginine depend on a post-transcriptional and a transcriptional process, respectively.</p> <p>Conclusion</p> <p>We conclude that both reduced arginine availability per se and the presence of polycationic proteins may promote airway inflammation by enhanced pro-inflammatory mediator production in airway epithelial cells, but due to distinct mechanisms.</p

    The Glycan Shield of HIV Is Predominantly Oligomannose Independently of Production System or Viral Clade

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    The N-linked oligomannose glycans of HIV gp120 are a target for both microbicide and vaccine design. The extent of cross-clade conservation of HIV oligomannose glycans is therefore a critical consideration for the development of HIV prophylaxes. We measured the oligomannose content of virion-associated gp120 from primary virus from PBMCs for a range of viral isolates and showed cross-clade elevation (62–79%) of these glycans relative to recombinant, monomeric gp120 (∼30%). We also confirmed that pseudoviral production systems can give rise to notably elevated gp120 oligomannose levels (∼98%), compared to gp120 derived from a single-plasmid viral system using the HIVLAI backbone (56%). This study highlights differences in glycosylation between virion-associated and recombinant gp120

    Basolateral Sorting of Syntaxin 4 Is Dependent on Its N-terminal Domain and the AP1B Clathrin Adaptor, and Required for the Epithelial Cell Polarity

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    Generation of epithelial cell polarity requires mechanisms to sort plasma membrane proteins to the apical and basolateral domains. Sorting involves incorporation into specific vesicular carriers and subsequent fusion to the correct target membranes mediated by specific SNARE proteins. In polarized epithelial cells, the SNARE protein syntaxin 4 localizes exclusively to the basolateral plasma membrane and plays an important role in basolateral trafficking pathways. However, the mechanism of basolateral targeting of syntaxin 4 itself has remained poorly understood. Here we show that newly synthesized syntaxin 4 is directly targeted to the basolateral plasma membrane in polarized Madin-Darby canine kidney (MDCK) cells. Basolateral targeting depends on a signal that is centered around residues 24–29 in the N-terminal domain of syntaxin 4. Furthermore, basolateral targeting of syntaxin 4 is dependent on the epithelial cell-specific clathrin adaptor AP1B. Disruption of the basolateral targeting signal of syntaxin 4 leads to non-polarized delivery to both the apical and basolateral surface, as well as partial intercellular retention in the trans-Golgi network. Importantly, disruption of the basolateral targeting signal of syntaxin 4 leads to the inability of MDCK cells to establish a polarized morphology which suggests that restriction of syntaxin 4 to the basolateral domain is required for epithelial cell polarity

    Discovery and Development of Toll-Like Receptor 4 (TLR4) Antagonists: A New Paradigm for Treating Sepsis and Other Diseases

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    Abstract. Sepsis remains the most common cause of death in intensive care units in the USA, with a current estimate of at least 750,000 cases per year, and 215,000 deaths annually. Despite extensive research still we do not quite understand the cellular and molecular mechanisms that are involved in triggering and propagation of septic injury. Endotoxin (lipopolysaccharide from Gram-negative bacteria, or LPS) has been implicated as a major cause of this syndrome. Inflammatory shock as a consequence of LPS release remains a serious clinical concern. In humans, inflammatory responses to LPS result in the release of cytokines and other cell mediators from monocytes and macrophages, which can cause fever, shock, organ failure and death. A number of different approaches have been investigated to try to treat and/or prevent the septic shock associated with infections caused by Gram-negative bacteria, including blockage of one or more of the cytokines induced by LPS. Recently several novel amphipathic compounds have been developed as direct LPS antagonists at the LPS receptor, TLR4. This review article will outline the current knowledge on the TLR4-LPS synthesis and discuss the signaling, in vitro pre-clinical and in vivo clinical evaluation of TLR4 antagonists and their potential use in sepsis and a variety of diseases such as atherosclerosis as well as hepatic and renal malfunction. KEY WORDS: drug discovery; LPS; sepsis; toll-like receptor antagonists

    The provenance of Borneo's enigmatic alluvial diamonds:A case study from Cempaka, SE Kalimantan

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    Gem-quality diamonds have been found in several alluvial deposits across central and southern Borneo. Borneo has been a known source of diamonds for centuries, but the location of their primary igneous source remains enigmatic. Many geological models have been proposed to explain their distribution, including: the diamonds were derived from a local diatreme; they were brought to the surface through ophiolite obduction or exhumation of UHP metamorphic rocks; they were transported long distances southward via major Asian river systems; or, they were transported from the Australian continent before Borneo was rifted from its northwestern margin in the Late Jurassic. To assess these models, we conducted a study of the provenance of heavy minerals from Kalimantan's Cempaka alluvial diamond deposit. This involved collecting U–Pb isotopic data, fission track and trace element geochemistry of zircon as well as major element geochemical data of spinels and morphological descriptions of zircon and diamond. The results indicate that the Cempaka diamonds were likely derived from at least two sources, one which was relatively local and/or involved little reworking, and the other more distal which records several periods of reworking. The distal diamond source is interpreted to be diamond-bearing pipes that intruded the basement of a block that: (1) rifted from northwest Australia (East Java or SW Borneo) and the diamonds were recycled into its sedimentary cover, or: (2) were emplaced elsewhere (e.g. NW Australia) and transported to a block (e.g. East Java or SW Borneo). Both of these scenarios require the diamonds to be transported with the block when it rifted from NW Australia in the Late Jurassic. The local source could be diamondiferous diatremes associated with eroded Miocene high-K alkaline intrusions north of the Barito Basin, which would indicate that the lithosphere beneath SW Borneo is thick (~ 150 km or greater). The ‘local’ diamonds could also be associated with ophiolitic rocks that are exposed in the nearby Meratus Mountains

    Agent-Based Modeling of Endotoxin-Induced Acute Inflammatory Response in Human Blood Leukocytes

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    Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions.An agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades.The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve our understanding of how manipulating the behavior of the molecular species could manifest into emergent behavior of the overall system
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