Thermal management of solid state power switches

The transient temperature of solid state power switches is investigated using thermal resistance network modelling and experimental testing. The ability of a heat sink mounted to the top of the device to reduce the transient temperature is assessed. Transient temperatures for heat pulses of up to 100ms are of most interest. The transient temperature distribution inside a typical stack-up of a solid state power switch is characterised. The thermal effects of adding a heat sink to the top of the device are then assessed. A variety of heat sink thicknesses and materials are evaluated. Components of the device stack-up are varied in order to assess their affect on the effectiveness of the heat sink in reducing the device temperature. Thermal networks are successfully applied to model the transient heat conduction inside the stack-ups. This modelling technique allowed a good understanding of the thermal behaviour inside the stack-up and heat sink during the transient period. The concept of using a heat sink to suppress the transient temperature was validated experimentally on two types of solid state power switch

Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes

CD38 controls the chemotaxis of leukocytes to some, but not all, chemokines, suggesting that chemokine receptor signaling in leukocytes is more diverse than previously appreciated. To determine the basis for this signaling heterogeneity, we examined the chemokine receptors that signal in a CD38-dependent manner and identified a novel "alternative" chemokine receptor signaling pathway. Similar to the "classical" signaling pathway, the alternative chemokine receptor pathway is activated by G{alpha}i2-containing Gi proteins. However, unlike the classical pathway, the alternative pathway is also dependent on the Gq class of G proteins. We show that G{alpha}q-deficient neutrophils and dendritic cells (DCs) make defective calcium and chemotactic responses upon stimulation with N-formyl methionyl leucyl phenylalanine and CC chemokine ligand (CCL) 3 (neutrophils), or upon stimulation with CCL2, CCL19, CCL21, and CXC chemokine ligand (CXCL) 12 (DCs). In contrast, G{alpha}q-deficient T cell responses to CXCL12 and CCL19 remain intact. Thus, the alternative chemokine receptor pathway controls the migration of only a subset of cells. Regardless, the novel alternative chemokine receptor signaling pathway appears to be critically important for the initiation of inflammatory responses, as G{alpha}q is required for the migration of DCs from the skin to draining lymph nodes after fluorescein isothiocyanate sensitization and the emigration of monocytes from the bone marrow into inflamed skin after contact sensitization

Thermal management of solid state power switches

The transient temperature of solid state power switches is investigated using thermal resistance network modelling and experimental testing. The ability of a heat sink mounted to the top of the device to reduce the transient temperature is assessed. Transient temperatures for heat pulses of up to 100ms are of most interest. The transient temperature distribution inside a typical stack-up of a solid state power switch is characterised. The thermal effects of adding a heat sink to the top of the device are then assessed. A variety of heat sink thicknesses and materials are evaluated. Components of the device stack-up are varied in order to assess their affect on the effectiveness of the heat sink in reducing the device temperature. Thermal networks are successfully applied to model the transient heat conduction inside the stack-ups. This modelling technique allowed a good understanding of the thermal behaviour inside the stack-up and heat sink during the transient period. The concept of using a heat sink to suppress the transient temperature was validated experimentally on two types of solid state power switch

A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury.

Multiple lines of evidence have validated the Rho pathway as important in controlling the neuronal response to growth inhibitory proteins after central nervous system (CNS) injury. A drug called BA-210 (trademarked as Cethrin(®)) blocks activation of Rho and has shown promise in pre-clinical animal studies in being used to treat spinal cord injury (SCI). This is a report of a Phase I/IIa clinical study designed to test the safety and tolerability of the drug, and the neurological status of patients following the administration of a single dose of BA-210 applied during surgery following acute SCI. Patients with thoracic (T2-T12) or cervical (C4-T1) SCI were sequentially recruited for this dose-ranging (0.3 mg to 9 mg Cethrin), multi-center study of 48 patients with complete American Spinal Injury Association assessment (ASIA) A. Vital signs; clinical laboratory tests; computed tomography (CT) scans of the spine, head, and abdomen; magnetic resonance imaging (MRI) of the spine, and ASIA assessment were performed in the pre-study period and in follow-up periods out to 1 year after treatment. The treatment-emergent adverse events that were reported were typical for a population of acute SCI patients, and no serious adverse events were attributed to the drug. The pharmacokinetic analysis showed low levels of systemic exposure to the drug, and there was high inter-patient variability. Changes in ASIA motor scores from baseline were low across all dose groups in thoracic patients (1.8±5.1) and larger in cervical patients (18.6±19.3). The largest change in motor score was observed in the cervical patients treated with 3 mg of Cethrin in whom a 27.3±13.3 point improvement in ASIA motor score at 12 months was observed. Approximately 6% of thoracic patients converted from ASIA A to ASIA C or D compared to 31% of cervical patients and 66% for the 3-mg cervical cohort. Although the patient numbers are small, the observed motor recovery in this open-label trial suggests that BA-210 may increase neurological recovery after complete SCI. Further clinical trials with Cethrin in SCI patients are planned, to establish evidence of efficacy

Visualising and Quantifying Cereal Root Responses to Phosphorus

Phosphorus (P) and nitrogen macronutrient deficiencies remain a primary constraint to global agricultural production. Expectations for decreasing fertiliser availability and increased food demand provide impetus for improving plant nutrient efficiencies. While significant genetic advances have been made based on plant shoot characteristics, the root system traits have remained largely untargeted in breeding programs. This is largely due to the difficulties in rapidly assessing root system attributes. Since the spatial distribution of the root system (root architecture) determines the edaphic resources available to plants, it is logical to target root architecture in an effort to improve plant nutrient acquisition efficiency. Characteristics such as localised root proliferation in response to high nutrient patches could be improved to increase nutrient capture from point source fertiliser applications

Internal standard-based analysis of microarray data2—Analysis of functional associations between HVE-genes

In this work we apply the Internal Standard-based analytical approach that we described in an earlier communication and here we demonstrate experimental results on functional associations among the hypervariably-expressed genes (HVE-genes). Our working assumption was that those genetic components, which initiate the disease, involve HVE-genes for which the level of expression is undistinguishable among healthy individuals and individuals with pathology. We show that analysis of the functional associations of the HVE-genes is indeed suitable to revealing disease-specific differences. We show also that another possible exploit of HVE-genes for characterization of pathological alterations is by using multivariate classification methods. This in turn offers important clues on naturally occurring dynamic processes in the organism and is further used for dynamic discrimination of groups of compared samples. We conclude that our approach can uncover principally new collective differences that cannot be discerned by individual gene analysi

Keeper Wear Mechanisms in the XIPS © 25-cm Neutralizer Cathode Assembly

Abstract: The 25-cm Xenon Ion Propulsion System (XIPS © ) thruster has been life tested for over 16,000 hours for communication satellite station keeping applications. The neutralizer cathode assembly (NCA) was observed to experience a significant amount of erosion by the end of the life test. While the NCA competed the test successfully and the life exceeds the requirement for the Boeing 702 satellite orbit-raising and station-keeping mission, erosion of the NCA keeper is a concern for longer duration NASA missions. The performance of a 25-cm neutralizer cathode has been investigated in the JPL cathode test facilities to determine the mechanisms responsible for the observed erosion in the thruster life test. Experiments with fast scanning emissive probes showed that the thruster life test started in the 4.5 kW high power mode with the neutralizer cathode operating normally in the quiescent "spot mode" where low erosion rates are observed. After 2880 hours of operation in the high power mode, the thruster operation was changed to the 2 kW low power station-keeping mode and continued in that mode for remaining 13,370 hours of the test. The emissive probe measurements indicate that the neutralizer cathode started out in the low power mode with significant plasma oscillations in the near cathode region. This behavior is indicative of "plume-mode" operation, which produces energetic ions and is well correlated to high keeper and cathode electrode erosion rates. A reduction in the neutralizer cathode orifice diameter was effective in re-establishing the spot-mode operation and eliminating the oscillations responsible for energetic ion production. Additional wear reduction can be achieved using alternative materials with lower sputtering yields. A wear test is now underway of a modified version of this neutralizer cathode that incorporates the smaller orifice diameter and a replacement of the standard molybdenum keeper material by tantalum. The wear test, combined with JPL's validated neutralizer cathode life models, is intended to show that the erosion rate of the present keeper and of the smaller cathode-plate orifice is insignificant thereby demonstrating sufficient neutralizer life for deep space missions

Canonical Wnt signals combined with suppressed TGFβ/BMP pathways promote renewal of the native human colonic epithelium

Background: A defining characteristic of the human intestinal epithelium is that it is the most rapidly renewing tissue in the body. However, the processes underlying tissue renewal and the mechanisms that govern their coordination have proved difficult to study in the human gut. Objective: To investigate the regulation of stem cell-driven tissue renewal by canonical Wnt and TGFβ/bone morphogenetic protein (BMP) pathways in the native human colonic epithelium. Design: Intact human colonic crypts were isolated from mucosal tissue samples and placed into 3D culture conditions optimised for steady-state tissue renewal. High affinity mRNA in situ hybridisation and immunohistochemistry were complemented by functional genomic and bioimaging techniques. The effects of signalling pathway modulators on the status of intestinal stem cell biology, crypt cell proliferation, migration, differentiation and shedding were determined. Results: Native human colonic crypts exhibited distinct activation profiles for canonical Wnt, TGFβ and BMP pathways. A population of intestinal LGR5/OLFM4-positive stem/progenitor cells were interspersed between goblet-like cells within the crypt-base. Exogenous and crypt cell-autonomous canonical Wnt signals supported homeostatic intestinal stem/progenitor cell proliferation and were antagonised by TGFβ or BMP pathway activation. Reduced Wnt stimulation impeded crypt cell proliferation, but crypt cell migration and shedding from the crypt surface were unaffected and resulted in diminished crypts. Conclusions: Steady-state tissue renewal in the native human colonic epithelium is dependent on canonical Wnt signals combined with suppressed TGFβ/BMP pathways. Stem/progenitor cell proliferation is uncoupled from crypt cell migration and shedding, and is required to constantly replenish the crypt cell population

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

Structural design of contact lens-based drug delivery systems; in vitro and in vivo studies of ocular triggering mechanisms

This study identifies and investigates the potential use of in-eye trigger mechanisms to supplement the widely available information on release of ophthalmic drugs from contact lenses under passive release conditions. Ophthalmic dyes and surrogates have been successfully employed to investigate how these factors can be drawn together to make a successful system. The storage of a drug-containing lens in a pH lower than that of the ocular environment can be used to establish an equilibrium that favours retention of the drug in the lens prior to ocular insertion. Although release under passive conditions does not result in complete dye elution, the use of mechanical agitation techniques which mimic the eyelid blink action in conjunction with ocular tear chemistry promotes further release. In this way differentiation between passive and triggered in vitro release characteristics can be established. Investigation of the role of individual tear proteins revealed significant differences in their ability to alter the equilibrium between matrix-held and eluate-held dye or drug. These individual experiments were then investigated in vivo using ophthalmic dyes. Complete elution was found to be achievable in-eye; this demonstrated the importance of that fraction of the drug retained under passive conditions and the triggering effect of in-eye conditions on the release process. Understanding both the structure-property relationship between drug and material and in-eye trigger mechanisms, using ophthalmic dyes as a surrogate, provides the basis of knowledge necessary to design ocular drug delivery vehicles for in-eye release in a controllable manner