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Outsourcing is described as the strategic use of external resources to carry out tasks that have traditionally been performed by internal staff and resources. It is considered to be the best-known phenomena of modern times and business strategy to drive the global economy. Outsourcing offers enormous benefits to companies only if the outsourcing decision is correct and factors that affect the outsourcing decision are adequately considered, otherwise irreparable harm may be caused. A study to identify the critical success factors of IT outsourcing in Nepal from the vendor's perspective has been initiated. This study examines different models about the effectiveness of outsourcing for the reason. All these models have their own advantages and drawbacks, so a careful review is important to reach at conclusions for the organizations that wish to follow such models. This article is based on4 comprehensive literature review of the success factors for outsourcing that led to the discovery of six different outsourcing models. The study has reviewed Leavitt’s model, McKinsey 7-S framework, The Nadler-Tushman Congruence Model, Technology Acceptance Model, DeLone and McLean's IS-Success Model and IS-Impact Model. Revised DeLone and McLean Model of Information Systems Success, however, are widely debated and considered to be the most promising.

More and more computing services are running in clouds as the number and scope of internet services are increasing exponentially. Major objective of cloud computing is to give users virtually unlimited pay per use computing resources without any concern for managing the underlying infrastructure. But this results in huge increase in size of computing environment which makes it very difficult to measure the performance of allocation strategies that use the description of underlying infrastructure and resource dependency graphs for making decisions. Both dynamic and static allocation strategies have their share of advantages and drawbacks. In this paper we will try to define a hybrid scheme for resource allocation that will use the positive features of both schemes to give better performance.

Consumers were asked to indicate a flavor and texture preference for one of two creamed and salted small-curd cottage cheeses made by direct-acid-set or conventional short-set culture methods. When a commercial starter distillate flavor was added to direct-acid-set cheese, its flavor and texture were preferred over cheese made by the culture method. Conversely, when flavor was not added to the direct-acid-set cheese, consumers preferred the flavor and texture of the cultured product. Differences among mean flavor or texture scores of three age groups were not significant (20, 20-40,40). Preferences for texture appeared to be biased by flavor.

Deposition potential, deposition time, square wave frequency, rotation speed of the rotating disc electrode, and palladium concentration were studied on a Glassy Carbon Electrode (GCE) in 0.01M HCl for the determination of palladium in High Level Nuclear Waste (HLNW) by anodic stripping voltammetry. Experimental conditions were optimized for the determination of palladium at two different, 10 -8 and 10 -7 M, levels. Error and standard deviation of this method were under 1% for all palladium standard solutions. The developed technique was successfully applied as a subsidiary method for the determination of palladium in simulated high level nuclear waste with very good precision and high accuracy (under 1 % error and standard deviation).

The aims of this study were to characterise the composition of seaweed species and to evaluate the efficacy of aqueous extracts as plant biostimulants. Five species (Ascophyllum nodosum, Fucus serratus, Fucus vesiculosus, Laminaria hyperborea and Sargassum muticum) of seaweed were harvested from Strangford Lough, Northern Ireland for the evaluation of polysaccharides, indole-3-acetic acid (IAA), carbon, nitrogen, lipid, ash and mineral contents. The compositional analyses of the five species and their freeze-dried extracts were also carried out using thermogravimetric analysis, scanning electron microscopy and X-ray microanalysis. The concentration of IAA in the acid extracts of the five species ranged between 2.74 and 46.8 ng g−1. The carbon, nitrogen, lipid and ash contents ranged between 25.0 and 38.6, 1.37%, and 3.16, 0.83%, and 3.98 and 18.10 and 47.68%, respectively. L. hyperborea and S. muticum contained the highest amounts of minerals. The biostimulant activities of acidic (pH 3.0), neutral (pH 6.5) and alkaline (pH 9.0) extracts were determined by mung bean bioassay. The alkaline extracts from F. vesiculosus and A. nodosum stimulated significantly (P

We have investigated the selective etching of 50 μm diameter via-holes for etch depth >200 μm using 30 μm thick photo resist mask in Inductively Coupled Plasma system with Cl 2 /BCl 3 chemistry. Resultant etch rate/etch profiles are studied as a function of ICP process parameters and photo resist mask sidewall profile. Etch yield and aspect ratio variation with process pressure and substrate bias is also investigated at constant ICP power. The etch yield of ICP process increased with pressure due to reactant limited etch mechanism and reached a maximum of ∼19 for 200 μm depth at 50 mTorr pressure, 950 W coil power, 80 W substrate bias with an etch rate ∼4.9 μm/min. Final aspect ratio of etched holes is increased with pressure from 1.02 at 20 mTorr to 1.38 at 40 mTorr respectively for fixed etch time and then decreased to 1.24 at 50 mTorr pressure. The resultant final etch profile and undercut is found to have a strong dependence on the initial slope of photo resist mask sidewall angle and its selectivity in the pressure range of 20–50mTorr.

This study investigates the dry etching of 60 mm dia, 200 mm deep holes for fabrication of through substrate via holes for grounding monolithic microwave integrated circuits (MMICs), on 3-inch dia semiinsulating GaAs wafer using RIE and ICP processes with CFC and non-CFC gas chemistry, respectively. The effect of various process parameters on GaAs etch rate and resultant etch profile was investigated. Two kinds of masks, photoresist and Ni, were used to etch GaAs and performance was compared by investigating effect on etch rate, etch depth, etch profile, and surface morphology. The etch profile, etch depth, and surface morphology of as-etched samples were characterised by scanning electron microscopy. The desired 200 mm deep strawberry profile was obtained at 40 mTorr for both RIE and ICP processes with an etch rate of ~1.3 mm/min and ~4 mm/min respectively. Ni metal mask was used for RIE process due to poor photoresist selectivity, whereas ICP process utilised photoresist as mask. The vias were then metallised by depositing a thin seed layer of Ti/Au (1000 A) using radio frequency sputtering and Au (~5 mm) electroplated to connect the frontside pad and back side ground plane. The typical parasitic inductance offered by these via for RIE and ICP processes was ~76 pH and 83 pH respectively, which is well within the acceptable limits. The developed process was finally integrated to in-house MMIC production line. Defence Science Journal, 2009, 59(4), pp.363-370 , DOI:http://dx.doi.org/10.14429/dsj.59.1535

Deposition potential, deposition time, square-wave frequency, rotation speed of the rotating disc electrode and gallium concentration have been studied in detail, for trace concentration level determination of gallium metal in U–Ga alloy by square-wave voltammetry anodic stripping analysis, in 1 M NaClO4 + 0.5 M NaSCN at mercury film electrode (MFE). Optimum conditions have been found for Ga(III) determination by obtaining calibration graphs for the range 1–10 × 10−7 M gallium. Error and standard deviation less than 1% were assessed of this method with all gallium standard solutions. The developed methodology was applied successfully as a subsidiary method for the determination of gallium content in synthetic U–Ga samples with very good precision and accuracy (under 1% error and std. dev.).

Controlled potential coulometric (CPC) studies were carried out for developing a method to determine gallium at milligram levels, in the mixed supporting electrolyte medium (4 M NaClO 4 + 0.5 M NaSCN), employing stirring mercury as a working electrode. Investigations for optimization of working electrode potentials, quantity of charge, level of background current and electrolysis time for achieving quantitative reduction of Ga(III) to Ga and its oxidation back to Ga(III), were undertaken. Effect of gallium content and interference of zinc in of gallium determination were also studied. The developed methodology was employed for the determination of gallium in pure Ga as well as in synthetic U + Ga mixture solutions. Accuracy and precision values of better than 0.5% were obtained at 1–2 mg levels.

BACKGROUND: Ongoing inflammatory processes resulting in airway and vascular remodelling characterise chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1) could play a role in tissue remodelling and angiogenesis in COPD. METHODS: The cellular expression pattern of VEGF, Flt-1, and KDR/Flk-1 was examined by immunohistochemistry in central and peripheral lung tissues obtained from ex-smokers with COPD (forced expiratory volume in 1 second (FEV(1)) 85% predicted; n = 14). The immunohistochemical staining of each molecule was quantified using a visual scoring method with grades ranging from 0 (no) to 3 (intense). RESULTS: VEGF, Flt-1, and KDR/Flk-1 immunostaining was localised in vascular and airway smooth muscle (VSM and ASM) cells, bronchial, bronchiolar and alveolar epithelium, and macrophages. Pulmonary endothelial cells expressed Flt-1 and KDR/Flk-1 abundantly but not VEGF. Bronchial VEGF expression was higher in microvascular VSM cells and ASM cells of patients with COPD than in patients without COPD (1.7 and 1.6-fold, p

Supplement - Rasendramangalam of Nagarjuna

Flow of Compressible Fluid through an Elliptic Pipe

Adrenaline (ADR) and vasopressin (VAS) are used as vasopressors during cardiopulmonary resuscitation. Data regarding their effects on blood-brain barrier (BBB) integrity and neuronal damage are lacking. We hypothesised that VAS given during cardiopulmonary resuscitation (CPR) after haemorrhagic circulatory arrest will preserve BBB integrity better than ADR.Twenty-one anaesthetised sexually immature male piglets (with a weight of 24.3 ± 1.3 kg) were bled 35% via femoral artery to a mean arterial blood pressure of 25 mmHg in the period of 15 min. Afterwards, the piglets were subjected to 8 min of untreated ventricular fibrillation followed by 15 min of open-chest CPR. At 9 min of circulatory arrest, piglets received amiodarone 1.0 mg/kg and hypertonic-hyperoncotic solution 4 ml/kg infusions for 20 min. At the same time, VAS 0.4 U/kg was given intravenously to the VAS group (n = 9) while the ADR group received ADR 20 μg/kg (n = 12). Internal defibrillation was attempted from 11 min of cardiac arrest to achieve restoration of spontaneous circulation. The experiment was terminated 3 h after resuscitation.The intracranial pressure (ICP) in the post-resuscitation phase was significantly greater in ADR group than in VAS group. VAS group piglets exhibited a significantly smaller BBB disruption compared with ADR group. Cerebral pressure reactivity index showed that cerebral blood flow autoregulation was also better preserved in VAS group.Resuscitation with ADR as compared with VAS after haemorrhagic circulatory arrest increased the ICP and impaired cerebrovascular autoregulation more profoundly, as well as exerted an increased BBB disruption though no significant difference in neuronal injury was observed.

A Gunn diode is a simple two terminal source of low-noise, high frequency microwave power. It is most commonly used as local oscillator in critical microwave and mm-wave systems. The system requirement of frequency agility and temperature stability impose stringent demands on the device performance and hence on its material and fabrication technology. The present paper discusses some of the technological innovations attempted in this direction along with results obtained. Some of the issues addressed are carrier concentration ramping to check velocity degradation in the active layer, power optimisation by in-situ etching, minimisation of dead zone and thermal management. Physics, design and fabrication technology and testing of Gunn diodes is also briefly described in this article.

Rf sputtered Ti/Pt/Au Schottky contacts with varying titanium thickness have been made on (n)GaAs by the lift-off process under actual device processing conditions. The ideality factor of the Schottky barrier is dose to unity (∼ 1.07) with a barrier height of 0.80 ± 0.02 eV. The contacts with Ti films as thin as 100 A remain thermally stable with annealing up to 400°C. These contacts have been next used to fabricate submicron gate length GaAs MESFETs. The MESFET's gm increases with improved gate diode ideality but is not a strong function of it. The effect of Schottky gate annealing on the MESFET's dc characteristics shows that IDSS, gm, Vp and VR(GS) remain stable with annealing upto 350°C and degrade with 400° anneal.

AIMS/BACKGROUND The late stages of age-related maculopathy (ARM), especially neovascular macular degeneration (ARMD), can severely affect central vision and are the main cause of blindness in the elderly in the Western world. It has been shown that angiogenic growth factors are present in neovascular membranes in ARMD. However, it is not known if angiogenic growth factors play a role in the onset of neovascularisation. METHODS In order to elucidate the involvement of angiogenic growth factors in the initiation of neovascularisation in early stages of ARM, the expression patterns of VEGF, TGF-β, b-FGF, and PDGF-AA on 18 human maculae with ARM, and on 11 control specimens were investigated immunohistochemically. RESULTS A significantly increased expression of VEGF (p=0.00001) and TGF-β (p=0.019) was found in the retinal pigment epithelium (RPE) of maculae with ARM compared with control maculae. Furthermore, an increased expression of VEGF and PDGF was found in the outer nuclear layer of maculae with ARM. CONCLUSION These results demonstrate an increased expression of VEGF in the RPE, and in the outer nuclear layer in maculae with ARM, that could be involved in the pathogenesis of neovascular macular degeneration. Furthermore, enhanced TGF-β expression in the RPE cells of maculae with early stages of ARM was shown.

This chapter deals with the micro-climatic changes and some of man-induced environmental hazards of the Indian arid regions. The study of rainfall trends for the last 100 years in Rajasthan shows that certain stations have recently experienced apparent downward trend in rainfall, whereas others have shown a high variability from year to year, but no constant trend has yet been noticed. Some studies in Rajasthan show that there has been an increasing trend of rainfall in western part and a decreasing trend in the eastern part of the Aravallis in the last 50 years. Recurring drought and acceleration of desertification processes; drinking water scarcity; occurrence of brackish groundwater; presence of fluoride in the groundwater in most parts of the desert; salinity hazards; water logging and rising water table in the vicinity of canal-irrigated areas, especially Indira Gandhi Nahar Pariyojana (IGNP) and high flood propensity, in desert districts; destruction of natural vegetation by deforestation for fuel and fodder; mining activities and overgrazing; creation of scarred and derelict landscape due to open cast mining of minerals and raw material resources and depletion of biodiversity and stress on wildlife habitat are some of the geo-environmental hazards which need immediate attention.

The paper describes design and fabrication of GaAs I()(} mW Gunn diodes for operation at -35 GHz. As the devices have low efficiency, a large amount of input power is dissipated as heat, resulting in temperature rise in the device during operation beyond tolerable limits. Heat from these devices can be removed quickly and efficiently by using gold as integral heat sink (IHS). Further, the temperature of the device can be controlled by monitoring device area. Calculations for heat flow and expected efficiency have been done. Required Gunn structure has been grown by molecular beam epitaxy technique. The devices have been fahricated by IHS-IBR (integral bonding ribbon) technique. From the devices developed, 100 mW of output has been achieved in the frequency range 33-38 GHz with an efficiency of 3-4 per cent. semiconductors which have a multivalley structure in their conduction hand. Gallium arsenidc is the main rcpresentative of this class. When a thin sample of this material is hiased, the current increases linearly with hiasing voltage following Ohm's law. As the hias voltage increases heyond the threshold voltage, the current starts decreasing giving rise to negative differential resistance; and current oscillations in the circuit are oh served. The decrease in current is found to he

Discrete millimetre-wave devices, i.e. Gunn and IMPATT diodes, dissipate a large amount of power in the form of heat. Devices fabricated with an integral heat sink (IHS) are known to show superior performance compared with conventional devices. A novel process was developed for the fabrication of IHS integral bonding ribbon (IBR) millimetre-wave devices. The method employs “through holes” generated on the wafer as marks for “front to back” alignment of the IHS and IBR. The process is found to be highly reproducible and versatile. Devices have shown several advantages in terms of ease of processing and yield. The process can thus be used to fabricate devices different semiconductor materials and possibly for all devices requiring the IHS-IBR configuration.

Poor adhesion of the metal to the dielectric film may lead to loss of the device or circuit in the final stages of fabrication, for instance bonding. The present experimental study was carried out to improve metal adhesion over polyimides and Si 3 N x and SiO x grown by plasma-enhanced chemical vapour deposition. The metal lines were formed by depositing multilayer films by r.f. sputtering followed by electroplating of gold in some cases. The samples with poor metal-dielectric adhesion showed bubbling or blistering in the metal layer when subjected to temperature cycles in the subsequent process steps. The experimental study proved that in addition to the r.f. sputtering parameters and the premetallization treatment, the thickness of the first metal layer in the multilayer metal scheme is critical to adhesion.

Neurobiology of the CNS injury and repair: New roles of amino acids,growth factors and neuropeptides -- introduction.

The possibility that prostaglandins participate in opening of the blood-spinal cord barrier (BSCB) after trauma was investigated by comparing rats given indomethacin (an inhibitor of prostaglandin synthesis) before trauma with untreated animals. The trauma was produced by making an incision into the right dorsal horn of the T10-11 segment. The BSCB was examined after 5 h using Evans blue, [131I]-sodium and lanthanum as tracers. A focal trauma to the cord resulted in widespread opening of the BSCB to [l3lI]-sodium in the C5 to L5 segments of the untreated rats. Evans blue extravasation was limited to the T9-T12 segments. Electron microscopy of microvessels in the T9 and T12 segments showed lanthanum diffusely in some endothelial cells, in vesicular profiles and basal lamina. On the other hand, indomethacin pretreatment prevented the extravasation of [131I]-sodium in segments located far away from the trauma. In segments closer to the trauma, the extravasation of radiotracer was markedly reduced. Extravasation of Evans blue was less pronounced. Spread of lanthanum into the basal lamina of microvessels was not present. The diffuse passage into the capillary endothelium was reduced and the incidence of cytoplasmic vesicles loaded with lanthanum was lower. Our results for the first time provide direct morphological evidence that prostaglandins are involved in the early, widespread opening of the BSCB after trauma to the cord.

The potential efficacy of indomethacin (a potent inhibitor of endogenous prostaglandin synthesis) on spinal cord-evoked potentials and edema formation occurring after a focal trauma to the spinal cord was examined in a rat model. The spinal cord evoked potentials were recorded in urethane-anesthetized male rats using monopolar electrodes placed epidurally over the T9 (rostral) and T12 (caudal) segments after stimulation of the ipsilateral right tibial and sural nerves. Reference electrodes were placed in the corresponding paravertebral muscles. The spinal cord evoked potential consisted of a small positive peak followed by a broad and high negative peak. Amplitudes and latencies of the maximal positive peak and the maximal negative peak were measured. The latencies and amplitudes 30 min before injury were used as references (100%). A complete loss was denoted as 0%. All the potentials were quite stable during 30 min of recording before injury. Infliction of trauma to the T10-T11 segments of the spinal cord with a sterile scalpel blade (about 5 mm longitudinal and 2 mm deep incision into the right dorsal horn extending to Rexed's laminae VII) in untreated animals resulted in an immediate depression of the rostral maximal negative peak amplitude (60-100%) which persisted during 5 h of recording. The latencies of the rostral as well as caudal maximal negative and positive peaks increased successively from 2 h post-trauma. In this group of animals, 5 h after injury the spinal cord water content in the traumatized segments was increased by more than 6% as compared with a group of uninjured animals. Pretreatment with indomethacin (10 mg/kg body weight i.p. 30 min before injury) markedly attenuated the immediate decrease in the maximal negative peak amplitude after injury, but did not influence the successive latency increase. However, the increase in the water content of the traumatized cord after 5 h was less pronounced compared with untreated injured rats. Our results show a beneficial effect of indomethacin on trauma-induced spinal cord evoked potential changes and edema formation. Prostaglandins may thus influence early bioelectrical changes occurring in traumatized spinal cord not reported earlier. The findings support the view that early recording of spinal cord evoked potential may be useful to predict the outcome in some forms of spinal cord injuries.

Graphite has been employed as a working electrode in the controlled potential coulometric determination of uranium and plutonium. The couples U(VI)/U(IV) and Pu(IV)/Pu(III) employed for analysis have diverse redox potentials and commonly the working electrodes employed are mercury and platinum. A graphite electrode in the shape of a beaker showed satisfactory performance for the quantitative reduction of U(VI) to U(IV) and Pu(IV) to Pu(III) and also for quantitative oxidation of Pu(III) to Pu(IV). Studies on the levels of the background current, blank values and their reproducible behaviour in acid media have been carried out with a view to achieve good precision and accuracy. A software-based predictive evaluation technique of end-point charge has been investigated. The results have shown that the graphite electrode can be used for the determination of both uranium and plutonium in the presence of each other with a precision and accuracy of better than ±0.5%.

To understand the complex mechanism(s) involved in molecular responses to ischemia, we developed two experimental models in pigs. In a "stunning" model of repetitive ischemia and reperfusion, we studied the mRNA expression of immediate early genes like c-fos, c-myc and heat shock protein-70 (HSP-70). Myocardial stunning was achieved by two cycles of 10-min left anterior descending coronary artery (LAD) occlusion and 30 min reperfusion. We observed several-fold enhanced expression of c-fos and HSP-70 mRNA in the stunned myocardium as compared with the control, whereas c-myc mRNA levels remained almost unchanged. In the second model, we examined the expression of the peptide mitogens heparin-binding growth factor 1 (HBGF-1) and transforming growth factor beta 1 (TGF-beta 1) after a chronic coronary artery occlusion leading to myocardial collateralization. Progredient stenosis of the circumflex coronary artery was induced by implanting a hygroscopic ameroid constrictor ring around it and occlusion was verified by in vivo angiography. Using polymerase chain reaction (PCR) and Northern hybridization techniques, we observed significantly enhanced expression of HBGF-1 and TGF-beta 1 in collateralized myocardium as compared with normal. In situ techniques revealed the localization of HBGF-1 transcripts in the blood vessel wall, and TGF-beta 1 in cardiac myocytes and Purkinje cells. Our results clearly indicate that myocardial stunning stimulates the expression of transcription factors which might be involved in regulation of certain growth factors like HBGF-1 and TGF-beta 1 which may play a significant role in the development of a collateral circulation.

The possibility that astrocytes participate in the pathophysiology of thermal brain injury caused by systemic heat exposure was examined in conscious young rats. The temporal and regional pattern of the astrocytic response to thermal injury was characterized by demonstrating the immunoreactivity of glial fibrillary acidic protein (GFAP) using monoclonal antibody and avidin-biotin complex technique. Exposure of conscious young animals to heat at 38 degrees C for 4 h in a biological oxygen demand incubator resulted in a marked increase of the GFAP immunoreactivity in specific brain regions as compared with the intact controls. The intensity of the increased GFAP immunoreactivity was mainly noted in pons, medulla and cerebellum, followed by thalamus, hypothalamus, hippocampus and caudate nucleus. The cerebral cortex of heat-exposed animals showed only a mild increase in GFAP immunoreactivity which was predominantly concentrated in cingulate, parietal and pyriform cortices. The immunostaining in general was seen in the perivascular glia, within the neuropil and the glia limitans. This increase in GFAP immunoreactivity was absent in animals exposed to the same ambient temperature (38 degrees C) for 1 h and 2 h, or at a lower temperature (36 degrees C) for 4 h. These results show that (i) astrocytes actively participate in the pathophysiology of heat stress, (ii) endogenous thermal brain injury elicits activation and hypertrophy of astrocytes ("reactive gliosis") depending on the magnitude and duration of the ambient heat stimulus, and (iii) the astrocytic reaction (observed as increased GFAP immunostaining) could be induced much more rapidly within a very short survival period of 4 h, not reported earlier.

The potential neuroprotective efficacy of dynorphin A antiserum on BBB dysfunction, edema formation and brain pathology was examined in a closed head injury (CHI) model in the rat. The CHI was produced by an impact of 0.224 N on the right parietal bone under anesthesia by dropping a weight of 114.6 g on the skull from a height of 20 cm through a guide tube. This concussive brain injury resulted in profound BBB disruption as evidenced by leakage of Evans blue and radioiodine in the brain. Edema formation and swelling at 5 h were most pronounced in the contralateral cerebral hemisphere. Pretreatment with dynorphin A antiserum (1:20, monoclonal) infused into the left lateral cerebral ventricle (30 microL in PBS) either 30 min before or 30 min after CHI significantly attenuated BBB dysfunction, brain edema formation, volume swelling and brain pathology. However, no reduction in brain edema, BBB permeability or improved brain pathology was seen when the antiserum was given 60 min post-CHI. These observations are the first to suggest that antiserum to dynorphin when administered into the CSF during early phase of CHI is neuroprotective. Our work further indicates that dynorphin is actively involved in the cellular and molecular mechanisms of edema formation and BBB breakdown in CHI.

The permeability of blood vessels in rat spinal nerve roots was investigated with Evans blue-albumin as an in vivo macromolecular tracer and lanthanum nitrate as an electron microscopic ionic marker added to a fixative. Rats injected intravenously with Evans blue, showed macroscopic distinct staining of dorsal root ganglia, whereas spinal nerve roots remained unstained. Fluorescence microscopy, however, revealed clear extravascular fluorescence both in ventral and dorsal roots 2 or 18 h after tracer administration. Two different types of blood vessels exists in spinal nerve roots; large extrinsic (radicular) in the root sheath and minute intrinsic vessels in the parenchyma. Lanthanum added to a fixative, perfused through the vessels was detected in the lumen of both types of vessels, usually adhering to the luminal plasma membrane and in many invaginations from that membrane. Lanthanum also entered the clefts between endothelial cells but was always stopped at the junctions which are, thus, of the tight type. Diffuse penetration of the compound into the cytoplasm was seen in one endothelial cell, but no fenestrations were detected. Junctions between the endothelial cells of vessels in rat spinal nerve roots are impermeable to lanthanum and most likely also to other large molecular substances like albumin. Thus, probable routes for serum albumin to enter the nerve roots, where it normally is present, must be either by centripetal extracellular diffusion from the ganglia and the peripheral nerve or by vascular leakage in the roots, caused by for instance pinocytosis across endothelial cells.

The possibility that serotonin can modify the early pathological sequences occurring in spinal cord trauma was investigated in a rat model. To that end we took advantage of the possibility of influencing serotonin pharmacologically by treating animals with a serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA) before the production of the injury and compared the results with injured, untreated controls. A unilateral incision was made into the dorsal horn of the lower thoracic cord (about 2.5 mm deep, 4.5 mm long) and the trauma. The injured region from untreated animals showed macroscopically at that time a pronounced swelling and the water content had increased by 3.5% as compared to intact controls. The segments rostral and caudal to the lesion also exhibited a profound increase in water content. Light microscopy revealed a significant expansion of the spinal cord as compared to controls. The swelling was most pronounced in the gray matter on the injured side. Electron microscopy showed distorted neurons, swollen astrocytes and extracellular edema in the gray matter in and around the primary lesion. There was also a sponginess in the surrounding white matter with disruption of myelin, collapsed axons and widened periaxonal spaces. Pretreatment of the rats with p-CPA significantly reduced the swelling of the injured spinal cord and there was no visible expansion. The ipsilateral edema in the central gray matter was considerable less pronounced as compared to that in untreated animals. The increase in water content was less than 1% in these animals. The neuronal and glial cell changes were also markedly reduced in the drugtreated rats. The disruption of myelin and the vacuolation of the gray matter were much less severe. Our results show that p-CPA can markedly modify the edema and the cellular changes occurring in the traumatic spinal injury and indicate that serotonin is somehow involved in the production of the early, and thus important, pathological events.

The possibility that serotonin can take part in the initiation of the increased microvascular permeability occurring in a spinal cord trauma was investigated in a rat model with 131I-sodium and lanthanum as tracers. We influenced the serotonin content in the tissue pharmacologically by treating animals with a serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA), before the production of the injury and compared the results with injured, untreated controls. A small incision was made in the dorsal horn of the lower thoracic cord. It caused a progressive extravasation of 131I-sodium in the damaged segment, measured after 1, 2 and 5 h. Rostral and caudal segments also showed a significant but lower accumulation of 131I-sodium. Lanthanum added to the fixative was used as an ionic tracer detectable by electron microscopy. The endothelial cells of microvessels removed from the perifocal region after 5 h showed a marked increase in the number of lanthanum-filled vesicles. Many endothelial cells had a diffuse penetration of the tracer into the cytoplasm and the basement membrane. However, the tight junctions usually remained closed to lanthanum. Pretreatment with p-CPA markedly reduced the extravasation of 131I-sodium measured at 5 h in the traumatized cord. At the cellular level, the endothelial vesicles filled with lanthanum approached the condition of uninjured animals. The diffuse infiltration of lanthanum into endothelial cells and its spread into the basement membrane of the vascular wall were usually absent. Our results indicate that serotonin plays a role in the initiation of the increased microvascular permeability which occurs in spinal cord injuries.

Passivation of psuedomorphic high electron mobility transistor (pHEMT) based MMIC's by silicon nitride films deposited by PECVD is reported here. These films were first optimized for passivation of MESFET's to get desired performance. No degradation in pHEMT/MESFET characteristics like Idss, gm Vp and Cgs were observed while only nominal degradation was found in Schottky diode ideality factor eta and its breakdown voltage VB. The refractive index of the films was 1.92 with 1200 A0 thickness. The films have high dielectric strength > 5E6 V/cm, low tensile stress < 5E9 dynes/cm2 and dielectric constant 6.9 -7.1. The etch rate of the film is ~ 900 A0/min in BHF and fine patterns can be etched with 1-2 minutes etch time in BHF. The film composition was analyzed by FTIR and SIMS studies.

The role of heme oxygenase (HO) in closed head injury (CHI) was examined using a potent HO and guanylyl cyclase inhibitor, zinc protoporphyrin (Zn-PP) in the rat. Blood-brain barrier (BBB) permeability to Evans blue and radioiodine, edema formation, and plasma and brain levels of serotonin were measured in control, CHI, and Zn-PP-treated CHI rats. CHI was produced by an impact of 0.224 N on the right parietal bone by dropping 114.6 g weight from a height of 20 cm in anesthetized rats. This concussive injury resulted in edema formation and brain swelling 5 hours after insult that was most pronounced in the contralateral hemisphere. The whole brain was edematous and remained in a semi-fluid state. Microvascular permeability disturbances to protein tracers were prominent in both cerebral hemispheres and the underlying cerebral structures. Plasma and brain serotonin showed pronounced increases and correlated with edema formation. Pretreatment with Zn-PP (10 mg/ kg, i.p) 30 minutes before or after CHI attenuated edema formation, brain swelling, plasma and brain serotonin levels, and microvascular permeability at 5 hours. Brain edema, BBB permeability, and serotonin levels were not attenuated when the compound was administered 60 minutes post-CHI suggesting that HO is involved in cellular and molecular mechanisms of edema formation and BBB breakdown early after CHI.

The role of histamine in edema formation, blood-spinal cord barrier (BSCB) permeability, and spinal cord blood flow (SCBF) following spinal cord injury (SCI) was examined using modulation of histamine H1, H2, and H3 receptors in the rat. Focal trauma to the spinal cord at the T10-11 level significantly increased spinal cord edema formation, BSCB permeability to protein tracers and SCBF reduction in the T9 and T12 segments. Pretreatment with histamine H1 receptor antagonist mepyramine (1 mg, 5 mg, and 10 mg/kg, i.p.) did not attenuate spinal pathophysiology following SCI. Blockade of histamine H2 receptors with cimetidine or ranitidine (1 mg, 5 mg, or 10 mg/kg 30 minutes before injury) significantly reduced early pathophysiological events in a dose dependent manner. The effects of ranitidine were far superior to cimetidine in identical doses. Pretreatment with a histamine H3 receptor agonist alpha-methylhistamine (1 mg and 2 mg/kg/i.p.), that inhibits histamine synthesis and release in the CNS, thwarted edema formation, BSCB breakdown, and SCBF disturbances after SCI. The lowest dose of histamine H3 agonist was most effective. Blockade of histamine H3 receptors with thioperamide (1 mg, 5 mg/kg, i.p.) exacerbated spinal cord pathology. These observations suggest that stimulation of histamine H3 receptors and blockade of histamine H2 receptors is neuroprotective in SCI.

The possibility that a chronic nerve ligation impairs the spinal cord cellular microenvironment was examined using leakage of endogenous albumin, reaction of astrocytes, and structural changes in a rat model. Rats subjected to 8 weeks of unilateral L4/L5 nerve ligation (a model of neuropathic pain) showed leakage of albumin, up-regulation of glial fibrillary acidic protein (GFAP) immunoreaction, and abnormal cell reaction. Distortion and loss of nerve cells as well as general sponginess of the gray matter was clearly evident. Cell changes were present in both dorsal and ventral horns and were most marked on the ipsilateral side compared to the contralateral cord. Nerve cell and glial cell changes are normally present in the regions showing intense albumin immunoreactivity, indicating disruption of the blood-spinal cord barrier (BSCB). Our observations indicate that a chronic nerve lesion has the capacity to induce selective breakdown of the BSCB that could be responsible for activation of astrocytes and abnormal cell reaction. These findings enhance our understanding of the pathophysiology of neuropathic pain and/or other spinal cord disorders.

Previous investigations from our laboratory show that up-regulation of neuronal nitric oxide synthase (NOS) following spinal cord injury (SCI) is injurious to the cord. Antiserum to dynorphin A (1-17) induces marked neuroprotection in our model of SCI, indicating an interaction between dynorphin and NOS regulation. The present investigation was undertaken to find out whether topical application of dynorphin A (1-17) antiserum has some influence on neuronal NOS up-regulation in the traumatized spinal cord. SCI was produced in anesthetized animals by making a unilateral incision into the right dorsal horn of the T10-11 segments. The antiserum to dynorphin A (1-17) was applied (1 : 20, 20 microL in 10 seconds) 5 minutes after trauma over the injured spinal cord and the rats were allowed to survive 5 hours after SCI. Topical application of dynorphin A (1-17) antiserum significantly attenuated neuronal NOS up-regulation in the adjacent T9 and T12 segments. In the antiserum-treated group, spinal cord edema and cell injury were also less marked. These observations provide new evidence that the opioid active peptide dynorphin A may be involved in the mechanisms underlying NOS regulation in the spinal cord after injury, and confirms our hypothesis that up-regulation of neuronal NOS is injurious to the cord.

We examined the potential efficacy of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) applied over traumatized spinal cord, alone or in combination, for attenuating motor dysfunction, blood-spinal cord barrier (BSCB) breakdown, edema formation, and cell injury in a rat model. Under Equithesin anesthesia, spinal cord injury (SCI) was performed by making a unilateral incision into the right dorsal horn of the T10-11 segment. The rats were allowed to survive 5 hours after trauma. The BDNF or GDNF was applied (0.1 to 1 microg/10 microl in phosphate buffer saline) 30, 60, or 90 minutes after SCI. Topical application of BDNF or GDNF 30 minutes after SCI in high concentration (0.5 microg and 1 microg) significantly improved motor function and reduced BSCB breakdown, edema formation, and cell injury at 5 hours. These beneficial effects of neurotrophins were markedly absent when administered separately either 60 or 90 minutes after injury. However, combined application of BDNF and GDNF at 60 or 90 minutes after SCI resulted in a significant reduction in motor dysfunction and spinal cord pathology. These novel observations suggest that neurotrophins in combination have potential therapeutic value for the treatment of SCI in clinical situations.

The neuroprotective efficacy of post-injury treatment with the antioxidant compound H-290/51 (10, 30, and 60 minutes after trauma) on immediate early gene expression (c-fos), blood-spinal cord barrier (BSCB) permeability, edema formation, and motor dysfunction was examined in a rat model of spinal cord injury (SCI). SCI was produced by a longitudinal incision into the right dorsal horn of the T10-11 segment under Equithesin anesthesia. Focal SCI in control rats resulted in profound up-regulation of c-fos expression, BSCB dysfunction, edema formation, and cell damage in the adjacent T9 and T12 segments at 5 hours. Pronounced motor dysfunction was present at this time as assessed using the Tarlov scale and the inclined plane test. Treatment with H-290/51 (50 mg/kg, p.o.) 10 and 30 minutes after SCI (but not after 60 minutes) markedly attenuated c-fos expression and motor dysfunction. In these groups, BSCB permeability, edema formation, and cell injuries were mildly but significantly reduced. These observations suggest that (i) antioxidants are capable of attenuating cellular and molecular events following trauma, and (ii) have the capacity to induce neuroprotection and improve motor function if administered during the early phase of SCI, a novel finding.

The possibility that the upregulation of hemeoxygenase (HO) enzyme responsible for carbon monoxide (CO) formation in the spinal cord following trauma is involved in edema formation and cell damage was examined in a rat model. A focal trauma to the rat spinal cord by making an incision into the right dorsal horn of the T10-11 segment resulted in profound upregulation of HO-2 (the constitutive isoform of the enzyme) expression in the T9 and T12 segments 5 h after injury. In these segments a marked increase in edema formation, nerve cell damage, and expression of heat shock protein (HSP 72) were observed. Pretreatment with p-chlorophenylalanine (p-CPA, a serotonin synthesis inhibitor) significantly attenuated the trauma induced edema formation, cell injury, and HSP expression. Upregulation of HO-2 in p-CPA treated traumatised rats was considerably reduced. These observations suggest that (i) spinal cord injury has the capacity to induce an upregulation of HO-2 and HSP expression, (ii) abnormal production of CO as reflected by HO-2 expression is injurious to the cord, and (iii) that endogenous serotonin is involved in HO-2 expression in the cord.

The influence of the potent L-type Ca[2+] channel antagonist Nimodipine on spinal cord evoked potentials (SCEP) and axonal injury following trauma to the spinal cord was examined in a rat model. Spinal cord injury (SCI) was produced by an incision into the right dorsal horn of the T10-11 segments under urethane anaesthesia (1.5 g/kg, i.p.). SCEPs were recorded by epidural electrodes placed over the T9 (rostral) and T12 (caudal) segments after stimulation of the right tibial and sural nerves. SCI induced a pronounced decrease of the SCEP negative amplitude in the rostral (T9) recordings immediately after trauma. Axonal injury seen as degradation of myelin basic protein (MBP) immunostaining and myelin vesiculation at the ultrastructural level was most pronounced at 5 h. Continuous administration of Nimodipine (2 microg/kg/min, i.v.) from 30 min prior to injury until sacrifice markedly attenuated the changes in SCEP amplitude and latency. Axonal damage, loss of MBP, and myelin vesiculation were much less evident in the nimodipine treated traumatised rats. These observations suggest that Ca[2+] channels play an important role in the trauma induced alterations in SCEP and axonal injury, and indicate a therapeutic value of Ca[2+] blockers in SCI.

The possibility that antiserum to tumour necrosis factor-alpha (TNF-alpha) is neuroprotective in spinal cord injury (SCI) was examined in a rat model. SCI was produced by making an incision into the right dorsal horn at the T10-11 segments. Top TNF-alpha antiserum at three concentrations (1:10; 1:50 and 1:100) given 30 min before or 2 min, 5 min or 10 min after trauma resulted in marked reduction in visible swelling, edema formation, and leakage of radiolabelled iodine tracer within the T9 and T12 segments at 5 h in a dose dependent manner. This neuroprotective effect was most pronounced when the antiserum at the highest dose level (1:10) was applied 10 min after SCI. The TNF-alpha antiserum also reduced the SCI induced upregulation of neuronal nitric oxide synthase (nNOS) immunoreactivity in a concentration dependent manner. Taken together, these results suggest that local application of TNF-alpha antiserum is neuroprotective in SCI and that this effect is mediated through NOS regulation.

The role of oxidative stress in spinal cord injury (SCI) induced upregulation of constitutive or inducible isoforms of nitric oxide synthase (cNOS or iNOS) is not well known. The present investigation was undertaken to examine the influence of an antioxidant compound H-290/51 (Astra-Zeneca, Mölndal, Sweden) on SCI induced cNOS and iNOS upregulation in a rat model. SCI induced by incision into the right dorsal horn of the T10-11 segment resulted in marked NOS upregulation. Upregulation of cNOS was most prominent in the uninjured T9 and T12 segments. On the other hand, iNOS expression was most marked in the injured T10-11 segments. These NOS immunoreactivities were mainly confined to the injured cells located in the edematous regions of the cord exhibiting profound leakage of Evans blue and [131]Iodine-sodium tracers. Pre-treatment with H-290/51 markedly attenuated the trauma-induced cNOS and iNOS expression along with the microvascular permeability disturbances, edema formation and cell injury. These results suggest that (i) oxidative stress is involved in SCI induced induction of cNOS and iNOS, (ii) NO plays an important role in the cord pathology, and (iii) that the compound H-290/51 has a potential therapeutic value in SCI.

The possibility that five new low molecular weight compounds with varying affinity and selectivity to the melanocortin receptors will exert neuroprotective effects in the spinal cord injury (SCI) induced edema formation and cell damage was examined in a rat model. A focal trauma of the rat spinal cord made by an incision into the right dorsal horn (T10-11) resulted in profound edema formation, leakage of Evans blue albumin and cell injury of the T9 segment at 5 h. Topical application of the Melacure compound ME10501 in high doses (10 microg in 10 microl) given 5 min after SCI resulted in most significant neuroprotection of the T9 segment of the cord compared to other compounds. Thus, marked reduction in water content, leakage of Evans blue albumin, and cell injury were observed in ME10501 treated traumatised rats. These observations suggest that the non-peptide compound ME10501 with affinity to the melanocortin receptor MC4 is capable to induce neuroprotection in the spinal cord following trauma not reported earlier.