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The innate immune receptor Mincle senses lipid-based molecules derived from pathogens, commensals and altered self. Based on emerging structure-activity relationships we design simple alkyl 6-O-acyl-b-D-glucosides that are effective agonists of Mincle and signal with potency on par with the prototypical ligand trehalose dimycolate.

The fidelity of acylation regioselectivity in the synthesis of mixed glycosyl diacylglycerols can be accurately measured by quantitative 13C NMR spectroscopy using a 1-13C-labelled fatty acid and a paramagnetic relaxation enhancement agent. Exquisite regioselectivity is achieved using a stepwise acylation/substitution of a glycosyl β-bromohydrin, which is applied to the total synthesis of Streptococcus pneumoniae Glc-DAG-s2.

N-Phenyltrifluoroacetimidoyl chloride (PTFAI-Cl) is a reagent widely used for the preparation of glycosyl N-phenyltrifluoroacetimidates. However, the most commonly applied method requires carbon tetrachloride, a hepatotoxic reagent that has been phased out under the Montreal Protocol. We report a new synthesis of N-phenyltrifluoroacetimidoyl chloride (PTFAI-Cl) using dichlorotriphenylphosphane and triethylamine.

Geiger-mode avalanche photodiodes (GM-APDs) grown by organometallic vapor phase epitaxy are of interest for several low-light-level applications, including laser radars and single-photon-counting optical communications. Materials systems based on GaInAsP lattice matched to InP are critical to the performance of GM-APDs at both 1.06- and 1.55 - μ m wavelengths. Growth temperature, growth rate, and V/III ratio were investigated to determine the effect each had on important device parameters, dark count rate and after-pulsing. Improvements of growth conditions led to a 44% reduction in dark count rate (DCR), but after-pulsing behavior, and thus dead time of GM-APDs was unaffected. The improvement of growth conditions has led to devices with DCRs at 300 K of 8 × 10 9 Hz / cm 2 with dead times still at approximately 1 μ s .

Chemical hydrides, such as sodium borohydride ( NaBH 4 ) , offer promising gravimetric and volumetric hydrogen storage densities. The overall system energy density depends on the reactor performance. In this study, a novel intergrated reactor design in which catalyst bed is integrated with a heat exchanger for autothermal operation showed significant improvements in reactor performance. Over 200% enhancement in reactor throughput was achieved with the integrated reactor at 99% fuel conversion with constant reaction temperature profiles over a wide range of fuel flow rates. Impacts of improved performance on system operation and overall energy density of chemical hydride based hydrogen storage system were also discussed.

Arrays of InP-based avalanche photodiodes (APDs) with InGaAsP absorber regions have been fabricated and characterized in the Geiger mode for photon-counting applications. Measurements of APDs with InGaAsP absorbers optimized for 1.06 mum wavelength show dark count rates (DCRs)

Catalytic hydrolysis of sodium borohydride is a promising technology for hydrogen storage. In this study, we report the performance of Millennium Cell Hydrogen on Demand TM ( HOD TM ) hydrogen storage system using a supported catalyst. Dynamic reactor startup and response characteristics were measured using a fixed-bed catalyst reactor at various hydrogen demand conditions. The catalyst reactor was operated without need of fuel preheating. Catalyst durability of more than 700 h was demonstrated with a sodium borohydride conversion over 95% at a liquid feed hourly space velocity (LHSV) of about 15 h - 1 and under a system pressure of 483 kPa.

Airborne imaging spectrometers can record spatially-explicit information on the absorption features associated with foliar biochemicals in a forest canopy. The spectra of a single species pine canopy were recorded by the National Aeronautics and Space Administration's (NASA) Airborne Visible/Infrared Imaging Spectrometer (AVIRIS). Up to three wavebands were correlated to the concentration of chlorophyll, nitrogen, lignin, and cellulose (R/sup 2/=0.96,0.94,0.93, and 0.61, respectively) and the content of these four biochemicals (R/sup 2/=0.98,0.91,0.88, and 0.92, respectively). The AVIRIS data were used, for the first time, to map the content of these biochemicals within the forest canopy and the accuracy was between 3-7% of the mean.

Three physical field models were constructed to assess the effects on soil of a chromated fluoride wood preservative treatment used at the groundline of creosoted electricity distribution poles. One model contained an untreated aged creosoted pole section in sandy loam soil, the second contained a remedially treated aged creosoted pole section in sandy loam soil and the third a similarly treated section in sand-amended sandy loam soil. The models were subjected to the equivalent of 6 months simulated rainfall exposure, and soil samples recovered from each model soilbed were used for the determination of soil dehydrogenase activity, fluoride and total chromium concentrations. Soil dehydrogenase activity was measured on both rye meal-supplemented and unsupplemented soil samples. Irrespective of supplementation, significant reductions in dehydrogenase activity were associated with increased soil concentrations of leached preservative constituents which were found within 5 cm of the treated pole sections. These reductions were enhanced by the lower organic matter content of the sand-amended soil. Supplementation with rye meal resulted in raised levels of dehydrogenase activity in all soil samples, which highlighted the negative effects of preservative soil contamination on microbial activity.

The optical properties of strained-layer InGaAs-GaAs-AlGaAs quantum-well lasers with a cavity comprised of a single cleaved facet and a dry etched corner reflector (CR) is described. For comparison, these data are contrasted with data for Fabry-Perot lasers made from the same material and having either two cleaved facets or one cleaved and one straight-etched facet. The etched CR exhibits higher overall reflectivity than the straight-etched and cleaved facet structures, resulting in lower threshold current density and higher efficiency. However, near-field measurements indicate that improvement in reflectivity from the etched CRs is offset by their tendency to favor off-order transverse modes. >

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InGaAs-GaAs-AlGaAs strained-layer distributed-feedback (DFB) ridge-waveguide lasers requiring a single metalorganic chemical vapor deposition (MOCVD) growth step are shown to operate in a single longitudinal mode up to 2.2*I/sub th/ with an antireflection (AR) coating applied to one facet under room temperature, pulsed conditions. A value of kL=0.33 has been determined from threshold gain calculations for coated and uncoated devices. Weak lateral optical confinement, provided by unpumped lateral gratings is demonstrated by the absence of antiguiding effects, and a real lateral index step of approximately 4*10/sup -3/ is determined from near-field emission patterns. >

The fabrication of reliable InP-based Geiger- mode avalanche photodiodes are described. Devices passivated with polyimide coated with silicon nitride have not degraded even while aging under more strenuous conditions than those used in fielded systems.

Design modifications to InP-based Geiger-mode avalanche photodiodes are described that improve reliability. Geiger-mode aging at multiple conditions can cause significant degradation in some design variants while linear mode (below breakdown) aging does not.

Summary form only given. Recently, lasers with monolithically integrated external modulators fabricated using selective-area epitaxy in the InGaAs-InGaAsP material system have received much attention for applications in long distance fiber communication. As of yet little work has been done on lasers with monolithically integrated modulators in the InGaAs-GaAs material system. Applications for lasers with monolithically integrated external-cavity modulators in the InGaAs-GaAs material system include wavelength-division multiplexing (WDM) local area networks and differential absorption LIDAR systems, for both of which low chirp is desired. We present a multiple quantum well (MQW) wavelength-tunable distributed Bragg reflector (DBR) laser with monolithically integrated external-cavity electroabsorption (EA) modulator.

Asymmetric cladding InGaAs-GaAs ridge waveguide distributed Bragg reflector (RW-DBR) lasers are demonstrated with a spectral linewidth as low as 39 kHz for an output power of 24 mW. The fabrication requires only a single standard epitaxial growth of a laser structure while the use of a thin top cladding layer allows for a shallow reactive ion etch of the distributed Bragg reflector. These RW-DBR lasers have a threshold current of 12.4 mA, a slope of 0.3 W/A, and over 40 dB side-mode suppression at a wavelength of 1010 nm.

The design and operation of strained-layer InGaAs-GaAs lasers with monolithically integrated intracavity electroabsorption modulators fabricated by selective-area epitaxy are presented. Devices with modulator lengths of 290, 620, and 1020 /spl mu/m have cw threshold currents of 9, 7.5, and 7.5 mA, respectively, at a modulator bias of 0 V. These devices also exhibit extinction ratios of 16.5, 19.5, and 20.5 dB, respectively, at a modulator bias of 2 V.

Ridge waveguide lasers with a thin upper cladding layer are fabricated with a two-step selective-area MOCVD growth. The lower cladding, active region, and upper cladding are all grown in the initial MOCVD growth. A second growth over an oxide pattern is used to define the ridge with 0.15 /spl mu/m of GaAs, which serves as both the contact and index increasing layer. Ridge lasers fabricated by this method (3/spl times/425 /spl mu/m) have a cw threshold current of 12.6 mA, slope efficiency of 0.26 W/A, and operate in a fundamental transverse mode as well as stable fundamental lateral mode to 20 times threshold. >

An InGaAs-GaAs-AlGaAs strained layer single quantum laser array with a reactive ion etched corner reflector array as its rear facet has been fabricated. The corner reflectors play a two-fold role as a highly reflective rear mirror and as a phase-locking coupler. Phase locked operation with beam widths as low as 0.64/spl deg/ are obtained at pumping currents up to 4/spl times/I/sub th/ and output powers up to 60 mW. The coupling mechanism and the benefit of the corner reflector to output performance are discussed. >

Strained-layer InGaAs-GaAs-AlGaAs single quantum well buried heterostructure lasers grown by selective-area MOCVD are described. Threshold currents of 2.65 mA for an uncoated device and 0.97 mA for a coated device have been obtained. A peak optical output power of 170 mW per uncoated facet for a device with a 4 /spl mu/m active region width was also achieved. Peak emissions wavelengths range from 0.956 to 1.032 /spl mu/m. >

The uniqueness of the nitrides for detectors lies in their wide bandgaps that can be tailored by varying the composition of the quaternary alloy AlInGaN. We report on the performance of GaN PIN photodiodes grown by MOVPE with various intrinsic region thicknesses.

Ti-Au and annealed Ti-Pt-Au p-type contacts are demonstrated to improve the adhesion over a pure gold contact and allow annealing of the metallization to thin p-cladding laser structures at the expense of an increase in the optical loss. As little as 10 angstroms of titanium is adequate for an adhesion layer and only increases the optical loss by 1.6 cm-1 over a pure gold metallization which has an optical loss of 10.0 cm-1. A metallization of 15 angstroms Ti - 15 angstroms Pt - 1500 angstroms Au is adequate for an anneal at 410 degree(s)C for 10 sec and increases the optical loss by 7.0 cm-1.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Using a chick P2Y1 receptor cDNA probe we have isolated a mammalian P2Y receptor clone from a bovine aortic endothelial cell Library. The sequence has a high degree of similarity to the chick P2Y1 clone. When transfected into the Jurkat cell line, the cDNA conferred sensitivity to purinoceptor agonists. Using fura-2 loaded cells the potency order at the receptor was found to be 2-methlythioadenosine 5′ triphosphate = adenosine 5′ diphosphate > adenosine 5′ triphosphate >> α,β-methyleneadenosine 5′ triphosphate and uridine 5′ triphosphate. This corresponds to the agonist potency order expected for the bovine aortic endothelial cell P2Y receptor.

1 The effects of indomethacin, dazoxiben and EPO45 on collagen-induced platelet aggregation in vivo were studied in guinea-pigs and rats to determine the involvement of the prostaglandin endoperoxide/thromboxane A2 pathway in the aggregatory response. 2 Indomethacin and EPO45 (a thromboxane receptor antagonist) partially inhibited platelet aggregation in rats. It was concluded that only one third of the aggregatory response to collagen was mediated by the products of cyclo-oxygenase conversion of arachidonic acid. 3 In rats, dazoxiben was inactive although the conversion of the prostaglandin endoperoxides to thromboxane A2 was inhibited (measured as thromboxane B2). 6-keto PGF1α was detected in plasma after collagen was injected into dazoxiben-treated rats. In this species therefore, the endoperoxides have significant aggregatory activity whilst the apparent increase in the level of prostacyclin was not sufficient to have any anti-aggregatory effect. 4 All three drugs were active in the guinea-pig. About 60% of the aggregatory response to collagen was due to the products of the cyclo-oxygenase pathway, the main mediator being thromboxane A2. 5 In guinea-pigs, dazoxiben also elevated 6-keto PGF1α in the plasma after an injection of collagen. However, this apparent increase in prostacyclin production did not contribute to the anti-aggregatory effect.

Using the Technicon Autocounter, the mechanisms involved in collagen-induced platelet aggregation in vivo have been studied without the interference of an anticoagulant. Extracellular divalent cation was essential for in vivo platelet aggregation. Non-steroidal anti-inflammatory drugs completely inhibited the aggregation induced by collagen in platelet-rich plasma in in vitro or ex vivo studies. In vivo only a maximum of 50% inhibition was achieved when release of thromboxane A2 (TXA2) was completely inhibited. Therefore in vivo, collagen causes aggregation through more than one pathway which operate independently of each other and which are all dependent on extracellular divalent cation. In vivo, when different doses of collagen were compared, aggregation produced by low doses of collagen was more dependent upon prostaglandin endoperoxide/TXA2 formation.

1 A fungal extract which produces a cutaneous hypersensitivity reaction in the plaice, Pleuronectes platessa L., was incubated in vitro with the skin of this teleost fish. Samples of incubation media were assayed for smooth muscle stimulating activity. 2 Prostaglandin E2 was identified by bioassay, thin-layer chromatography, ultraviolet absorption spectroscopy and gas chromatography--mass spectrometry. Release from challenged skin was maximum after 60 min incubation. 3 Analysis of the fatty acid composition of plaice skin showed that although arachidonic acid was present (3% of total fatty acids), the precursor of prostaglandin E3, eicosapentaenoic acid contributed 9% of total. 4 Indomethacin (50 mg/kg i.p) did not inhibit the erythema induced by the fungal extract, whilst a dose of 1 mg/kg maximally inhibited prostaglandin release from skin on incubation in vitro. 5 It is concluded that prostaglandins do not have an exclusive role in the mediation of the hypersensitivity reaction.

1. 1. Arachidonic acid (AA) and eicosapentaenoic acid (EPA), the precursors of prostaglandin E 2 (PGE 2 ) and PGE 3 , represent 3 and 9% respectively of the total fatty acids isolated from plaice skin. 2. 2. A microsomal preparation from plaice skin converted 2% of AA, but only 0.3% of EPA. 3. 3. Microsomal PG synthetase activity was completely inhibited by indomethacin (1 mM) whereas hydrocortisone (10 mM) was inactive. 4. 4. EPA caused a concentration-dependent inhibition of PGE 2 synthesis from AA and could therefore influence the inflammatory response resulting from the release of PGE 2 in plaice skin.

The effects of BW755C, benoxaprofen, indomethacin and piroxicam were studied on intravascular platelet aggregation using continuous platelet counting. Plasma levels of thromboxane B2 (TxB2) and 6-keto prostaglandin F1 (6-keto PGF1 alpha) were measured by radioimmunoassay. BW755C, a dual inhibitor of arachidonic acid metabolism, potentiated or inhibited aggregation depending on dose. BW755C increased TxB2 and 6-keto PGF1 alpha plasma levels at low doses. At higher doses BW755C inhibited aggregation and reduced TxB2 plasma levels. At 16 mg/kg BW755C, 6-keto PGF1 alpha was detected. Benoxaprofen also potentiated collagen-induced aggregation. 8 mg/kg indomethacin was shown to have a short lasting increased inhibitory action on collagen-induced aggregation when compared with the more specific cyclooxygenase inhibitor, piroxicam. 6-keto PGF1 alpha was detected in plasma from rats treated with indomethacin and piroxicam. The results obtained using low doses of BW755C suggest that the lipoxygenase pathway is involved in platelet aggregation. Interpretation of the results obtained using higher doses of drugs also suggests this involvement though some nonspecific actions of the drugs must be taken into consideration. Further work is required to detail the role of lipoxygenase products in collagen-induced intravascular platelet aggregation.

Intravascular platelet aggregation has been studied by measuring the response to aggregating agents using continuous platelet counting. Dose-dependent falls in platelet count occurred after the injection of collagen, prostaglandin H2 (PGH2), arachidonic acid (AA) and four synthetic prostanoids in rats. Indomethacin partially inhibited collagen- and AA-induced aggregation in the rat and collagen-induced aggregation in the rabbit. Indomethacin and aspirin did not produce a dose-dependent inhibition of collagen-induced aggregation over the range of doses tested. 1-n-butylimidazole inhibited collagen- and PGH2-induced aggregation in the rabbit but did not inhibit collagen- or AA-induced aggregation in the rat.

Two synthetic thromboxane A 2 agonists were compared on two isolated smooth muslce preparations, the rat aorta and stomach-strip using a superfusion cascade. 11.9 epoxymethano-PGH 2 contracted both preparations in a concentration dependent manner. Cumulative concentration-response curves showed that azo PGH 2 was twice as active as 11.9 epoxymethano PGH 2 on the aorta and nearly four times as active as 11.9 epoxymethano PGH 2 on the stomach-strip. Statistical analysis of the agonist concentration-response curves showed a significant differences when responses to azo PGH 2 were compared on the two preparations and when responses to azo PGH 2 and 11.9 epoxymethano PGH 2 were compared to the aorta preparation. When EP045, a thromboxane receptor antagonist was used the PA 2 values obtained were not significantly different using the two agonists on the two preparations. The pA 2 values indicate that both agonists act on the same receptor but the comparison of the concentration-response curves suggest that azo PGH 2 may be acting at another receptor as well as the thromboxane receptor in the stomach-strip.

SummaryThe mechanism of collagen-induced sudden death in rabbits was studied by measuring blood pressure (BP), heart rate, ECG, the continuous platelet count and the plasma levels of thromboxane B2 (TxB2) and 6-keto prostaglandin Fia (6-keto PGF1α). Death was preceded by myocardial ischaemia and a sharp fall in BP which occurred before any fall in platelet count was observed. The calcium entry blockers (CEBs), verapamil, nifedipine and PY 108-068 protected the rabbits from sudden death without any significant effect on the decrease in the platelet count or increase in plasma TxB2 levels. 6-keto PGF1α could not be detected in any plasma samples. Indomethacin and tri-sodium citrate also protected the rabbits but significantly reduced the fall in platelet count and plasma TxB2. In vitro studies on isolated aortae indicated that verapamil non-specifically inhibited vasoconstriction induced by KC1, adrenaline and U46619 (a thromboxane agonist). It is concluded that CEBs physiologically antagonize the vasoconstricting actions of platelet-derived substances and that it is coronary vasoconstriction that is primarily the cause of death.