3,416 research outputs found
No evidence for oncogenic mutations in guanine nucleotide-binding proteins of human adrenocortical neoplasms
No full textG-Proteins are membrane-bound heterotrimeric polypeptides that couple receptor signals to second messenger systems such as cAMP. Recently, point mutations at 2 codons of the highly preserved alpha-chain of Gs, the adenyl cyclase-stimulating G-protein, were found in GH-secreting pituitary tumors. These mutations resulted in constitutively activated Gs alpha and high intracellular cAMP levels. In addition, point mutations at similar codons of a different G-protein, G(i) alpha 2, were reported in adrenocortical neoplasms, suggesting a potential role of this isoform in the genesis of these tumors. We reevaluated the frequency of constitutively activating point mutations in the alpha- chain of the stimulatory (Gs alpha) and inhibitory (G(i) alpha 2) G- proteins in human adrenocortical tumors. Seven adrenocortical carcinomas, 2 human adrenocortical tumor cell lines, and 11 adrenocortical adenomas were studied. Genomic DNA was purified from either frozen tumor tissue or paraffin-embedded sections. Using specific primers and the polymerase chain reaction, DNA fragments surrounding codons 201 and 227 (Gs alpha) and 179 and 205 (G(i) alpha 2) were amplified and visualized on a 2% agarose gel. In a second asymmetric polymerase chain reaction, using nested primers, single stranded DNA was generated using 1-10 microL of the initial amplification mixture and directly sequenced using the dideoxy chain termination method of Sanger. We found no mutations at codons 201, 227 and 179, 205 of Gs alpha and G(i) alpha 2, respectively, in the tumors studied. We conclude that previously identified oncogenic point mutations in the stimulatory and inhibitory alpha-chain of G-proteins do not appear to be present at high frequency in adrenal neoplasms. Thus, the mechanism(s) of tumorigenesis in these tumors is different from that in GH-secreting adenomas and may involve oncogenic mutations of other cell constituents
Further evidence supporting a role for gs signal transduction in severe malaria pathogenesis.
No full textWith the functional demonstration of a role in erythrocyte invasion by Plasmodium falciparum parasites, implications in the aetiology of common conditions that prevail in individuals of African origin, and a wealth of pharmacological knowledge, the stimulatory G protein (Gs) signal transduction pathway presents an exciting target for anti-malarial drug intervention. Having previously demonstrated a role for the G-alpha-s gene, GNAS, in severe malaria disease, we sought to identify other important components of the Gs pathway. Using meta-analysis across case-control and family trio (affected child and parental controls) studies of severe malaria from The Gambia and Malawi, we sought evidence of association in six Gs pathway candidate genes: adenosine receptor 2A (ADORA2A) and 2B (ADORA2B), beta-adrenergic receptor kinase 1 (ADRBK1), adenylyl cyclase 9 (ADCY9), G protein beta subunit 3 (GNB3), and regulator of G protein signalling 2 (RGS2). Our study amassed a total of 2278 cases and 2364 controls. Allele-based models of association were investigated in all genes, and genotype and haplotype-based models were investigated where significant allelic associations were identified. Although no significant associations were observed in the other genes, several were identified in ADORA2A. The most significant association was observed at the rs9624472 locus, where the G allele (approximately 20% frequency) appeared to confer enhanced risk to severe malaria [OR = 1.22 (1.09-1.37); P = 0.001]. Further investigation of the ADORA2A gene region is required to validate the associations identified here, and to identify and functionally characterize the responsible causal variant(s). Our results provide further evidence supporting a role of the Gs signal transduction pathway in the regulation of severe malaria, and request further exploration of this pathway in future studies
Epidemiology, management and outcome of gastroschisis in Sub-Saharan Africa: Results of an international survey
No full textBackground: The aim was to compare gastroschisis (GS) epidemiology, management and outcome in low-income countries (LIC) in Sub-Saharan Africa (SSA) with middle- (MIC) and high-income countries (HIC). Materials and Methods: A 10-question survey was administered at the 2012 Pan-African Paediatric Surgery Association Congress. Results are presented as median (range); differences were analysed using contingency tests. Results: A total of 82 delegates (28 countries [66 institutions]) were divided into LIC (n = 11), MIC (n = 6) and HIC (n = 11). In LIC, there were fewer surgeons and more patients. LIC reported 22 cases (1-184) GS/institution/year, compared to 12 cases (3-23)/institution/year in MICs and 15 cases (1-100)/institution/year in HICs. Antenatal screening was less readily available in LIC. Access to parenteral nutrition and neonatal intensive care in LIC was 36% and 19%, compared to 100% in HIC. Primary closure rates were similar in LIC and HIC at 58% and 54%, respectively; however, the majority of staged closure utilised custom silos in LIC and preformed silos in HIC. In LIC, mortality was reported as >75% by 61% delegates and 50-75% by 33%, compared to <25% by 100% of HIC delegates (P < 0.0001). Conclusions: Gastroschisis is a problem encountered by surgeons in SSA. Mortality is high and resources in many centres inadequate. We propose the implementation of a combined epidemiological research, service delivery training and resource provision programme to help improve our understanding of GS in SSA whilst attempting to improve outcome
EBUS-GS and VBN for GGO lesions
No full textBackground: Endobronchial ultrasonography with guide sheath (EBUS-GS) could be useful for diagnosing ground-glass opacity (GGO) predominant-type lesions in the peripheral lung. Furthermore, several studies have reported that transbronchial biopsy using EBUS-GS and virtual bronchoscopic navigation (VBN) was safe and effective for diagnosing small peripheral lung lesions. Our objectives were to diagnose solitary peripheral GGO predominant-type lesions by transbronchial biopsy using EBUS-GS and VBN under radiographic fluoroscopic guidance, and to evaluate the clinical factors associated with diagnostic yield. Methods: The medical records of 169 patients with GGO predominant-type lesions who underwent transbronchial biopsy using EBUS-GS and VBN under radiographic fluoroscopic guidance were retrospectively reviewed. Results: Endobronchial ultrasonography images could be obtained for 156 (92%) of 169 GGO predominant-type lesions, and 116 (69%) were successfully diagnosed by this method (20 of 31 pure GGO lesions [65%]; 96 of 138 mixed GGO predominant-type lesions [70%]). The mean size of diagnosed lesions was significantly larger than that of nondiagnosed lesions (22 mm versus 18 mm, p < 0.01). Regarding diagnostic yield based on computed tomography sign, cases with presence of a bronchus leading directly to a lesion had significantly higher diagnostic yield than the other lesions (p < 0.01). Conclusions: The addition of VBN to EBUS-GS could be useful in clinical practice for diagnosing GGO predominant-type lesions in the peripheral lung
A colour-centre model for second-order optical nonlinearities in germanosilicate optical fibres
No full textSecond-order nonlinearities can be induced in germanosilicate (GS) glass fibers in a variety of ways: by coherent superposition of pump and second-harmonic light (a third-order dc polarization Pdc is induced that breaks the inversion symmetry); by excitation poling with blue light and an external dc field, Epol ; and by strong Epols 's in the absence of light. There is as yet no satisfactory agreement over the nature of the underlying alignment process. From related detailed studies of color-center behavior in GS fiber, we have formulated a self-consistent model as developed in the following points. &more..
Rigorous results on the strongly correlated electron systems by the spin-reflection-positivity method
No full textIn this talk, we shall briefly review some results on the strongly correlated electron systems, derived recently by applying Lieb's spin-reflection-positivity method. To explain the basic ideas of this method to a wide audience, we emphasize the important role played by Marshall's rule in studying the many-body systems.Physics, AppliedPhysics, Condensed MatterPhysics, MathematicalSCI(E)CPCI-S(ISTP)
Layout Implementation of A 10-Bit 1.2 GS/s Digital-to-Analog Converter In 90nm CMOS
No full textDigital-to-analog converters are the interface circuits between digital and analog domains. They are used in data communication applications and different sorts of applications where transformation amongst digital and analog signals is needed. High-speed data converters are needed to match the bandwidth demands of the present-day communication systems. This thesis presents the layout implementation of a 10-bit current steering DAC with a sampling rate of about 1.2 GS/s using CMOS 90 nm technology. Current steering DAC topology is used in high-speed applications. The DAC in this thesis is designed using a segmented architecture in which 4 LSB current cells are binary weighted and 6 MSB current cells are thermometer encoded. The issues with the mixed signal layout were discussed. The schematic design does not consider the effect of parasitic resistance and capacitance whereas the layout does. The performance of the schematic and layout designs of the sub-circuits was compared. Post layout simulations of the implemented current steering DAC were performed in Cadence with 1.2 GHz clock and 55.07 MHz input signal. The simulations show that the DAC is functional and comparisons between the layout and schematic were presented
Antiferromagnetic correlation in the half-filled strongly correlated electron models at nonzero temperature: A rigorous result
No full textAs an extension of our previous rigorous investigation on the spin correlations in the ground states of the half-filled Hubbard model and the periodic Anderson model [G. S. Tian, Phys. Rev. B 50, 6246 (1994)], in the present paper we study the behavior of these correlation functions at finite temperature. We show rigorously that, at any T not equal0, the predominant spin correlations in these systems are antiferromagnetic. Furthermore, based on this result, we also show that a quasi-one (or two)-dimensional itinerant electron ferrimagnet must have a gapless branch of ferromagnetic excitations. This conclusion is consistent with the previous results derived by the spin-wave theory.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000169283000058&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Physics, Condensed MatterSCI(E)10ARTICLE22null6
Regulation of glutamine synthetase in rainbow trout, Oncorhynchus Mykiss
No full textPrevious experiments have shown that chronically elevated external ammonia exposure in rainbow trout results in an increase in plasma cortisol levels as well as in brain glutamine synthetase (GS) activity. I hypothesized that the stimulation of GS activity is due to elevated cortisol. Rainbow trout were fed either a control diet or diets enriched in 100 or 200 [mu]g cortisol/g food for 3 and 6 days. Brain, liver, red and white muscle GS activities were not affected by elevated cortisol at either time point. To determine if cortisol must interact with factors present only during high ammonia exposure in order to stimulate GS activity, fish were treated with metyrapone (which inhibits cortisol synthesis) and then exposed to NH4Cl for 24 hours. Relative to untreated control fish, sublethal high NH4Cl exposure did not affect brain, liver, red and white muscle GS activities. Additionally, fish with partially blocked cortisol synthesis had GS activities similar to sham control fish. Ultimately, the present study demonstrates that cortisol does not have a direct affect on GS activity in rainbow trout. In addition, it demonstrates that basal levels of GS activity, with possibly other mechanisms for ammonia detoxification, are sufficient to cope with sublethal high ammonia exposure
A 1-GS/s 6–8-b Cryo-CMOS SAR ADC for Quantum Computing
No full textThis article presents a two-times interleaved, loop-unrolled SAR analog-to-digital converter (ADC) operational from 300 down to 4.2 K. The 6-8-bit resolution and the sampling speed up to 1 GS/s are targeted at digitizing the multi-channel frequency-multiplexed input in a spin-qubit reflectometry readout for quantum computing. To optimize the circuit for the altered device behavior at cryogenic temperatures, a modified common-mode switching scheme is adopted as well as a flexible calibration. The design is implemented in 40-nm CMOS technology and achieves 36.2-dB signal to noise and distortion ratio (SNDR) for Nyquist input at 4.2 K while maintaining a Walden figure of merit (FOM textsubscript W) of 200 pJ/conv-step (for a 10.8-mW power consumption), including the clock receiver, and 15 pJ/conv-step (for a 0.8-mW power consumption) for just the core ADC. With these specifications, the ADC can support the simultaneous readout of 20 qubit channels with a power consumption of 0.5 mW/qubit, thus advancing toward the full integration of the cryogenic readout for future large-scale quantum processors.QCD/Sebastiano LabElectronicsQuantum Circuit Architectures and Technolog
- …
