511 research outputs found
Quantum Oscillations of Photocurrents in HgTe Quantum Wells with Dirac and Parabolic Dispersions
We report on the observation of magneto-oscillations of terahertz radiation
induced photocurrent in HgTe/HgCdTe quantum wells (QWs) of different widths,
which are characterized by a Dirac-like, inverted and normal parabolic band
structure. The photocurrent data are accompanied by measurements of
photoresistance (photoconductivity), radiation transmission, as well as
magneto-transport. We develop a microscopic model of a cyclotron-resonance
assisted photogalvanic effect, which describes main experimental findings. We
demonstrate that the quantum oscillations of the photocurrent are caused by the
crossing of Fermi level by Landau levels resulting in the oscillations of spin
polarization and electron mobilities in spin subbands. Theory explains a
photocurrent direction reversal with the variation of magnetic field observed
in experiment. We describe the photoconductivity oscillations related with the
thermal suppression of the Shubnikov-de Haas effect.Comment: 16 pages, 13 figure
The Origin of Primitive Cells, Nutrient Intake, and Non-Enzymatic Elongation of Encapsulated Nucleotides
Fatty acids and fatty alcohols are commonly found in experiments simulating the prebiotic 'soup'. These amphiphiles can be synthesized under prebiotic conditions, at least as long as the molecules are chemically relatively simple and do not need to be enantiomerically pure. In the context of topical origin-of-life theories, two distinct formation pathways for amphiphiles have been described; one related to geophysical sites, such as marine hydrothermal systems, and another to extraterrestrial sources, such as the proto-solar nebula, which was fed by interplanetary and interstellar nebulae. The chemical analysis of each provides individual characteristic challenges
The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia
© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Despite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV+) interneurons in schizophrenia, their functional consequences remain elusive. Since PV+ interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV+ interneurons is still unclear. Here we used a computational model of auditory steady-state response (ASSR) deficits in schizophrenia. We investigated the differential effects of decelerated synaptic dynamics, caused by subcellular alterations at two subtypes of PV+ interneurons: basket cells and chandelier cells. Our simulations suggest that subcellular alterations at basket cell synapses rather than chandelier cell synapses are the main contributor to these deficits. Particularly, basket cells might serve as target for innovative therapeutic interventions aiming at reversing the oscillatory deficits.Peer reviewe
STRUCTURE OF METHYLPHEOPHORBIDE-RCI
he methanolic extract of the cyanobacterium (blue-green alga) Spirulina geitleri has been treated with methanolic acid to convert all chlorophyllous pigments to their methylpheophorbides. Fractionation of the latter from methylpheophorbide a by thin layer chromatography and high pressure liquid chromatography yielded methylpheophorbide-RCI. Its structure has been determined as 132S-hydroxy-20-chloro-methylpheophorbide a by 1H-nuclear magnetic resonance, absorption and circular dichroism spectroscopy, mass spectrometry and by partial synthesis from chlorophyll a. The pigment is isolated from Spirulina geitleri irrespective of the use or omission of chlorinated substances during the isolation procedure
Article Real-Time Monitoring of Protein Complexes Reveals their Quaternary Organization and Dynamics
SUMMARY The dynamics of protein complexes are crucial for their function yet are challenging to study. Here, we present a nanoelectrospray (nESI) mass spectrometry (MS) approach capable of simultaneously providing structural and dynamical information for protein complexes. We investigate the properties of two small heat shock proteins (sHSPs) and find that these proteins exist as dodecamers composed of dimeric building blocks. Moreover, we show that these proteins exchange dimers on the timescale of minutes, with the rate of exchange being strongly temperature dependent. Because these proteins are expressed in the same cellular compartment, we anticipate that this dynamical behavior is crucial to their function in vivo. Furthermore, we propose that the approach used here is applicable to a range of nonequilibrium systems and is capable of providing both structural and dynamical information necessary for functional genomics
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Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial
Peginterferon plus ribavirin achieves sustained virological response (SVR) in fewer than half of patients with genotype 1 chronic hepatitis C virus infection treated for 48 weeks. We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b and ribavirin.
In part 1 of this trial, undertaken in 67 sites in the USA, Canada, and Europe, 520 treatment-naive patients with genotype 1 hepatitis C virus infection were randomly assigned to receive peginterferon alfa-2b 1·5 μg/kg plus ribavirin 800–1400 mg daily for 48 weeks (PR48; n=104); peginterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PRB24; n=103) or 44 weeks (PR4/PRB44; n=103); or peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 28 weeks (PRB28; n=107) or 48 weeks (PRB48; n=103). In part 2, 75 patients were randomly assigned to receive either PRB48 (n=16) or low-dose ribavirin (400–1000 mg) plus peginterferon alfa-2b and boceprevir three times a day for 48 weeks (low-dose PRB48; n=59). Randomisation was by computer-generated code, and study personnel and patients were not masked to group assignment. The primary endpoint was SVR 24 weeks after treatment. Analysis was by intention to treat. This study is registered with
ClinicalTrials.gov, number
NCT00423670.
Patients in all four boceprevir groups had higher rates of SVR than did the control group (58/107 [54%, 95% CI 44–64], p=0·013 for PRB28; 58/103 [56%, 44–66], p=0·005 for PR4/PRB24; 69/103 [67%, 57–76], p<0·0001 for PRB48; and 77/103 [75%, 65–83], p<0·0001 for PR4/PRB44;
vs 39/104 [38%, 28–48] for PR48 control). Low-dose ribavirin was associated with a high rate of viral breakthrough (16/59 [27%]), and a rate of relapse (six of 27 [22%]) similar to control (12/51 [24%]). Boceprevir-based groups had higher rates of anaemia (227/416 [55%]
vs 35/104 [34%]) and dysgeusia (111/416 [27%]
vs nine of 104 [9%]) than did the control group.
In patients with untreated genotype 1 chronic hepatitis C infection, the addition of the direct-acting antiviral agent boceprevir to standard treatment with peginterferon and ribavirin after a 4-week lead-in seems to have the potential to double the sustained response rate compared with that recorded with standard treatment alone.
Merck
Living on the edge: utilising lidar data to assess the importance of vegetation structure for avian diversity in fragmented woodlands and their edges
Context: In agricultural landscapes, small woodland patches can be important wildlife refuges. Their value in maintaining biodiversity may, however, be compromised by isolation, and so knowledge about the role of habitat structure is vital to understand the drivers of diversity. This study examined how avian diversity and abundance were related to habitat structure in four small woods in an agricultural landscape in eastern England. Objectives: The aims were to examine the edge effect on bird diversity and abundance, and the contributory role of vegetation structure. Specifically: what is the role of vegetation structure on edge effects, and which edge structures support the greatest bird diversity? Methods: Annual breeding bird census data for 28 species were combined with airborne lidar data in linear mixed models fitted separately at (i) the whole wood level, and (ii) for the woodland edges only. Results: Despite relatively small woodland areas (4.9–9.4 ha), bird diversity increased significantly towards the edges, being driven in part by vegetation structure. At the whole woods level, diversity was positively associated with increased vegetation above 0.5 m and especially with increasing vegetation density in the understorey layer, which was more abundant at the woodland edges. Diversity along the edges was largely driven by the density of vegetation below 4 m. Conclusions: The results demonstrate that bird diversity was maximised by a diverse vegetation structure across the wood and especially a dense understorey along the edge. These findings can assist bird conservation by guiding habitat management of remaining woodland patches
ELEVATED PHENYLACETIC ACID LEVELS DO NOT CORRELATE WITH ADVERSE EVENTS IN PATIENTS WITH UREA CYCLE DISORDERS OR HEPATIC ENCEPHALOPATHY AND CAN BE PREDICTED BASED ON THE PLASMA PAA TO PAGN RATIO
Background Phenylacetic acid (PAA) is the active moiety in sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB, HPN-100), both are approved for treatment of urea cycle disorders (UCDs) - rare genetic disorders characterized by hyperammonemia. PAA is conjugated with glutamine in the liver to form phenylacetyleglutamine (PAGN), which is excreted in urine. PAA plasma levels ≥500 μg/dL have been reported to be associated with reversible neurological adverse events (AEs) in cancer patients receiving PAA intravenously. Therefore, we have investigated the relationship between PAA levels and neurological AEs in patients treated with these PAA pro-drugs as well as approaches to identifying patients most likely to experience high PAA levels. Methods The relationship between nervous system AEs, PAA levels and the ratio of plasma PAA to PAGN were examined in 4683 blood samples taken serially from: [1] healthy adults [2], UCD patients ≥2 months of age, and [3] patients with cirrhosis and hepatic encephalopathy (HE). The plasma ratio of PAA to PAGN was analyzed with respect to its utility in identifying patients at risk of high PAA values. Results Only 0.2% (11) of 4683 samples exceeded 500 ug/ml. There was no relationship between neurological AEs and PAA levels in UCD or HE patients, but transient AEs including headache and nausea that correlated with PAA levels were observed in healthy adults. Irrespective of population, a curvilinear relationship was observed between PAA levels and the plasma PAA:PAGN ratio, and a ratio > 2.5 (both in μg/mL) in a random blood draw identified patients at risk for PAA levels > 500 μg/ml. Conclusions The presence of a relationship between PAA levels and reversible AEs in healthy adults but not in UCD or HE patients may reflect intrinsic differences among the populations and/or metabolic adaptation with continued dosing. The plasma PAA:PAGN ratio is a functional measure of the rate of PAA metabolism and represents a useful dosing biomarker
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