206 research outputs found
Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.
Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy. Incoming peptides are recognized according to the global stability of the final pMHC-I product and anneal in a native-like conformation to be edited by TAPBPR. Our results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. These results suggest a similar mechanism for the function of tapasin in the peptide-loading complex
Traces of past activity in the Galactic Centre
The Milky Way centre hosts a supermassive Black Hole (BH) with a mass of
~4*10^6 M_Sun. Sgr A*, its electromagnetic counterpart, currently appears as an
extremely weak source with a luminosity L~10^-9 L_Edd. The lowest known
Eddington ratio BH. However, it was not always so; traces of "glorious" active
periods can be found in the surrounding medium. We review here our current view
of the X-ray emission from the Galactic Center (GC) and its environment, and
the expected signatures (e.g. X-ray reflection) of a past flare. We discuss the
history of Sgr A*'s past activity and its impact on the surrounding medium. The
structure of the Central Molecular Zone (CMZ) has not changed significantly
since the last active phase of Sgr A*. This relic torus provides us with the
opportunity to image the structure of an AGN torus in exquisite detail.Comment: Invited refereed review. Chapter of the book: "Cosmic ray induced
phenomenology in star forming environments" (eds. Olaf Reimer and Diego F.
Torres
The next-generation ARC middleware
The Advanced Resource Connector (ARC) is a light-weight, non-intrusive, simple yet powerful Grid middleware capable of connecting highly heterogeneous computing and storage resources. ARC aims at providing general purpose, flexible, collaborative computing environments suitable for a range of uses, both in science and business. The server side offers the fundamental job execution management, information and data capabilities required for a Grid. Users are provided with an easy to install and use client which provides a basic toolbox for job- and data management. The KnowARC project developed the next-generation ARC middleware, implemented as Web Services with the aim of standard-compliant interoperability
Magnetic fields in supernova remnants and pulsar-wind nebulae
We review the observations of supernova remnants (SNRs) and pulsar-wind
nebulae (PWNe) that give information on the strength and orientation of
magnetic fields. Radio polarimetry gives the degree of order of magnetic
fields, and the orientation of the ordered component. Many young shell
supernova remnants show evidence for synchrotron X-ray emission. The spatial
analysis of this emission suggests that magnetic fields are amplified by one to
two orders of magnitude in strong shocks. Detection of several remnants in TeV
gamma rays implies a lower limit on the magnetic-field strength (or a
measurement, if the emission process is inverse-Compton upscattering of cosmic
microwave background photons). Upper limits to GeV emission similarly provide
lower limits on magnetic-field strengths. In the historical shell remnants,
lower limits on B range from 25 to 1000 microGauss. Two remnants show
variability of synchrotron X-ray emission with a timescale of years. If this
timescale is the electron-acceleration or radiative loss timescale, magnetic
fields of order 1 mG are also implied. In pulsar-wind nebulae, equipartition
arguments and dynamical modeling can be used to infer magnetic-field strengths
anywhere from about 5 microGauss to 1 mG. Polarized fractions are considerably
higher than in SNRs, ranging to 50 or 60% in some cases; magnetic-field
geometries often suggest a toroidal structure around the pulsar, but this is
not universal. Viewing-angle effects undoubtedly play a role. MHD models of
radio emission in shell SNRs show that different orientations of upstream
magnetic field, and different assumptions about electron acceleration, predict
different radio morphology. In the remnant of SN 1006, such comparisons imply a
magnetic-field orientation connecting the bright limbs, with a non-negligible
gradient of its strength across the remnant.Comment: 20 pages, 24 figures; to be published in SpSciRev. Minor wording
change in Abstrac
Characterizing early drug resistance-related events using geometric ensembles from HIV protease dynamics:
The use of antiretrovirals (ARVs) has drastically improved the life quality and expectancy of HIV patients since their introduction in health care. Several millions are still afflicted worldwide by HIV and ARV resistance is a constant concern for both healthcare practitioners and patients, as while treatment options are finite, the virus constantly adapts via complex mutation patterns to select for resistant strains under the pressure of drug treatment. The HIV protease is a crucial enzyme for viral maturation and has been a game changing drug target since the first application. Due to similarities in protease inhibitor designs, drug cross-resistance is not uncommon across ARVs of the same class
Status report on emerging photovoltaics
\ua9 2023 Society of Photo-Optical Instrumentation Engineers (SPIE).This report provides a snapshot of emerging photovoltaic (PV) technologies. It consists of concise contributions from experts in a wide range of fields including silicon, thin film, III-V, perovskite, organic, and dye-sensitized PVs. Strategies for exceeding the detailed balance limit and for light managing are presented, followed by a section detailing key applications and commercialization pathways. A section on sustainability then discusses the need for minimization of the environmental footprint in PV manufacturing and recycling. The report concludes with a perspective based on broad survey questions presented to the contributing authors regarding the needs and future evolution of PV
Higher ethical objective (Maqasid al-Shari'ah) augmented framework for Islamic banks : assessing the ethical performance and exploring its determinants.
This study utilises higher objectives postulated in Islamic moral economy or the maqasid al-Shari’ah theoretical framework’s novel approach in evaluating the ethical, social, environmental and financial performance of Islamic banks. Maqasid al-Shari’ah is interpreted as achieving social good as a consequence in addition to well-being and, hence, it goes beyond traditional (voluntary) social responsibility. This study also explores the major determinants that affect maqasid performance as expressed through disclosure analysis. By expanding the traditional maqasid al-Shari’ah,, we develop a comprehensive evaluation framework in the form of a maqasid index, which is subjected to a rigorous disclosure analysis. Furthermore, in identifying the main determinants of the maqasid disclosure performance, panel data analysis is used by including several key variables alongside political and socio-economic environment, ownership structures, and corporate and Shari’ah governance-related factors. The sample includes 33 full-fledged Islamic banks from 12 countries for the period of 2008–2016. The findings show that although during the nine-year period the disclosure of maqasid performance of the sampled Islamic banks has improved, this is still short of ‘best practices’. Through panel data analysis, this study finds that the Muslim population indicator, CEO duality, Shari’ah governance, and leverage variables positively impact the disclosure of maqasid performance. However, the effect of GDP, financial development and human development index of the country, its political and civil rights, institutional ownership, and a higher share of independent directors have an overall negative impact on the maqasid performance. The findings reported in this study identify complex and multi-faceted relations between external market realities, corporate and Shari’ah governance mechanisms, and maqasid performance
Mitochondrial-Nuclear DNA Interactions Contribute to the Regulation of Nuclear Transcript Levels as Part of the Inter-Organelle Communication System
Nuclear and mitochondrial organelles must maintain a communication system. Loci on the mitochondrial genome were recently reported to interact with nuclear loci. To determine whether this is part of a DNA based communication system we used genome conformation capture to map the global network of DNA-DNA interactions between the mitochondrial and nuclear genomes (Mito-nDNA) in Saccharomyces cerevisiae cells grown under three different metabolic conditions. The interactions that form between mitochondrial and nuclear loci are dependent on the metabolic state of the yeast. Moreover, the frequency of specific mitochondrial - nuclear interactions (i.e. COX1-MSY1 and Q0182-RSM7) showed significant reductions in the absence of mitochondrial encoded reverse transcriptase machinery. Furthermore, these reductions correlated with increases in the transcript levels of the nuclear loci (MSY1 and RSM7). We propose that these interactions represent an inter-organelle DNA mediated communication system and that reverse transcription of mitochondrial RNA plays a role in this process
Towards a Processual Microbial Ontology
types: ArticleStandard microbial evolutionary ontology is organized according to a
nested hierarchy of entities at various levels of biological organization. It typically
detects and defines these entities in relation to the most stable aspects of evolutionary
processes, by identifying lineages evolving by a process of vertical inheritance
from an ancestral entity. However, recent advances in microbiology indicate
that such an ontology has important limitations. The various dynamics detected
within microbiological systems reveal that a focus on the most stable entities (or
features of entities) over time inevitably underestimates the extent and nature of
microbial diversity. These dynamics are not the outcome of the process of vertical
descent alone. Other processes, often involving causal interactions between entities
from distinct levels of biological organisation, or operating at different time scales,
are responsible not only for the destabilisation of pre-existing entities, but also for
the emergence and stabilisation of novel entities in the microbial world. In this
article we consider microbial entities as more or less stabilised functional wholes,
and sketch a network-based ontology that can represent a diverse set of processes
including, for example, as well as phylogenetic relations, interactions that stabilise
or destabilise the interacting entities, spatial relations, ecological connections, and
genetic exchanges. We use this pluralistic framework for evaluating (i) the existing
ontological assumptions in evolution (e.g. whether currently recognized entities are
adequate for understanding the causes of change and stabilisation in the microbial
world), and (ii) for identifying hidden ontological kinds, essentially invisible from
within a more limited perspective. We propose to recognize additional classes of
entities that provide new insights into the structure of the microbial world, namely ‘‘processually equivalent’’ entities, ‘‘processually versatile’’ entities, and ‘‘stabilized’’
entities.Economic and Social Research Council, U
Testing the inverse-Compton catastrophe scenario in the intra-day variable blazar S5 0716+71. I. Simultaneous broadband observations during November 2003
Some intra-day variable, compact extra-galactic radio sources show brightness
temperatures severely exceeding 10^{12} K, the limit set by catastrophic
inverse-Compton (IC) cooling in sources of incoherent synchrotron radiation.
The violation of the IC limit, possible under non-stationary conditions, would
lead to IC avalanches in the soft-gamma-ray energy band during transient
periods. For the first time, broadband signatures of possible IC catastrophes
were searched for in S5 0716+71. A multifrequency observing campaign targetting
S5 0716+71 was carried out in November 2003 under the framework of the European
Network for the Investigation of Galactic nuclei through Multifrequency
Analysis (ENIGMA) together with a campaign by the Whole Earth Blazar Telescope
(WEBT), involving a pointing by the soft-gamma-ray satellite INTEGRAL, optical,
near-infrared, sub-millimeter, millimeter, radio, and Very Long Baseline Array
(VLBA) monitoring. S5 0716+71 was very bright at radio frequencies and in a
rather faint optical state during the INTEGRAL pointing; significant inter-day
and low intra-day variability was recorded in the radio regime, while typical
fast variability features were observed in the optical band. No correlation was
found between the radio and optical emission. The source was not detected by
INTEGRAL, neither by the X-ray monitor JEM-X nor by the gamma-ray imager ISGRI,
but upper limits to the source emission in the 3-200 keV energy band were
estimated. A brightness temperature Tb>2.1x10^{14} K was inferred from the
radio variability, but no corresponding signatures of IC avalanches were
recorded at higher energies. The absence of IC-catastrophe signatures provides
either a lower limit delta>8 to the Doppler factor affecting the radio emission
or strong constraints for modelling of the Compton catastrophes in S5 0716+71.Comment: 15 pages, 3 EPS figures, 3 tables, to appear in A&
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