2,417 research outputs found
Predicting Secondary Structures, Contact Numbers, and Residue-wise Contact Orders of Native Protein Structure from Amino Acid Sequence by Critical Random Networks
Prediction of one-dimensional protein structures such as secondary structures
and contact numbers is useful for the three-dimensional structure prediction
and important for the understanding of sequence-structure relationship. Here we
present a new machine-learning method, critical random networks (CRNs), for
predicting one-dimensional structures, and apply it, with position-specific
scoring matrices, to the prediction of secondary structures (SS), contact
numbers (CN), and residue-wise contact orders (RWCO). The present method
achieves, on average, accuracy of 77.8% for SS, correlation coefficients
of 0.726 and 0.601 for CN and RWCO, respectively. The accuracy of the SS
prediction is comparable to other state-of-the-art methods, and that of the CN
prediction is a significant improvement over previous methods. We give a
detailed formulation of critical random networks-based prediction scheme, and
examine the context-dependence of prediction accuracies. In order to study the
nonlinear and multi-body effects, we compare the CRNs-based method with a
purely linear method based on position-specific scoring matrices. Although not
superior to the CRNs-based method, the surprisingly good accuracy achieved by
the linear method highlights the difficulty in extracting structural features
of higher order from amino acid sequence beyond that provided by the
position-specific scoring matrices.Comment: 20 pages, 1 figure, 5 tables; minor revision; accepted for
publication in BIOPHYSIC
A new variant in signal peptide of the human luteinizing hormone receptor (LHCGR) affects receptor biogenesis causing leydig cell hypoplasia
The human luteinizing hormone/chorionic gonadotropin receptor (LHCGR) plays a fundamental role in male and female reproduction. In males, loss-of-function mutations in LHCGR have been associated with distinct degrees of impairment in pre- and postnatal testosterone secretion resulting in a variable phenotypic spectrum, classified as Leydig cell hypoplasia (LCH) type 1 (complete LH resistance and disorder of sex differentiation) and type 2 (partial LH resistance with impaired masculinization and fertility).Here, we report the case of an adolescent who came to the pediatric endocrinologist at the age of 12 years old for micropenis and cryptorchidism. Testis biopsy showed profound Leydig cell hypoplasia and absent germinal line elements (Sertoli-only syndrome). The sequence analysis of the LHCGR gene showed the presence of a compound heterozygosity, being one variation, c.1847C>A p.S616Y, already described in association to Hypergonadotropic Hypogonadism (HH), and the other, c.29 C>T p.L10P, a new identified variant in the putative signal peptide of LHCGR. Functional and structural studies provide first evidence that LHCGR have a functional and cleavable signal peptide required for receptor biogenesis. Moreover, we demonstrate the pathogenic role of the novel p.L10P allelic variant, which has to be considered a loss-of-function mutation significantly contributing, in compound heterozygosity with p.S616Y, to the Leydig cell hypoplasia type 2 observed in our patient
Correlation functions of scattering matrix elements in microwave cavities with strong absorption
The scattering matrix was measured for microwave cavities with two antennas.
It was analyzed in the regime of overlapping resonances. The theoretical
description in terms of a statistical scattering matrix and the rescaled
Breit-Wigner approximation has been applied to this regime. The experimental
results for the auto-correlation function show that the absorption in the
cavity walls yields an exponential decay. This behavior can only be modeled
using a large number of weakly coupled channels. In comparison to the
auto-correlation functions, the cross-correlation functions of the diagonal
S-matrix elements display a more pronounced difference between regular and
chaotic systems
Evolutionary Multi-Objective Design of SARS-CoV-2 Protease Inhibitor Candidates
Computational drug design based on artificial intelligence is an emerging
research area. At the time of writing this paper, the world suffers from an
outbreak of the coronavirus SARS-CoV-2. A promising way to stop the virus
replication is via protease inhibition. We propose an evolutionary
multi-objective algorithm (EMOA) to design potential protease inhibitors for
SARS-CoV-2's main protease. Based on the SELFIES representation the EMOA
maximizes the binding of candidate ligands to the protein using the docking
tool QuickVina 2, while at the same time taking into account further objectives
like drug-likeliness or the fulfillment of filter constraints. The experimental
part analyzes the evolutionary process and discusses the inhibitor candidates.Comment: 15 pages, 7 figures, submitted to PPSN 202
Flux Modulations seen by the Muon Veto of the GERDA Experiment
The GERDA experiment at LNGS of INFN is equipped with an active muon veto.
The main part of the system is a water Cherenkov veto with 66~PMTs in the water
tank surrounding the GERDA cryostat. The muon flux recorded by this veto shows
a seasonal modulation. Two effects have been identified which are caused by
secondary muons from the CNGS neutrino beam (2.2 %) and a temperature
modulation of the atmosphere (1.4 %). A mean cosmic muon rate of /(sm) was found in good agreement with other experiments at
LNGS at a depth of 3500~meter water equivalent.Comment: 7 pages, 6 figure
Limit on the Radiative Neutrinoless Double Electron Capture of Ar from GERDA Phase I
Neutrinoless double electron capture is a process that, if detected, would
give evidence of lepton number violation and the Majorana nature of neutrinos.
A search for neutrinoless double electron capture of Ar has been
performed with germanium detectors installed in liquid argon using data from
Phase I of the GERmanium Detector Array (GERDA) experiment at the Gran Sasso
Laboratory of INFN, Italy. No signal was observed and an experimental lower
limit on the half-life of the radiative neutrinoless double electron capture of
Ar was established: 3.6 10 yr at 90 % C.I.Comment: 7 pages, 3 figure
No Evolutionary Shift in the Mating System of North American Ambrosia artemisiifolia (Asteraceae) Following Its Introduction to China
The mating system plays a key role during the process of plant invasion. Contemporary evolution of uniparental reproduction (selfing or asexuality) can relieve the challenges of mate limitation in colonizing populations by providing reproductive assurance. Here we examined aspects of the genetics of colonization in Ambrosia artemisiifolia, a North American native that is invasive in China. This species has been found to possess a strong self-incompatibility system and have high outcrossing rates in North America and we examined whether there has been an evolutionary shift towards the dependence on selfing in the introduced range. Specifically, we estimated outcrossing rates in one native and five invasive populations and compared levels of genetic diversity between North America and China. Based on six microsatellite loci we found that, like the native North American population, all five Chinese populations possessed a completely outcrossing mating system. The estimates of paternity correlations were low, ranging from 0.028â0.122, which suggests that populations possessed âŒ8â36 pollen donor parents contributing to each maternal plant in the invasive populations. High levels of genetic diversity for both native and invasive populations were found with the unbiased estimate of gene diversity ranging from 0.262â0.289 for both geographic ranges based on AFLP markers. Our results demonstrate that there has been no evolutionary shift from outcrossing to selfing during A. artemisiifolia's invasion of China. Furthermore, high levels of genetic variation in North America and China indicate that there has been no erosion of genetic variance due to a bottleneck during the introduction process. We suggest that the successful invasion of A. artemisiifolia into Asia was facilitated by repeated introductions from multiple source populations in the native range creating a diverse gene pool within Chinese populations
Stress related epigenetic changes may explain opportunistic success in biological invasions in Antipode mussels
Different environmental factors could induce epigenetic changes, which are likely involved in the biological invasion process. Some of these factors are driven by humans as, for example, the pollution and deliberate or accidental introductions and others are due to natural conditions such as salinity. In this study, we have analysed the relationship between different stress factors: time in the new location, pollution and salinity with the methylation changes that could be involved in the invasive species tolerance to new environments. For this purpose, we have analysed two different musselsâ species, reciprocally introduced in antipode areas: the Mediterranean blue mussel Mytilus galloprovincialis and the New Zealand pygmy mussel Xenostrobus securis, widely recognized invaders outside their native distribution ranges. The demetylathion was higher in more stressed population, supporting the idea of epigenetic is involved in plasticity process. These results can open a new management protocols, using the epigenetic signals as potential pollution monitoring tool. We could use these epigenetic marks to recognise the invasive status in a population and determine potential biopollutants
Innovation Contests with Entry Auction
We consider procurement of an innovation from heterogeneous sellers. Innovations are random but depend on unobservable effort and private information. We compare two procurement mechanisms where potential sellers first bid in an auction for admission to an innovation contest. After the contest, an innovation is procured employing either a fixed prize or a first-price auction. We characterize Bayesian Nash equilibria such that both mechanisms are payoff-equivalent and induce the same efforts and innovations. In these equilibria, signaling in the entry auction does not occur since contestants play a simple strategy that does not depend on rivals' private information
- âŠ