2,513 research outputs found
V1R promoters are well conserved and exhibit common putative regulatory motifs
<p>Abstract</p> <p>Background</p> <p>The mouse vomeronasal organ (VNO) processes chemosensory information, including pheromone signals that influence reproductive behaviors. The sensory neurons of the VNO express two types of chemosensory receptors, V1R and V2R. There are ~165 V1R genes in the mouse genome that have been classified into ~12 divergent subfamilies. Each sensory neuron of the apical compartment of the VNO transcribes only one of the repertoire of V1R genes. A model for mutually exclusive V1R transcription in these cells has been proposed in which each V1R gene might compete stochastically for a single transcriptional complex. This model predicts that the large repertoire of divergent V1R genes in the mouse genome contains common regulatory elements. In this study, we have characterized V1R promoter regions by comparative genomics and by mapping transcription start sites.</p> <p>Results</p> <p>We find that transcription is initiated from ~1 kb promoter regions that are well conserved within V1R subfamilies. While cross-subfamily homology is not evident by traditional methods, we developed a heuristic motif-searching tool, <it>LogoAlign</it>, and applied this tool to identify motifs shared within the promoters of all V1R genes. Our motif-searching tool exhibits rapid convergence to a relatively small number of non-redundant solutions (97% convergence). We also find that the best motifs contain significantly more information than those identified in controls, and that these motifs are more likely to be found in the immediate vicinity of transcription start sites than elsewhere in gene blocks. The best motifs occur near transcription start sites of ~90% of all V1R genes and across all of the divergent subfamilies. Therefore, these motifs are candidate binding sites for transcription factors involved in V1R co-regulation.</p> <p>Conclusion</p> <p>Our analyses show that V1R subfamilies have broad and well conserved promoter regions from which transcription is initiated. Results from a new motif-finding algorithm, <it>LogoAlign</it>, designed for this context and more generally for searching large, hierarchical datasets, suggest the existence of common information-rich regulatory motifs that are shared across otherwise divergent V1R subfamilies.</p
Bimodules in bordered Heegaard Floer homology
Bordered Heegaard Floer homology is a three-manifold invariant which
associates to a surface F an algebra A(F) and to a three-manifold Y with
boundary identified with F a module over A(F). In this paper, we establish
naturality properties of this invariant. Changing the diffeomorphism between F
and the boundary of Y tensors the bordered invariant with a suitable bimodule
over A(F). These bimodules give an action of a suitably based mapping class
group on the category of modules over A(F). The Hochschild homology of such a
bimodule is identified with the knot Floer homology of the associated open book
decomposition. In the course of establishing these results, we also calculate
the homology of A(F). We also prove a duality theorem relating the two versions
of the 3-manifold invariant. Finally, in the case of a genus one surface, we
calculate the mapping class group action explicitly. This completes the
description of bordered Heegaard Floer homology for knot complements in terms
of the knot Floer homology.Comment: 153 pages, 29 figures; v4: Address referee comment
Dynamic evolution of V1R putative pheromone receptors between Mus musculus and Mus spretus
<p>Abstract</p> <p>Background</p> <p>The mammalian vomeronasal organ (VNO) expresses two G-protein coupled receptor gene families that mediate pheromone responses, the V1R and V2R receptor genes. In rodents, there are ~150 V1R genes comprising 12 subfamilies organized in gene clusters at multiple chromosomal locations. Previously, we showed that several of these subfamilies had been extensively modulated by gene duplications, deletions, and gene conversions around the time of the evolutionary split of the mouse and rat lineages, consistent with the hypothesis that V1R repertoires might be involved in reinforcing speciation events. Here, we generated genome sequence for one large cluster containing two V1R subfamilies in Mus spretus, a closely related and sympatric species to Mus musculus, and investigated evolutionary change in these repertoires along the two mouse lineages.</p> <p>Results</p> <p>We describe a comparison of spretus and musculus with respect to genome organization and synteny, as well as V1R gene content and phylogeny, with reference to previous observations made between mouse and rat. Unlike the mouse-rat comparisons, synteny seems to be largely conserved between the two mouse species. Disruption of local synteny is generally associated with differences in repeat content, although these differences appear to arise more from deletion than new integrations. Even though unambiguous V1R orthology is evident, we observe dynamic modulation of the functional repertoires, with two of seven <it>V1Rb </it>and one of eleven <it>V1Ra </it>genes lost in spretus, two <it>V1Ra </it>genes becoming pseudogenes in musculus, two additional orthologous pairs apparently subject to strong adaptive selection, and another divergent orthologous pair that apparently was subjected to gene conversion.</p> <p>Conclusion</p> <p>Therefore, eight of the 18 (~44%) presumptive <it>V1Ra/V1Rb </it>genes in the musculus-spretus ancestor appear to have undergone functional modulation since these two species diverged. As compared to the rat-mouse split, where modulation is evident by independent expansions of these two V1R subfamilies, divergence between musculus and spretus has arisen more by mutations within coding sequences. These results support the hypothesis that adaptive changes in functional V1R repertoires contribute to the delineation of very closely related species.</p
Comparing first-principles density functionals plus corrections for the lattice dynamics of YBaCuO
The enigmatic mechanism underlying unconventional high-temperature
superconductivity, especially the role of lattice dynamics, has remained a
subject of debate. Theoretical insights have long been hindered due to the lack
of an accurate first-principles description of the lattice dynamics of
cuprates. Recently, using the r2SCAN meta-GGA functional, we were able to
achieve accurate phonon spectra of an insulating cuprate YBaCuO,
and discover significant magnetoelastic coupling in experimentally interesting
Cu-O bond stretching optical modes [Phys. Rev. B 107, 045126 (2023)]. We extend
this work by comparing PBE and r2SCAN performances with corrections from the
on-site Hubbard U and the D4 van der Waals (vdW) methods, aiming at further
understanding on both the materials science side and the density functional
side. We demonstrate the importance of vdW and self-interaction corrections for
accurate first-principles YBa2 Cu3 O6 lattice dynamics. Since r2SCAN by itself
partially accounts for these effects, the good performance of r2SCAN is now
more fully explained. In addition, the performances of the Tao-Mo series of
meta-GGAs, which are constructed in a different way from SCAN/r2SCAN, are also
compared and discussed.Comment: arXiv admin note: text overlap with arXiv:2210.0656
Clinical relevance of findings in trials of CBT for depression
Cognitive behavioural therapy (CBT) is beneficial in depression. Symptom scores can be translated into Clinical Global Impression (CGI) scale scores to indicate clinical relevance. We aimed to assess the clinical relevance of findings of randomised controlled trials (RCTs) of CBT in depression. We identified RCTs of CBT that used the Hamilton Rating Scale for Depression (HAMD). HAMD scores were translated into Clinical Global Impression – Change scale (CGI-I) scores to measure clinical relevance. One hundred and seventy datasets from 82 studies were included. The mean percentage HAMD change for treatment arms was 53.66%, and 29.81% for control arms, a statistically significant difference. Combined active therapies showed the biggest improvement on CGI-I score, followed by CBT alone. All active treatments had better than expected HAMD percentage reduction and CGI-I scores. CBT has a clinically relevant effect in depression, with a notional CGI-I score of 2.2, indicating a significant clinical response. The non-specific or placebo effect of being in a psychotherapy trial was a 29% reduction of HAMD
Efficacy and safety of a novel oral isoxazoline, sarolaner (Simparica™), for the treatment of sarcoptic mange in dogs
AbstractThe efficacy of the novel isoxazoline, sarolaner (Simparica™) was investigated in dogs with clinical signs consistent with sarcoptic mange and harbouring natural infestations of Sarcoptes scabiei. One placebo-controlled laboratory study and one multi-centred field study with a commercial comparator containing imidacloprid/moxidectin (Advocate® spot-on) were conducted. Oral or topical treatments were administered on Days 0 and 30. Up to 10 skin scrapings were taken for the assessment of S. scabiei infestations from each dog before treatment and on Days 14, 30, 44 and 60 in the laboratory study, and on Days 30 and 60 in the field study. In the laboratory study, efficacy was calculated based on the percent reduction of mean live mite counts compared to the placebo group. In the field study parasitological cure rate (% dogs free of mites) was determined and non-inferiority of sarolaner to the control product was assessed.In the laboratory study 44 mixed breed dogs were enrolled in four batches. Due to decreasing mite counts in the placebo treated dogs, immunosuppression with dexamethasone (0.4mg/kg three times per week for two weeks) was initiated in all dogs on study at that time (n=6) and those subsequently enrolled (n=14). In the field study, dogs were enrolled in a 2:1 ratio (sarolaner:comparator); 79 dogs were assessed for efficacy and safety, and an additional 45 dogs were assessed for safety only. There were no treatment related adverse events in either study.In the laboratory study, no mites were found on any sarolaner-treated dogs 14 days after the first treatment except for one dog that had a single mite on Day 44. In the field study, the parasitological cure rate was 88.7% and 100% in the sarolaner group and 84.6% and 96.0% in the imidacloprid/moxidectin group, on Days 30 and 60, respectively. Statistical analysis showed that sarolaner was non-inferior to imidacloprid/moxidectin at both time points. The clinical signs of sarcoptic mange, including hair loss, papules, pruritus, erythema, and scaling/crusting improved throughout the study.Sarolaner was safe, achieved 100% reduction in the numbers of S. scabiei detected and resulted in marked improvement of the clinical signs of sarcoptic mange in dogs following two monthly oral administrations
The Antarctic Submillimeter Telescope and Remote Observatory (AST/RO)
AST/RO, a 1.7 m diameter telescope for astronomy and aeronomy studies at
wavelengths between 200 and 2000 microns, was installed at the South Pole
during the 1994-1995 Austral summer. The telescope operates continuously
through the Austral winter, and is being used primarily for spectroscopic
studies of neutral atomic carbon and carbon monoxide in the interstellar medium
of the Milky Way and the Magellanic Clouds. The South Pole environment is
unique among observatory sites for unusually low wind speeds, low absolute
humidity, and the consistent clarity of the submillimeter sky. Four heterodyne
receivers, an array receiver, three acousto-optical spectrometers, and an array
spectrometer are installed. A Fabry-Perot spectrometer using a bolometric array
and a Terahertz receiver are in development. Telescope pointing, focus, and
calibration methods as well as the unique working environment and logistical
requirements of the South Pole are described.Comment: 57 pages, 15 figures. Submitted to PAS
Precision atomic gravimeter based on Bragg diffraction
We present a precision gravimeter based on coherent Bragg diffraction of
freely falling cold atoms. Traditionally, atomic gravimeters have used
stimulated Raman transitions to separate clouds in momentum space by driving
transitions between two internal atomic states. Bragg interferometers utilize
only a single internal state, and can therefore be less susceptible to
environmental perturbations. Here we show that atoms extracted from a
magneto-optical trap using an accelerating optical lattice are a suitable
source for a Bragg atom interferometer, allowing efficient beamsplitting and
subsequent separation of momentum states for detection. Despite the inherently
multi-state nature of atom diffraction, we are able to build a Mach-Zehnder
interferometer using Bragg scattering which achieves a sensitivity to the
gravitational acceleration of with an
integration time of 1000s. The device can also be converted to a gravity
gradiometer by a simple modification of the light pulse sequence.Comment: 13 pages, 11 figure
Privacy in Multimodal Federated Human Activity Recognition
Human Activity Recognition (HAR) training data is often privacy-sensitive or
held by non-cooperative entities. Federated Learning (FL) addresses such
concerns by training ML models on edge clients. This work studies the impact of
privacy in federated HAR at a user, environment, and sensor level. We show that
the performance of FL for HAR depends on the assumed privacy level of the FL
system and primarily upon the colocation of data from different sensors. By
avoiding data sharing and assuming privacy at the human or environment level,
as prior works have done, the accuracy decreases by 5-7%. However, extending
this to the modality level and strictly separating sensor data between multiple
clients may decrease the accuracy by 19-42%. As this form of privacy is
necessary for the ethical utilisation of passive sensing methods in HAR, we
implement a system where clients mutually train both a general FL model and a
group-level one per modality. Our evaluation shows that this method leads to
only a 7-13% decrease in accuracy, making it possible to build HAR systems with
diverse hardware.Comment: In 3rd On-Device Intelligence Workshop at MLSys 2023, 8 page
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