Miracle-dz/UniFAR-FTUs huggingface dataset:
Signaling Specificity and Kinetics of the Human Metabotropic Glutamate Receptors

Metabotropic glutamate receptors (mGluRs) are obligate dimer G protein coupled receptors that can all function as homodimers. Here, each mGluR homodimer was examined for its G protein coupling profile using a bioluminescence resonance energy transfer-based assay that detects the interaction between a split YFP-tagged Gβ1γ2 and a Nanoluciferase tagged free Gβγ sensor, MAS-GRK3-ct- nanoluciferase with 14 specific Gα proteins heterologously expressed, representing each family. Canonically, the group II and III mGluRs (2 and 3 and 4, 6, 7, and 8, respectively) are thought to couple to Gi/o exclusively. In addition, the group I mGluRs (1 and 5) are known to couple to the Gq/11 family and generally thought to also couple to the pertussis toxin-sensitive Gi/o family some reports have suggested Gs coupling is possible as cAMP elevations have been noted. In this study, coupling was observed with all eight mGluRs through the Gi/o proteins and only mGluR1 and mGluR5 through Gq/11, and, perhaps surprisingly, not G14. None activated any Gs protein. Interestingly, coupling was seen with the group I and II but not the group III mGluRs to G16. Slow but significant coupling to Gz was also seen with the group II receptors. SIGNIFICANCE STATEMENT Metabotropic glutamate receptor (mGluR)-G protein coupling has not been thoroughly examined, and some controversy remains about whether some mGluRs can activate Gαs family members. Here we examine the ability of each mGluR to activate representative members of every Gα protein family. While all mGluRs can activate Gαi/o proteins, only the group I mGluRs couple to Gαq/11, and no members of the family can activate Gαs family members, including the group I receptors alone or with positive allosteric modulators.
Evolution of the enhancer-rich regulatory region of the POU1F1 gene

Precise spatio-temporal expression of genes in organogenesis is regulated by the coordinated interplay of DNA elements such as promoter and enhancers present in the regulatory region of a given locus. POU1F1 transcription factor plays a crucial role in the development of somatotrophs, lactotrophs and thyrotrophs in the anterior pituitary gland, and in maintaining high expression of growth hormone, prolactin and TSH. In mouse, expression of POU1F1 is controlled by a region fenced by two CTCF sites, containing 5 upstream enhancer elements, designated E-A (5’ to 3’). We performed comparative sequence analysis of this regulatory region and discovered that three elements, B, C and E, are present in all vertebrate groups except Agnatha. One very long (>2kb) element (A) is unique to mammals suggesting a specific change in regulation of the gene in this group. Using DNA accessibility assay (ATAC-seq) we showed that conserved elements in anterior pituitary of four non-mammals are open, suggesting functionality as regulatory elements. We showed that, in many non-mammalian vertebrates, an additional upstream exon closely follows element E, leading to alternatively spliced transcripts. Here, element E functions as an alternative promoter, but in mammals this feature is lost, suggesting that conversion of alternative promoter to enhancer could be one evolutionary mechanism for enhancer birth. Our work shows that regulation of POU1F1 changed markedly during the course of vertebrate evolution, use of a small number of enhancer elements combined with alternative promoters in non-mammalian vertebrates being replaced by use of a unique combination of enhancers in mammals.
Macrophage inhibitor clodronate enhances liver transduction of lentiviral but not AAV vectors or mRNA lipid nanoparticles in vivo

Recently approved adeno-associated viral (AAV) vectors for liver monogenic diseases hemophilia A and B are exemplifying the success of liver-directed viral gene therapy. In parallel, additional strategies are rapidly emerging to overcome some inherent AAV limitations, such as non-persistence of episomal transgene in rapidly growing liver and immune response. Integrating lentiviral vectors and non-viral lipid nanoparticles encapsulating mRNA (LNP-mRNA) are rapidly being developed, currently at preclinical and clinical stages respectively. Macrophages are first effector cells of the innate immune response triggered by gene therapy vectors. Macrophage uptake and activation following administration of viral gene therapy and LNPs has been reported. In this study, we assessed the biodistribution of AAV, lentiviral and LNP-mRNA gene therapy following inhibition of tissue macrophages by clodronate liposomes in neonatal and juvenile mice. Juvenile clodronate-treated mice showed significant increase of lentiviral-transduced hepatocytes, and increasing trend of transduction was shown in neonatally-injected mice. In contrast, AAV- and LNP-mRNA-treated neonatal and juvenile animals did not show significant increase of liver biodistribution following clodronate administration. These findings will have translational application for liver-targeting gene therapy programmes.
ERBB signalling contributes to immune evasion in KRAS-driven lung adenocarcinoma

Immunotherapy is increasingly viewed as treatment of choice for lung cancer, however, clinical responses to immune checkpoint blockade remain highly unpredictable and are largely transient. A deeper mechanistic understanding of the dynamics of tumour:immune interactions is needed to drive rational development of improved treatment strategies. Progress is hampered by a paucity of autochthonous model systems in which to interrogate the 2-way interactions of immune responses to evolving tumours and vice-versa. Specifically, commonly used genetically engineered mouse models typically lack the genetic diversity needed to drive an adaptive immune response. APOBEC mutagenesis signatures are prominent in lung cancer and APOBEC activity is predicted to drive immune visibility through Cytidine deaminase activity, coupled with inaccurate DNA-repair responses. We therefore generated a CRE-inducible APOBEC3B allele, interbred with multiple oncogenic drivers of lung adenocarcinoma, and used the resulting mice to investigate the response to PD1 blockade at single cell resolution. SIGNIFICANCE Using our novel immune-visible model of KRas-driven autochthonous lung adenocarcinoma, we uncovered a surprising increase in tumour-cell expression of EGFR/ERBB ligands following treatment with α-PD1 and present evidence that transient ERBB blockade can restore immune surveillance in KRas mutant LuAd and combine effectively with immune checkpoint blockade.
Double-Blind, Multicenter Comparative Study of Sertraline and Amitriptyline in Hospitalized Patients with Major Depression

Sertraline is a selective serotonin reuptake inhibitor (SSRI) for which marketing approval has been obtained recently in Cermany. The results of several double-blind, placebo-controlled studies have demonstrated that sertraline has a clear antidepressive effect. However these studies have been conducted in outpatient populations. In the context of this rnulti-center study. a total of 160 inpatients were treated with sertra-line 50 - 150 mg or amitriptyline 75 - 225 mg over a period of 6 weeks in a double-blind fashion. Sixty-two patients in the ser-traline and 59 patients in the amitriptyline group were evaluated for efficacy in the according-to-protocol (ATP) population; 80 sertraline and 75 amitriptyline patients were evaluated for safety in the Intention-to-treat population (ITT). No statistically significant differences were detected between the two groups in the efficacy analysis performed on the basis of the Hamilton Depression Scale (HAM-D) total score and Clinical Global Irn-pression (CCI). Due to its sedating properties, amitriptyline was found to be significantly more effective with regard to the HAM-D factor "sleep disturbance". The safety analysis, which was based on the CGI, the global assessment at the end of study and a score for somatic adverse events (FSUCL) revealed statistically significant advantages of sertraline over arnitripty-line. Amitriptyline was associated with more autonomic and circulatory side effects. while epigastric complaints occurred more often with sertraline. The incidence of nausea - a typical SSRI side effect - was the same in both groups.
Thermographie multi-échelle par méthodes optiques sur gouttelettes et bulles micrométriques : applications aux nanoparticules irradiées par laser ultra-intense et aux édifices biomoléculaires en cours de déshydratation

Ce travail de these a eu pour but d'etudier la thermodynamique de petits objets (nanoparticules ou edifices biomoleculaires) dans des milieux fortement hors-equilibre. Deux milieux miroirs ont ete explores, a savoir des gouttelettes micrometriques chargees et des microbulles generees sous irradiation laser intense. Ces deux systemes sont par nature difficiles a sonder par des methodes traditionnelles, c'est pourquoi, une thermographie innovante multi-echelle par methodes optiques a ete developpee. Ainsi, une thermographie locale (au sein des nano-objets) et globale (dans le milieu environnant) a ete realisee. Cette thermographie utilise la fluorescence induite par laser - methode simple, non invasive et efficace pour fournir une mesure de temperature avec une bonne resolution spatiale, temporelle et thermique - grâce a des colorants thermochromiques directement en solution dans le milieu ou bien incorpores dans les nano-objets. Cette thermographie est egalement completee avec d'autres mesures physiques, notamment la taille des gouttelettes et des bulles micrometriques pour aller vers une etude thermodynamique exhaustive de ces systemes. Ces etudes thermodynamiques ont ete menees autour des deux thematiques : Edifices biomoleculaires dans des gouttelettes micrometriques chargees en cours de deshydratation. Les sources electrospray, devenues un outil incontournable en spectrometrie de masse, presentent une thermodynamique riche et encore mal comprise. Des mesures de taille et de temperature de gouttelettes micrometriques chargees en cours d'evaporation ont pu etre confrontees dans le but d'avoir une description thermodynamique complete d'une source electrospray. De plus, afin de pouvoir suivre la conformation des edifices biomoleculaires (proteines) en cours de deshydratation, le concept d'anisotropie de fluorescence comme sonde conformationnelle a ete valide en solution et pourra etre transpose pour une analyse in situ dans la plume de l'electrospray.Nanoparticules dans des microbulles generees sous irradiation laser intense. Il s'agit ici d'etudier l'influence de nanoparticules lors de la generation de microbulles par nano-cavitation induite par irradiation laser intense, thematique au coeur du projet « ERTIGO ». Le principal objectif scientifique de ce projet a ete d'obtenir une comprehension des mecanismes d'absorption d'une solution contenant des nanoparticules irradiees. A cet effet, une source lumineuse atypique (laser aleatoire) a ete employee
Rank Minimization-Based Fast Image Completion

We propose an image completion algorithm using a rank minimization framework. Based on the lowrank property of an image, we formulate image completion as a low-rank matrix completion problem. Then, we solve the optimization problem efficiently using the augmented Lagrange multiplier (ALM) method. Experiments show that the proposed algorithm provides comparable or even higher image qualities than state-of-the-art approaches, while demanding significantly lower computational resources.
Distributed space-time block coding for cooperative networks with multiple-antenna nodes

In this paper, we present an extension to our previous work on distributed space-time block coding where we considered cooperative networks with a large set of single-antenna decode-and-forward relays N. Here, we consider the general case where each relay node is equipped with N/sub T/ antennas and the destination node has N/sub R/ antennas. It is assumed that at any given time only a small, a priori unknown subset of nodes S C N is active. In the proposed scheme, the signal transmitted by an active node is the product of an information-carrying space-time block code (STBC) matrix, which is identical for all nodes, and a unique node signature matrix. It is shown that existing STBCs designed for N/sub c/ /spl ges/ 2 co-located antennas are a favorable choice for the code matrix guaranteeing a diversity order of d = min {N/sub c/N/sub R/, N/sub T/N/sub S/N/sub R/} if ns nodes are active. Simulation results show that a considerable gain can be achieved by using multiple-antenna nodes even if the antennas are highly correlated.
Forwards or backwards—regulatory focus orientation of offense and defense players in team sports

ABSTRACT Playing positions in team sports can be divided into two broad categories: offense players who typically prioritise scoring points over preventing the other team from scoring and defense players who typically prioritise preventing the opponents from scoring over scoring themselves. Thus, offense and defense players have very different approaches and goals within the game. It therefore seems likely that the players of these different positions also differ from each other in relevant motivational or self-regulatory characteristics such as their regulatory focus orientation. Because the definitions of regulatory promotion focus and regulatory prevention focus match very closely the definitions of offense and defense players, we hypothesised that offense players should have higher levels of promotion focus than defense players and that defense players should have higher levels of prevention focus than offense players. Using data from a preregistered large-scale online survey on playing positions and personality in team sports (N = 2,185 athletes from 18 different team sports), we found in linear regression analyses that offense players indeed had significantly higher levels of promotion focus, whereas defense players indeed had significantly higher levels of prevention focus. For prevention focus, these differences were also robust to both a different classification of offense and defense and to the inclusion of moderators. Overall, these findings suggest that regulatory focus may play an important role in team sports. Future research should therefore further examine these effects, their mechanisms, and their consequences in terms of sport satisfaction, performance, and regulatory fit.
Homotopy equivalence and Donaldson invariants when b^+ = 1. I: Cobordisms of moduli spaces and continuity of gluing maps

The present article is the first in a series whose ultimate goal is to prove the Kotschick-Morgan conjecture concerning the wall-crossing formula for the Donaldson invariants of a four-manifold with b + = 1. The conjecture asserts that, in essence, the wall-crossing terms due to changes in the metric depend at most on the homotopy type of the four-manifold and the degree of the invariant. Our principal interest in this conjecture is due to (i) the fact that its proof is expected to resemble that of an important intermediate step towards a proof of Witten's conjecture concerning the relation between Donaldson and Seiberg-Witten invariants [63], using PU(2) monopoles as described in [20], [17], and (ii) it affords us another venue in which to address some of the technical difficulties arising in our work on Witten's conjecture. The additional difficulties in the case of PU(2) monopoles are due to the considerably more complicated gluing theory, the presence of obstructions to deformation and gluing, and the need to consider links of positive-dimensional families of 'reducibles' even in the presence of 'simple type' assumptions. Consequently, it is extremely useful to examine the simpler case of the Kotschick-Morgan conjecture in parallel and separately take into account the difficulties that arise in the case of Witten's conjecture. Witten's conjecture should follow from a final step analogous to Göttsche's computation of the wall-crossing terms, assuming that the Kotschick-Morgan conjecture holds [27]. In this article we present the proof of the first half of a general gluing theorem endowed with several important enhancements not present in previous treatments due to Taubes, Donaldson, and Mrowka. We prove that the Uhlenbeck-compactified moduli spaces of instantons on S 4 for two nearby metrics, which a priori need only be cobordant, are actually homeomorphic and diffeomorphic on smooth strata. We also show that the gluing maps, with obstructions to deformation permitted, extend to maps on the closure of the gluing data which are continuous with respect to the Uhlenbeck topology. The second half of the proof of our general gluing theorem is proved in the sequel [14]. We note that Kronheimer and Mrowka have conjectured a relation between the Yang-Mills and Seiberg-Witten Floer homologies for certain three-manifolds Y [37], [39], [48] and they have a recently announced a program to prove this conjecture using moduli spaces of PU(2) monopoles over cylinders Y × R. One of the difficulties in their program, …
SEM imaging of acoustically stimulated charge transport in solids

Acoustically stimulated charge transport in solids was studied using the scanning electron microscopy method (SEM). The surface acoustic wave on the surface of the YZ-cut of a LiNbO3 crystal was visualized by registration of low-energy secondary electrons in SEM, and the charge distribution on the crystal surface was visualized using the electron beam induced current method. To register the induced current, an interdigital transducer structure was formed from graphene on the crystal surface. It was shown that the charge distribution on the crystal surface corresponds to the distribution of the acoustic wave field on the crystal surface.
What brings people to the social work classroom: a comparative perspective from India and China

ABSTRACT This article explores the motivational factors for students to take up social work as a degree programme at the postgraduate level. The study reports on qualitative interviews (N = 66) conducted with conveniently selected postgraduate social work students at ten different university departments of social work across India and China. The findings revealed that there are (1) gaps in entry to MSW program: need to rethink admission policy; (2) gaps in the impact of studying social work: need to focus on social change and transformation; (3) gaps in career preferences after studying social work: need to focus on career guidance. The result of the study provides information on current international social work developments in education and help policymakers and educators to change or enhance their approaches towards understanding social work theory, teaching practice and student recruitment policies.
Study of fractal features of magnetized plasma through an MHD shell model

A magnetohydrodynamic (MHD) shell model is used to describe the dissipative events which take place in magnetized plasmas. A scatter plot box-counting fractal dimension D is calculated for the time series of the magnetic energy dissipation rate obtained in the MHD shell model, and the correlation between D and the energy dissipation rate is analyzed. We show that, depending on the values of the viscosity and the diffusivity, the fractal dimension and the occurrence of bursts exhibit correlations similar to those observed in previous studies.
Exploring Rotation and Scale Invariant Features in Image Pla- giarism Detection Using Manifold-Ranking Algorithm

Plagiarism, as a crucial offense especially in academia, not only is well-known problem in text but also is becoming widespread in image. In this work, the performance of manifold-ranking, known as robust method among semi-supervised methods, has been investigated by using twelve different features. As its high performance is attributed to the quality of constructed graph, we applied robust k-regular nearest neighbor (k-RNN) graph in the framework of manifold-ranking based retrieval. Among all tested feature point detectors and descriptors, Root-SIFT, the feature point ones, due to it is invariant to an array of image transforms, is the most reliable feature for calculating image similarity. The database consisting of images from scientific papers containing four popular benchmark test images served to test these methods.
Conditions for Stability and Convergence of Set-Valued Stochastic Approximations: Applications to Approximate Value and Fixed point Iterations with Noise

The study of stochastic approximation algorithms (SAAs) with set-valued mean-fields has been popular during recent times due to their applications to many large scale model-free problems arising in stochastic optimization and control. The analysis of such algorithms requires the almost sure boundedness of the iterates, which can be hard to verify. In this paper we extend the ideas of Abounadi, Bertsekas and Borkar involving regular SAAs (with point-to-point maps), to develop easily verifiable sufficient conditions, based on Lyapunov functions, for both stability and convergence of SAAs with set-valued mean-fields. As an important application of our results, we analyze the stochastic approximation counterpart of approximate value iteration (AVI), an important dynamic programming method designed to tackle Bellman's curse of dimensionality. Our framework significantly relaxes the assumptions involved in the analysis of AVI methods. Further, our analysis covers both stochastic shortest path and infinite horizon discounted cost problems. Generalizing further, we present an SAA, together with an analysis of it's stability and convergence for finding fixed points of contractive set-valued maps. To the best of our knowledge ours is the first SAA for finding fixed points of set-valued maps.
A two-sample test with interval censored competing risk data using multiple imputation

Interval censored data frequently occur in observation studies where the subject is followed periodically. In this paper, our interest is to suggest a test statistic to compare the CIF of two groups with interval censored failure time data in the presence of competing risks. Gray (1988) suggested a test statistic for right censored data that motivated a well-known Fine and Gray’s subdistribution hazard model. A multiple imputation technique is adopted to adopt Gray’s test statistic to interval censored data. The powers and sizes of the suggested method are investigated through diverse simulation schemes. The main merit of the suggested method is its simplicity to implement with existing software for right censored data. The method is illustrated by analyzing Bangkok’s HIV cohort dataset.
A torsion balance device for measuring the gravity gradient

Based on the principle of torsion balance measuring gravity gradient, designed a torsion balance gravity gradiometer, consisting of a torsion balance system, an angle measurement system, an amplitude attenuation system, a turntable system, a vacuum container system. considering the stable time of torsion balance suspension system was too long, which had great impacted the efficiency of the gravity gradient measurement, designed an amplitude attenuation system in combination with PID control technology. Simulation results show that, the curvature and horizontal gravity gradient could be measured, the accuracy was as high as 0.5 E(1E = 1 × 10−9m/s2), and the limit efficiency of measuring a group of gravity gradients was better than an hour.
Design of Angle Detection System Based on MPU6050

This paper describes the method of using MPU6050 to detect the dip angle, and designs the hardware circuit. In order to make the detection angle more accurate, the Calman filter algorithm is used in the software programming, which can effective-ly remove the interference and make the measurement precision higher. In the test, the experimental platform is built, which can accurately measure the horizontal angle and vertical angle, this design can be used for the inclination detection of flight control. It has a practical value.