Miracle-dz/UniFAR-FTUs huggingface dataset:
High mobility group box 1 protein regulates osteoclastogenesis through direct actions on osteocytes and osteoclasts in vitro

Old age and Cx43 deletion in osteocytes are associated with increased osteocyte apoptosis and osteoclastogenesis. We previously demonstrated that apoptotic osteocytes release elevated concentrations of the proinflammatory cytokine, high mobility group box 1 protein (HMGB1) and apoptotic osteocyte conditioned media (CM) promotes osteoclast differentiation. Further, prevention of osteocyte apoptosis blocks osteoclast differentiation and attenuates the extracellular release of HMGB1 and RANKL. Moreover, sequestration of HMGB1, in turn, reduces RANKL production/release by MLO‐Y4 osteocytic cells silenced for Cx43 (Cx43def), highlighting the possibility that HMGB1 promotes apoptotic osteocyte‐induced osteoclastogenesis. However, the role of HMGB1 signaling in osteocytes has not been well studied. Further, the mechanisms underlying its release and the receptor(s) responsible for its actions is not clear. We now report that a neutralizing HMGB1 antibody reduces osteoclast formation in RANKL/M‐CSF treated bone marrow cells. In bone marrow macrophages (BMMs), toll‐like receptor 4 (TLR4) inhibition with LPS‐RS, but not receptor for advanced glycation end products (RAGE) inhibition with Azeliragon attenuated osteoclast differentiation. Further, inhibition of RAGE but not of TLR4 in osteoclast precursors reduced osteoclast number, suggesting that HGMB1 produced by osteoclasts directly affects differentiation by activating TLR4 in BMMs and RAGE in preosteoclasts. Our findings also suggest that increased osteoclastogenesis induced by apoptotic osteocytes CM is not mediated through HMGB1/RAGE activation and that direct HMGB1 actions in osteocytes stimulate pro‐osteoclastogenic signal release from Cx43def osteocytes. Based on these findings, we propose that HMGB1 exerts dual effects on osteoclasts, directly by inducing differentiation through TLR4 and RAGE activation and indirectly by increasing pro‐osteoclastogenic cytokine secretion from osteocytes.
High throughput sequencing reveals Drosophila suzukii responses to insecticides

Global climate change and acquired resistance to insecticides are threats to world food security. Drosophila suzukii, a devastating invasive pest in many parts of the world, causes substantial economic losses to fruit production industries, forcing farmers to apply broad‐spectrum insecticides frequently. This could lead to the development of insecticide resistance. We determined the Lethal Concentration 50 (median lethal concentration, LC50) values of zeta‐cypermethrin, spinosad, and malathion insecticides against D. suzukii colonies established from Clarke and Pierce county Georgia, United States. The LC50 values were 3 fold higher in the Pierce county population for all insecticide treatments. We then used RNA sequencing to analyze the responses of Pierce and Clarke population flies surviving a LC50 treatment of the 3 insecticides. We identified a high number of differentially expressed genes that are likely involved in detoxification and reduced cuticular penetration, especially in the Pierce population, with extensive overlap in differentially expressed genes between the 3 insecticide treatments. Finally, we predicted fewer nonsynonymous single nucleotide variants having deleterious effects on protein function among detoxification, insecticide target, and cuticular protein encoding genes in Pierce flies. Thus a combination of increased gene expression and fewer deleterious single nucleotide variants highlights molecular mechanisms underlying the higher LC50 values for Pierce population flies.
Decoding signatures of extra dimensions and estimating spin of quasars from the continuum spectrum

Continuum spectrum emitted by the accretion disk around quasars hold a wealth of information regarding the strong gravitational field produced by the massive central object. Such strong gravity regime is often expected to exhibit deviations from general relativity (GR) which may manifest through the presence of extra dimensions. Higher dimensions, which serve as the corner stone for string theory and M-theory can act as promising alternatives to dark matter and dark energy with interesting implications in inflationary cosmology, gravitational waves and collider physics. Therefore it is instructive to investigate the effect of more than four spacetime dimensions on the black hole continuum spectrum which provide an effective astrophysical probe to the strong gravity regime. To explore such a scenario, we compute the optical luminosity emitted by a thin accretion disk around a rotating supermassive black hole albeit in the presence of extra dimensions. The background metric resembles the Kerr-Newman spacetime in GR where the tidal charge parameter inherited from extra dimensions can also assume negative signature. The theoretical luminosity computed in such a background is contrasted with optical observations of eighty quasars. The difference between the theoretical and observed luminosity for these quasars is used to infer the most favoured choice of the rotation parameter for each quasar and the tidal charge parameter. This has been achieved by minimizing/maximizing several error estimators, e.g., chi-squared, Nash-Sutcliffe efficiency, index of agreement etc. Intriguingly, all of them favour a negative value for the tidal charge parameter, a characteristic signature of extra dimensions. Thus accretion disk does provide a significant possibility of exploring the existence of extra dimensions through its close correspondence with the strong gravity regime.
Regulatory T cells: the future of autoimmune disease treatment

ABSTRACT Introduction: CD4 + T regulatory cells (Tregs) have been described as the most potent immunosuppressive cells in the human body. They have been found to control autoimmunity, and clinical attempts have been made to apply them to treat autoimmune diseases. Some specific pathways utilized by Tregs in the regulation of immune response or Tregs directly as cellular products are tested in the clinic. Areas covered: Here, we present recent advances in the research on the biology and clinical applications of Tregs in the treatment of autoimmune diseases. Expert opinion: Regulatory T cells seem to be a promising tool for the treatment of autoimmune diseases. The development of both cell-based therapies and modern pharmacotherapies which affect Tregs may strongly improve the treatment of autoimmune disorders. Growing knowledge about Treg biology together with the latest biotechnology tools may give an opportunity for personalized therapies in these conditions.
Clinical impact of absolute lymphocyte count on day 30 after unmanipulated haploidentical blood and marrow transplantation for pediatric patients with hematological malignancies

Currently, limited information is available regarding the effects of early lymphocyte recovery on transplant outcomes in pediatric patients with hematological malignancies after unmanipulated haploidentical transplantation. In this study, we evaluated the association of Day 30 absolute lymphocyte count (ALC-30) with transplant outcomes in 60 consecutive pediatric patients with hematological malignancies receiving T-cell-repleted transplantation from an haploidentical related donors. After median follow-up of 36 months (range, 1.4-75 months), higher relapse rate was observed in patients with an ALC-30 < 300 cells/μL compared to patients with an ALC-30 ≥ 300 cells/μL (35.5% vs. 13.8%, P = 0.049). More patients died of infections in those with an ALC-30 < 300 cells/μL compared with patients with an ALC-30 ≥ 300 cells/μL (25.8% vs. 3.4%, P = 0.015). The ALC-30 above the cutoff value 300 cells/μL was associated with improved overall-survival (HR 0.301, 95% CI 0.117-0.771; P = 0.012), leukemia free survival (HR 0.195, 95% CI 0.078-0.498; P=0.002), less relapse (HR 0.224 95% CI 0.070-0.717; P = 0.012), and less transplant- related mortality (HR=0.166; 95%CI 0.037-0.750; P = 0.020). Our results suggest that a higher ALC-30 ≥ 300 cells/μL) could be a useful and simple tool to predict pediatric patients with a superior outcome after unmanipulated haploidentical transplantation.
TASI lectures on Future Colliders

These lectures review the main motivations for future high-energy colliders, focusing on the understanding of electroweak symmetry breaking and on the search for physics beyond the Standard Model. The open questions and the challenges are common to all future projects; for concreteness, I will use studies of the potential of $\rm e^+e^-$ and pp circular colliders to provide examples of the anticipated physics reach.
p-Akt as a potential poor prognostic factor for gastric cancer: a systematic review and meta-analysis

To understand the relationship between p-Akt expression and the prognosis of patients with gastric cancer, we searched six databases, Pubmed, EMBASE, Cochrane Library, CNKI, Wanfang and CBM for relevant articles in order to conduct this metaanalysis. The pooled hazard ratios and corresponding 95%CI of overall survival were calculated to evaluate the prognostic value of p-Akt expression in patients with gastric cancer. With 2261 patients combined from 13 available studies, the pooled HR showed a poor prognosis in patients with gastric cancer in the univariate analysis (HR=1.88, 95%CI:1.45-2.43, P<0.00001), and the group “univariate analysis+estimate” (HR=1.41, 95%CI: 1.01-1.97, P=0.04), but not in multivariate analysis (HR=0.66, 95%CI: 0.29-1.52, P=0.33) and estimate (HR=1.13, 95%CI: 0.65-1.95, P=0.67). In conclusion, our results indicated that p-Akt was likely to be an indicator of poor prognosis in patients with gastric cancer.
Does a Disadvantaged Candidate Choose an Extremist Position

Does a disadvantaged candidate always choose an extremist program? When does a less competent candidate have an incentive to move to extreme positions in order to differentiate himself from the more competent candidate? Recent work answers by the affirmative - Groseclose (1999), Ansolabehere and Snyder (2000), Aragones and Palfrey (2002), (2003). We consider a two-candidates electoral competition over public consumption, with a two-dimensional policy space and two dimensions of candidate heterogeneity. In this setting, we show that the conclusion depends on the relative competences of candidates and distinguish between two types of advantages (an absolute advantage and comparative advantage in providing the two public goods).
Respiratory symptoms and home environment in children: a national survey

BACKGROUND Respiratory diseases are common in childhood and may lead to chronic disease in adult life; environmental factors probably play an important part in their causation. METHODS A survey of respiratory symptoms in children aged 12–14 years was conducted throughout Great Britain as part of the International Study of Asthma and Allergies in Childhood (ISAAC). Information was obtained on certain aspects of the home environment in order to assess their importance as risk factors. RESULTS The response rate was 79.3%, and 25 393 children in 93 schools participated. In a multiple regression analysis, wheeze was reported more often in non-metropolitan areas and in association with active smoking, passive smoking, the presence of a furry pet, bottled gas, paraffin, and other unusual heating fuels; small regional differences persisted. Current smoking, previous smoking, and passive smoking accounted for 10.4%, 6.8%, and 6.5%, respectively, of wheezing in the past 12 months, and furry pets accounted for 5.0%. Cough and phlegm were associated with active and passive smoking and with the miscellaneous fuels; similar associations were found for rhinitis, but were less consistent for rhinitis occurring in spring and summer. Gas cooking showed little association with respiratory symptoms. CONCLUSIONS Passive as well as active smoking is an important cause of respiratory symptoms in adolescence. Pets seem to increase the risk of wheeze and rhinitis, and fumes from certain unusual heating fuels may have adverse effects. Home environment and geographical location have independent effects on the prevalence of respiratory symptoms.
Optimal recovery of a radiating source with multiple frequencies along one line

We study an inverse problem where an unknown radiating source is observed with collimated detectors along a single line and the medium has a known attenuation. The research is motivated by applications in SPECT and beam hardening. If measurements are carried out with frequencies ranging in an open set, we show that the source density is uniquely determined by these measurements up to averaging over levelsets of the integrated attenuation. This leads to a generalized Laplace transform. We also discuss some numerical approaches and demonstrate the results with several examples.
Radiative Transfer in Half Spaces of Arbitrary Dimension

Abstract We solve the classic albedo and Milne problems of plane-parallel illumination of an isotropically-scattering half-space when generalized to a Euclidean domain for arbitrary A continuous family of pseudo-problems and related H functions arises and includes the classical 3D solutions, as well as 2D “Flatland” and rod-model solutions, as special cases. The Case-style eigenmode method is applied to the general problem and the internal scalar densities, emerging distributions, and their respective moments are expressed in closed-form. Universal properties invariant to dimension d are highlighted and we find that a discrete diffusion mode is not universal for d > 3 in absorbing media. We also find unexpected correspondences between differing dimensions and between anisotropic 3D scattering and isotropic scattering in high dimension.
Patient sex and success of peripheral percutaneous transluminal arterial angioplasty.

HYPOTHESIS Female sex negatively affects the durability of percutaneous angioplasty of native arteries supplying the lower extremity. DESIGN Outcome analysis of the results of percutaneous angioplasty of lower extremity arteries in a single vascular surgery practice. SETTING University-affiliated community hospital. PATIENTS All patients undergoing percutaneous intervention on lower extremity arteries during 10 years. INTERVENTIONS Indication for intervention, anatomic site of intervention, placement of percutaneous stents, and length of lesion undergoing angioplasty were noted. Patient demographics and risk factors were identified. MAIN OUTCOME MEASURES Results were analyzed by sex. Kaplan-Meier life tables were plotted and differences between groups tested by the log-rank method. A Cox proportional hazards regression model was used to perform the multivariate analysis. RESULTS During 10 years, 351 angioplasties were performed in 248 patients, 173 in women and 178 in men. There was no difference between men and women in indication for intervention, length and type of lesion treated, or quality of distal runoff. Univariate survival analysis identified a difference in duration of patency between men and women (P = .047). However, multivariate analysis demonstrated no significant difference in duration of patency between men and women (P = .18). Iliac angioplasty and adequate distal runoff were positive predictors of long-term patency (P<.001 for both). CONCLUSIONS There appears to be no significant difference in the durability of angioplasty between men and women. However, location of angioplasty and adequacy of distal runoff may be useful in determining when to use angioplasty.
Interval estimators for ratios of independent quantiles and interquantile ranges

Abstract Recent research has shown that interval estimators with good coverage properties are achievable for some functions of quantiles, even when sample sizes are not large. Motivated by this, we consider interval estimators for the ratios of independent quantiles and interquantile ranges that will be useful when comparing location and scale for two samples. Simulations show that the intervals have excellent coverage properties for a wide range of distributions, including those that are heavily skewed. Examples are also considered that highlight the usefulness of using these approaches to compare location and scale.
Sex differences in pre-diagnosis concerns for children later diagnosed with autism spectrum disorder

In the absence of intellectual impairment, girls are diagnosed with autism spectrum disorder significantly less and later than boys. This study explored potential reasons for why autism spectrum disorder may be more difficult to identify in girls, based on carer concerns during the pre-diagnosis period. Carers of 92 boys and 60 girls diagnosed with autism spectrum disorder from school age completed an online survey addressing concerns regarding the child’s development during the pre-school years (pre-diagnosis). Significant sex differences were evident in key early concerns, as well as the strategies used to navigate pre-school social situations, and the types of restricted interests. Findings suggest, from carer perspective, that girls who went on to be diagnosed with autism spectrum disorder presented differently when compared to boys, providing insight into why the diagnosis of autism spectrum disorder may be more difficult to make with cognitively able girls.
Weighted Sum-Rate Optimization for Intelligent Reflecting Surface Enhanced Wireless Networks.

Intelligent reflecting surface (IRS) is a promising solution to build a programmable wireless environment for future communication systems. In practice, an IRS consists of massive low-cost elements, which can steer the incident signal in fully customizable ways by passive beamforming. In this paper, we consider an IRS-aided multiuser multiple-input single-output (MISO) downlink communication system. In particular, the weighted sum-rate of all users is maximized by joint optimizing the active beamforming at the base-station (BS) and the passive beamforming at the IRS. In addition, we consider a practical IRS assumption, in which the passive elements can only shift the incident signal to discrete phase levels. This non-convex problem is firstly decoupled via Lagrangian dual transform, and then the active and passive beamforming can be optimized alternatingly. The active beamforming at BS is optimized based on the fractional programming method. Then, three efficient algorithms with closed-form expressions are proposed for the passive beamforming at IRS. Simulation results have verified the effectiveness of the proposed algorithms as compared to different benchmark schemes.
Analytical steady-state solutions for pressure with a multiscale non-local model for two-fluid systems

We consider the nonlocal multiscale model for surface tension \citep{Tartakovsky2018} as an alternative to the (macroscale) Young-Laplace law. The nonlocal model is obtained in the form of an integral of a molecular-force-like function with support $\varepsilon$ added to the Navier-Stokes momentum conservation equation. Using this model, we calculate analytical forms for the steady-state equilibrium pressure gradient and pressure profile for circular and spherical bubbles and flat interfaces in two and three dimensions. According to the analytical solutions, the pressure changes continuously across the interface in a way that is quantitatively similar to what is observed in MD simulations. Furthermore, the pressure difference $P_{\varepsilon, in} - P_{\varepsilon, out}$ satisfies the Young-Laplace law for the radius of curvature greater than $3\varepsilon$ and deviates from the Young-Laplace law otherwise (i.e., $P_{\varepsilon, in} - P_{\varepsilon, out}$ goes to zero as the radius of the curvature goes to zero, where $P_{\varepsilon, out}$ is the pressure outside of the bubble at the distance greater than $3\varepsilon$ from the interface and $P_{\varepsilon, in}$ is the pressure at the center of the bubble). The latter indicates that the surface tension in the proposed model decreases with the decreasing radius of curvature, which agrees with molecular dynamics simulations and laboratory experiments with nanobubbles. Therefore, our results demonstrate that the nonlocal model behaves microscopically at scales smaller than $\varepsilon$ and macroscopically, otherwise.
Association of Parent Training With Child Language Development: A Systematic Review and Meta-analysis.

Importance Training parents to implement strategies to support child language development is crucial to support long-term outcomes, given that as many as 2 of 5 children younger than 5 years have difficulty learning language. Objective To examine the association between parent training and language and communication outcomes in young children. Data Sources Searches of ERIC, Academic Search Complete, PsycINFO, and PsycARTICLES were conducted on August 11, 2014; August 18, 2016; January 23, 2018; and October 30, 2018. Study Selection Studies included in this review and meta-analysis were randomized or nonrandomized clinical trials that evaluated a language intervention that included parent training with children with a mean age of less than 6 years. Studies were excluded if the parent was not the primary implementer of the intervention, the study included fewer than 10 participants, or the study did not report outcomes related to language or communication. Data Extraction and Synthesis Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were applied to a total of 31 778 articles identified for screening, with the full text of 723 articles reviewed and 76 total studies ultimately included. Main Outcomes and Measures Main outcomes included language and communication skills in children with primary or secondary language impairment and children at risk for language impairment. Results This meta-analysis included 59 randomized clinical trials and 17 nonrandomized clinical trials including 5848 total participants (36.4 female [20.8%]; mean [SD] age, 3.5 [3.9] years). The intervention approach in 63 studies was a naturalistic teaching approach, and 16 studies used a primarily dialogic reading approach. There was a significant moderate association between parent training and child communication, engagement, and language outcomes (mean [SE] Hedges g, -0.33 [0.06]; P < .001). The association between parent training and parent use of language support strategies was large (mean [SE] Hedges g, 0.55 [0.11], P < .001). Children with developmental language disorder had the largest social communication outcomes (mean [SE] Hedges g, 0.37 [0.17]); large and significant associations were observed for receptive (mean [SE] Hedges g, 0.92 [0.30]) and expressive language (mean [SE] Hedges g, 0.83 [0.20]). Children at risk for language impairments had moderate effect sizes across receptive language (mean [SE] Hedges g, 0.28 [0.15]) and engagement outcomes (mean [SE] Hedges g, 0.36 [0.17]). Conclusions and Relevance The findings suggest that training parents to implement language and communication intervention techniques is associated with improved outcomes for children and increased parent use of support strategies. These findings may have direct implications on intervention and prevention.