Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural insight to human Retinoid X receptor alpha-Thyroid hormone receptor beta heterodimer by molecular modelling and MD-simulation studies: role of conserved water molecules

Abstract The Retinoid X receptor alpha–Thyroid hormone receptor beta (RXRα-THRβ) heterodimer plays an important role in physiological function of humans specially in the growth and development. Extensive MD-simulation studies on the aquated complexes of modelled RXRα-THRβ heterodimer with DNA-duplex have indicated the role of some conserved/semiconserved water molecules in the complexation process in presence or absence of Triiodothyronine (T3) and 9-cis retinoic acid (9CR) in the respective Ligand Binding Domain (LBD) domain. Among the seventeen conserved/semi-conserved water molecules, the W1-W4 water centers have been observed to mediate the interaction between the residues of A-chain (DBD of RXR) to consensus sequence (C-chain) of DNA. The W5-W8 water centers involve in recognition of the residues of B-chain (DBD of THR) to C-chain of DNA. The W9-W13 centers have connected the different residues of B-chain (THR) to D-chain of DNA through H-bonds, whereas W14-W17 water molecules were involved in the interaction of A-chain′s (RXR) residues to D-chain of DNA. In our previous study with homodimeric THRβ from Rattus norvegicus we have identified fifteen conserved water molecules at the DNA-DBD interface. Moreover, the conformational flexibility of Met313 (in the LBD of THR) from open to close form in presence or absence of T3 molecule in the holo and Apo-protein may provide a plausible rational on the possible role of that residue to acts as gate which could restrict the solvent molecules to enter into the hydrophobic T3-binding pocket of LBD during the absence of ligand molecule and thus could help the stabilization of that domain in THRβ structure. Communicated by Ramaswamy H. Sarma
Causal continuity in degenerate spacetimes

A change of spatial topology in a causal, compact spacetime cannot occur when the metric is globally Lorentzian. One can however construct a causal metric from a Riemannian metric and a Morse function on the background cobordism manifold, which is Lorentzian almost everywhere except that it is degenerate at each critical point of the function. We investigate causal structure in the neighbourhood of such a degeneracy, when the auxiliary Riemannian metric is taken to be Cartesian ﬂat in appropriate coordinates. For these geometries, we verify Borde and Sorkin’s conjecture that causal discontinuity occurs if and only if the Morse index is 1 or n − 1.
Self Modeling Curve Resolution

This paper presents a method for determining the shapes of two overlapping functions f 1(x) and f 2(x) from an observed set of additive mixtures, [α i f 1(x) + β i f 2(x); i = 1, …, n), of the two functions. This type of problem arises in the fields of spectrophotometry, chromatography, kinetic model building, and many others. The methods described by this paper are based on the use of principal component techniques, and produce two bands of functions, each of which contains one of the unknown, underlying functions. Under certain mild restrictions on the fj (x), each band reduces to a single curve, and the fi (x) are completely determined by the analysis.
Serum Levels of CXCL13 Are Associated With Teriflunomide Response in Patients With Multiple Sclerosis

Background and Objectives To identify biomarkers associated with treatment response in patients with multiple sclerosis (MS) treated with the oral therapies teriflunomide, dimethyl fumarate (DMF), and fingolimod. Methods Serum levels of IL-6, IL-17, TNF-α, granulocyte-macrophage colony-stimulating factor, IL-10, interferon-gamma (IFN-γ) IL-1β, and chemokine ligand 13 (CXCL13) were measured at baseline and 12 months with single molecule array (Simoa) assays in a cohort of patients with MS treated with teriflunomide (N = 19), DMF (N = 22), and fingolimod (N = 25) and classified into “no evidence of disease activity” (NEDA) and EDA patients after 1 year of treatment. Results Serum CXCL13 and TNF-α levels were significantly decreased after treatment with teriflunomide in NEDA compared with EDA patients after 1 year of treatment (p = 0.008 for both cytokines). These findings were validated in an independent cohort of patients with MS treated with teriflunomide (N = 36) and serum CXCL13, and TNF-α levels were again significantly reduced in NEDA patients (p < 0.0001 for CXCL13 and p = 0.003 for TNF-α). CXCL13, but not TNF-α, showed good performance to classify NEDA and EDA patients according to a cut-off value of 9.64 pg/mL based on the change in CXCL13 levels between baseline and 12 months, with a sensitivity of 75% and specificity of 82% in the original cohort, and sensitivity of 65.4% and specificity of 60% in the validation cohort. Discussion Altogether, these results point to CXCL13 as a treatment response biomarker to teriflunomide in relapsing-remitting patients with MS, and the change in CXCL13 levels during the first year of treatment can be used in clinical practice to identify optimal responders to teriflunomide.
Cultural values influencing iTaukei women’s discussion of family planning in the home

Abstract Pacific Sexual and reproductive health is influenced by cultural taboos and sensitivities. Although Pacific values are integral to family planning, open communication in the home is often difficult in the face of changing socio-cultural norms. This study explores the experiences of iTaukei Pacific women living in Fiji and Aotearoa New Zealand, and their discussion of family planning within the family setting. The study utilises talanoa methodology to understand women’s realities and their navigation through shifting sexual and reproductive norms in both countries. The study found that although family may be seen as a place of ‘truth’ in which appropriate, culturally sensitive family planning communication should be available, this was challenged by cultural taboos or tabu which were persistent in family planning discussions. The study calls for greater reliance on holistic approaches to Pacific family planning perspectives and a greater examination of vā or the spaces within which Pacific women’s experiences are negotiated and informed.
Erratum: Evidence of TeV gamma-ray emission from the nearby starburst galaxy NGC 253

Aims. The CANGAROO-II telescope observed sub-TeV gamma-ray emission from the nearby starburst galaxy NGC 253. The emission region was extended with a radial size of 0.3–0.6 degree. On the contrary, HESS could not confirm this emission and gave upper limits at the level of the CANGAROO-II flux. In order to resolve this discrepancy, we analyzed new observational results for NGC 253 by CANGAROO-III and also assessed the results by CANGAROO-II. Methods. Observation was made with three telescopes of the CANGAROO-III in October 2004. We analyzed three-fold coincidence data by the robust Fisher Discriminant method to discriminate gamma ray events from hadron events. Results. The result by the CANGAROO-III was negative. The upper limit of gamma ray flux was 5.8% Crab at 0.58 TeV for pointsource assumption. In addition, the significance of the excess flux of gamma-rays by the CANGAROO-II was lowered to less than 4 sigma after assessing treatment of malfunction of photomultiplier tubes.
One-Year Outcomes in Anticoagulated Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention: Insights From the Greek Antiplatelet Atrial Fibrillation Registry

Abstract: GReek-AntiPlatElet Atrial Fibrillation registry is a multicenter, observational, noninterventional study of atrial fibrillation patients undergoing percutaneous coronary intervention. Primary endpoint included clinically significant bleeding rate at 12 months between different antithrombotic regimens prescribed at discharge; secondary endpoints included major adverse cardiovascular events and net adverse clinical events. A total of 647 patients were analyzed. Most (92.9%) were discharged on novel oral anticoagulants with only 7.1% receiving the vitamin K antagonist. A little over half of patients (50.4%) received triple antithrombotic therapy (TAT)—mostly (62.9%) for ≤1 month—whereas the rest (49.6%) received dual antithrombotic therapy (DAT). Clinically significant bleeding risk was similar between TAT and DAT [Hazard ratio (HR) = 1.08; 95% confidence interval (CI), 0.66–1.78], although among TAT-receiving patients, the risk was lower in those receiving TAT for ≤1 month (HR = 0.50; 95% CI, 0.25–0.99). Anticoagulant choice (novel oral anticoagulant vs. vitamin K antagonist) did not significantly affect bleeding rates (P = 0.258). Age, heart failure, leukemia/myelodysplasia, and acute coronary syndrome were associated with increased bleeding rates. Risk of major adverse cardiovascular events and net adverse clinical events was similar between ΤAT and DAT (HR = 1.73; 95% CI, 0.95–3.18, P = 0.075 and HR = 1.39; 95% CI, 0.93–2.08, P = 0.106, respectively). In conclusion, clinically significant bleeding and ischemic rates were similar between DAT and TAT, although TAT >1 month was associated with higher bleeding risk.
Enhanced production of acetyl-CoA-based products via peroxisomal surface display in Saccharomyces cerevisiae

Significance Colocalization of pathway enzymes is a proven method to increase pathway flux and the synthesis of nonnative products. Here we detail a method of colocalization that both uses the peroxisomal membrane surface as an anchoring site and enables capture of peroxisomal acetyl-CoA. Display of the native peroxisomal/mitochondrial enzyme Cat2, to intercept exported acetyl-carnitine for conversion back to acetyl-CoA at the membrane surface, significantly increased acetyl-CoA levels. The production of a polyketide (using three peroxisome-bound pathway enzymes) also increased, demonstrating the effectiveness of this display strategy for both colocalization and accessing peroxisomal acetyl-CoA. This method can be used to colocalize any small pathway, and with the anchoring of Cat2, can be applied to increase the synthesis of other acetyl-CoA-based products.
Cognitive and Developmental Functions in Autistic and Non-Autistic Children and Adolescents: Evidence from the Intelligence and Development Scales–2

Autistic individuals often show impairments in cognitive and developmental domains beyond the core symptoms of lower social communication skills and restricted repetitive behaviors. Consequently, the assessment of cognitive and developmental functions constitutes an essential part of the diagnostic evaluation. Yet, evidence on differential validity from intelligence and developmental tests, which are commonly used with autistic individuals, varies widely. In the current study, we investigated the cognitive (i.e., intelligence, executive functions) and developmental (i.e., psychomotor skills, social–emotional skills, basic skills, motivation and attitude, participation during testing) functions of autistic and non-autistic children and adolescents using the Intelligence and Development Scales–2 (IDS-2). We compared 43 autistic (Mage = 12.30 years) with 43 non-autistic (Mage = 12.51 years) participants who were matched for age, sex, and maternal education. Autistic participants showed significantly lower mean values in psychomotor skills, language skills, and the evaluation of participation during testing of the developmental functions compared to the control sample. Our findings highlight that autistic individuals show impairments particularly in motor and language skills using the IDS-2, which therefore merit consideration in autism treatment in addition to the core symptoms and the individuals’ intellectual functioning. Moreover, our findings indicate that particularly motor skills might be rather neglected in autism diagnosis and may be worthy of receiving more attention. Nonsignificant group differences in social–emotional skills could have been due to compensatory effects of average cognitive abilities in our autistic sample.
Weighted summation and contrast normalization account for short-latency disparity vergence responses to white noise stimuli in humans

Natural images are typically broadband, whereas detectors in early visual processing are selective for narrow ranges of spatial frequency. White noise patterns are widely used in laboratory settings to investigate how responses are derived from Fourier components in the image. Here, we report disparity vergence responses (DVRs) to white noise stimuli in human subjects and compare these with responses to white noise patterns filtered with bandpass filters and notch filters and to sinusoidal gratings. Although the contribution of these short-latency eye movements to the overall vergence response to a given stimulus is generally small, they have proven to be a valuable tool for the study of the early mechanisms that process disparity stimuli in human subjects. Removing lower spatial frequency (SF) components reduced DVR amplitude, whereas removing higher SF components led to an increase in DVR amplitude. For larger disparities, the transition occurred at lower SFs. All of these effects were quantitatively well described by a model that combined two factors: (a) an excitatory drive determined by a weighted sum of stimulus Fourier components, which was scaled by (b) a contrast normalization mechanism.
Euglena International Network (EIN): Driving euglenoid biotechnology for the benefit of a challenged world

ABSTRACT Euglenoids (Euglenida) are unicellular flagellates possessing exceptionally wide geographical and ecological distribution. Euglenoids combine a biotechnological potential with a unique position in the eukaryotic tree of life. In large part these microbes owe this success to diverse genetics including secondary endosymbiosis and likely additional sources of genes. Multiple euglenoid species have translational applications and show great promise in production of biofuels, nutraceuticals, bioremediation, cancer treatments and more exotically as robotics design simulators. An absence of reference genomes currently limits these applications, including development of efficient tools for identification of critical factors in regulation, growth or optimization of metabolic pathways. The Euglena International Network (EIN) seeks to provide a forum to overcome these challenges. EIN has agreed specific goals, mobilized scientists, established a clear roadmap (Grand Challenges), connected academic and industry stakeholders and is currently formulating policy and partnership principles to propel these efforts in a coordinated and efficient manner.
Scalar field dark matter: Nonspherical collapse and late-time behavior

Instituto de F´isica y Matem´aticas, Universidad Michoacana de San Nicol´as de Hidalgo. Ediﬁcio C-3,Cd. Universitaria, A. P. 2-82, 58040 Morelia, Michoac´an, M´exico. (Dated: February 5, 2008)We show the evolution of non-spherically symmetric balls of a self-gravitating scalar ﬁeld in theNewtonian regime or equivalently an ideal self-gravitating condensed Bose gas. In order to do so,we use a ﬁnite diﬀerencing approximation of the Shcr¨odinger-Poisson (SP) system of equationswith axial symmetry in cylindrical coordinates. Our results indicate: 1) that spherically symmetricground state equilibrium conﬁgurations are stable against non-spherical perturbations and 2) thatsuch conﬁgurations of the SP system are late-time attractors for non-spherically symmetric initialproﬁles of the scalar ﬁeld, which is a generalization of such behavior for spherically symmetric initialproﬁles. Our system and the boundary conditions used, work as a model of scalar ﬁeld dark mattercollapse after the turnaround point. In such case, we have found that the scalar ﬁeld overdensitiestolerate non-spherical contributions to the proﬁle of the initial ﬂuctuation.
Mass Transfer from Mobile to Immobile Regions in Irregularly Shaped Micro‐Channels at Low Reynolds Number

Transient mass transfer in rough‐walled micro‐channels was investigated experimentally. We conducted experiments using rough‐walled channels with various irregularities at small Reynolds number conditions. Mass transfer in the mainstream (mobile region) and dead water region (immobile region) were quantified using an image analysis technique based on absorption photometry. The experimental results showed that the solute dispersion in the mobile region was influenced by the irregular shape of the channel wall complicatedly. In contrast, mass transfer in the immobile region occurred by molecular diffusion independently on the wall roughness in our experimental conditions. The irregular shape of channel wall may enhance the mass transfer in mobile region by distorting the velocity distribution (Togi et al., 2020), while the solute redistribution to immobile region may suppress it in streamwise direction, just on a longer time scale. We developed a mass transfer model analogous to Mobile‐Immobile model (MIM model) proposed by previous studies. The concept of the model is the same as the previous study (Zhou et al., 2019) and the coefficients of the model describing mass transfer in each region were quantified from the experimental results as functions of geometric characteristics of the rough‐walled channel. In addition, mass transfer coefficient from mobile to immobile regions were derived mathematically based on the experimental results. The MIM model with the coefficients derived in this study well describes solute dispersion in variously shaped irregular channels quantitatively.
Artificial pancreas systems: experiences from concept to commercialisation

ABSTRACT Introduction Automated insulin delivery (AID) systems, known as artificial pancreas or closed-loop glucose control systems, have been developed to improve the glycemic outcomes of people with type 1 diabetes. These systems use a control algorithm that automatically modifies the amount of insulin infused into a patient based on real-time blood glucose measurements. This study presents a summary of key clinical and technical issues related to the development of the first commercial AID systems and their evolution into commercial biomedical devices. Areas covered Highlights of each AID system are summarized through timelines, ranging from the definition of the core strategy of the control algorithm to the practical application and subsequent commercial approval. Tabulated information regarding the conducted main clinical studies is also presented. Expert opinion Insulin therapy has evolved up to the current commercial AID systems available, which have provided patients access to a safer and more effective therapy owing to automatic adjustments to insulin. However, this technology is relatively new and can be significantly improved. Limitations include the resistance of healthcare providers, high costs, and the availability of this treatment. The future of this technology is directed toward obtaining fully automatic control systems.
Distinct populations of eosinophils in the human thymus with capacity to modulate thymocyte maturation

Local differentiation of eosinophil precursors occurs in the human thymus. Thymic eosinophils are often positioned in the corticomedullary junction between the CD4+CD8+ double‐positive (DP) thymocytes and the CD4+ or CD8+ single‐positive (SP) thymocytes. The aims of this study were to (1) determine if there are distinct thymic eosinophil populations that differ from the blood eosinophil populations and (2) evaluate the capacity of thymic eosinophils to promote the development of SP thymocytes from DP thymocytes. Thymic and blood eosinophils from thymectomized infants (n = 7) were compared regarding the expression of 34 molecules using cytometry by time‐of‐flight (CyTOF). In addition, FACS‐sorted thymic eosinophils were co‐cultured with autologous CD3/CD28‐stimulated DP, CD4 SP, and CD8 SP thymocytes and analysed by flow cytometry and CyTOF. X‐shift clustering analysis and viSNE dimensionality reduction were performed. Seven eosinophil populations were identified within the blood and thymus, respectively, five of which were specific for either tissue. Whereas the blood eosinophil populations varied between individuals, the thymic eosinophil populations were more uniform. The eosinophil‐thymocyte co‐cultures resulted in (1) an increase in CD4 SP thymocytes when eosinophils were cultured with DP thymocytes, (2) decreased frequency of CD8 SP thymocytes when these were cultured with eosinophils, and (3) a more mature thymic phenotype when eosinophils were cultured with CD4 SP thymocytes. Thymic eosinophils are a specialized population of eosinophils with a distinct phenotype that separates them from their blood counterparts, and in vitro they appear to favour CD4 SP thymocyte development to the detriment of CD8 SP thymocytes.
FIRST-2Mass Sources below the APM Detection Threshold: A Population of Highly Reddened Quasars

We have constructed a sample of bright near-infrared sources that are detected at radio wavelengths but undetected on the first-generation Palomar Observatory Sky Survey (POSSI) plates in order to search for a population of dust-obscured quasars. Optical and infrared spectroscopic follow-up of the sample has led to the discovery of 17 heavily reddened quasars (B-K > 6.5), 14 of which are reported here for the first time. This has allowed us to define a region in the R-K, J-K color plane in which 50% of the radio-selected objects are highly reddened quasars. We compare the surface density of this previously overlooked population to that of ultraviolet-excess radio-selected quasars, finding that they make up ~20% of the total quasar population for K ≲ 15.5.
Nonperturbative behavior of the quantum phase transition to a nematic Fermi fluid

We discuss shape (Pomeranchuk) instabilities of the Fermi surface of a two-dimensional Fermi system using bosonization. We consider in detail the quantum critical behavior of the transition of a two-dimensional Fermi fluid to a nematic state which breaks spontaneously the rotational invariance of the Fermi liquid. We show that higher dimensional bosonization reproduces the quantum critical behavior expected from the Hertz-Millis analysis, and verify that this theory has dynamic critical exponent $z=3$. Going beyond this framework, we study the behavior of the fermion degrees of freedom directly, and show that at quantum criticality as well as in the quantum nematic phase (except along a set of measure zero of symmetry-dictated directions) the quasiparticles of the normal Fermi liquid are generally wiped out. Instead, they exhibit short-ranged spatial correlations that decay faster than any power law, with the law $\ensuremath{\mid}x{\ensuremath{\mid}}^{\ensuremath{-}1}\mathrm{exp}(\ensuremath{-}\mathrm{const}\phantom{\rule{0.3em}{0ex}}\ensuremath{\mid}x{\ensuremath{\mid}}^{1∕3})$ and we verify explicitly the vanishing of the fermion residue utilizing this expression. In contrast, the fermion autocorrelation function has the behavior $\ensuremath{\mid}t{\ensuremath{\mid}}^{\ensuremath{-}1}\mathrm{exp}(\ensuremath{-}\mathrm{const}\phantom{\rule{0.3em}{0ex}}\ensuremath{\mid}t{\ensuremath{\mid}}^{\ensuremath{-}2∕3})$. In this regime we also find that, at low frequency, the single-particle fermion density of states behaves as ${N}^{*}(\ensuremath{\omega})={N}^{*}(0)+B{\ensuremath{\omega}}^{2∕3}\mathrm{ln}\ensuremath{\omega}+\ensuremath{\cdots}$, where ${N}^{*}(0)$ is larger than the free Fermi value, $N(0)$, and $B$ is a constant. These results confirm the non-Fermi liquid nature of both the quantum critical theory and of the nematic phase.