Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA-423-5p Mediates Cocaine-Induced Smooth Muscle Cell Contraction by Targeting Cacna2d2

Background Cocaine abuse increases the risk of atherosclerotic cardiovascular disease (CVD) and causes acute coronary syndromes (ACS) and hypertension (HTN). Significant research has explored the role of the sympathetic nervous system mediating the cocaine effects on the cardiovascular (CV) system. However, the response of the sympathetic nervous system alone is insufficient to completely account for the CV consequences seen in cocaine users. Here, we examined the role of microRNAs (miRNAs) in mediating the effect of cocaine on the CV system. MiRNAs regulate many important biological processes and have been associated with both response to cocaine and CV disease development. Multiple miRNAs have altered expression in the CV system (CVS) upon cocaine exposure. Herein, we examined the role of microRNA-423-5p and the downstream signaling events in regulating cocaine-induced mouse aortic smooth muscle cell (SMC) contraction. Methods To understand the molecular mechanisms underlying the cocaine response in the CV system, we studied the role of miRNA-423-5p and its target Cacna2d2 in the regulation of intracellular calcium concentration and SMC contractility, a critical factor in the modulation of blood pressure (BP). We used in vivo models to evaluate BP and aortic stiffness. Results In vitro, Cocaine treatment decreased miR-423-5p expression and increased Cacna2d2 expression, which led to elevated intracellular calcium concentrations and increased SMC contractility. Overexpression of miR-423-5p, silencing of its target Cacna2d2, and treatment with a calcium channel blocker reversed the elevated SMC contractility caused by cocaine. In contrast, suppression of miR-423-5p increased the intracellular calcium concentration and SMC contractibility. In vivo, overexpression of miR-423-5p ameliorated the increase in BP and aortic stiffness associated with cocaine use. Conclusions MiR-423-5p regulates SMC contraction by modulating Cacna2d2 expression increasing intracellular calcium concentrations. Modulation of miR-423-5p—Cacna2d2—Calcium transport pathway may represent a novel therapeutic strategy to improve cocaine-induced hypertension and aortic stiffness.
Development and optimisation of cationic lipid nanoparticles for mRNA delivery

Messenger RNA (mRNA) has been proposed as a therapeutic agent for various diseases, including cancer. To ensure effective transfection of cancer cells, mRNA needs to be transported with a delivery system that protects its integrity and functionality. In this regard, cationic lipid nanoparticles composed of dioleoylphosphatidylethanolamine (DOPE) and 3β-[N-(N’,N’-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) have emerged as common vectors to deliver mRNA. In this project, we aim to use luciferase mRNA as a reporter to synthesise mRNA-loaded cationic lipid nanoparticles, and optimise their mRNA encapsulation and transfection efficiency in ovarian cancer cells. The optimisation process included: 1) adjusting the lipid formulation; 2) adjusting the input mRNA concentration before lipid nanoparticle extrusion; and 3) adjusting the extrusion methods. After optimisation, the encapsulation efficiency was optimised to 62%, thus achieving a relatively high transfection luminescence signal (9.4 times compared to baseline). The lipid nanoparticles also demonstrated stable physical characteristics and high biocompatibility (above 75% cell viability after treatment) within 24 hours. Overall, this project evaluated the synthesis of DOPE/DC-Chol cationic lipid nanoparticles, and optimised their mRNA encapsulation and transfection efficiency in ovarian cancer cell lines. The optimised lipid nanoparticles can be utilised as an ideal system for mRNA delivery, which could be further developed as a potential platform for the immunotherapy in ovarian cancer.
Conformal scalar fields, isotropic singularities and conformal cyclic cosmologies

We analyse spacetimes with a conformal scalar field source, a cosmological constant and a quartic self-interaction term for the scalar field. We also consider additional matter contents in the form of Maxwell and Yang-Mills fields or radiation fluids. Existence theorems for weakly asymptotically flat spacetimes are given. We give a generalisation of Bekenstein’s result [Ann. Phys. 82, 535 (1974)] and use it to derive existence theorems for spacetimes that contain an isotropic singularity. The results are combined to suggest a mathematical setup for Penrose’s CCC scenario using a conformal scalar field cosmology.
Wnt activity reveals context-specific genetic effects on gene regulation in neural progenitors

Gene regulatory effects in bulk-post mortem brain tissues are undetected at many non-coding brain trait-associated loci. We hypothesized that context-specific genetic variant function during stimulation of a developmental signaling pathway would explain additional regulatory mechanisms. We measured chromatin accessibility and gene expression following activation of the canonical Wnt pathway in primary human neural progenitors from 82 donors. TCF/LEF motifs, brain structure-, and neuropsychiatric disorder-associated variants were enriched within Wnt-responsive regulatory elements (REs). Genetically influenced REs were enriched in genomic regions under positive selection along the human lineage. Stimulation of the Wnt pathway increased the detection of genetically influenced REs/genes by 66.2%/52.7%, and led to the identification of 397 REs primed for effects on gene expression. Context-specific molecular quantitative trait loci increased brain-trait colocalizations by up to 70%, suggesting that genetic variant effects during early neurodevelopmental patterning lead to differences in adult brain and behavioral traits.
Disentangling the neurobiological bases of temporal impulsivity in Huntington's disease

Background Despite its impact on daily life, impulsivity in Huntington’s disease (HD) is understudied as a neuropsychiatric symptom. Our aim is to characterize temporal impulsivity in HD, evaluated through a Delay Discounting (DD) task, and to disentangle the underlying white matter correlates in HD. Methods Forty-seven HD individuals and thirty-six healthy controls conducted a DD task and complementary Sensitivity to Punishment and Sensitivity to Reward (SR) Questionnaire. Diffusion-tensor imaging was employed to characterize the structural connectivity of two limbic tracts: the uncinate fasciculus (UF) and the accumbofrontal tract (NAcc-OFC). Multiple linear regression analyses were applied to analyze the relationship between impulsive behavior and white-matter microstructural integrity. Results Altered structural connectivity in both the NAcc-OFC and UF in HD individuals was observed. Moreover, the variability in structural connectivity of these tracts was associated with the individual differences in temporal impulsivity. Specifically, increased structural connectivity in the right NAcc-OFC predicted increased temporal impulsivity, while reduced connectivity in the left UF was associated with higher temporal impulsivity scores. Limitations Other cognitive mechanisms and white matter tracts may play a role in temporal impulsivity. Conclusions This study provides evidence that individual differences observed in impulsivity may be explained by variability in limbic fronto-striatal tracts. We emphasize the importance of investigating the spectrum of impulsivity in HD, less prevalent than other psychiatric features, but impacting the quality of life of patients and their caregivers.
SEPEM: A tool for statistical modeling the solar energetic particle environment

Solar energetic particle (SEP) events are a serious radiation hazard for spacecraft as well as a severe health risk to humans traveling in space. Indeed, accurate modeling of the SEP environment constitutes a priority requirement for astrophysics and solar system missions and for human exploration in space. The European Space Agency's Solar Energetic Particle Environment Modelling (SEPEM) application server is a World Wide Web interface to a complete set of cross‐calibrated data ranging from 1973 to 2013 as well as new SEP engineering models and tools. Both statistical and physical modeling techniques have been included, in order to cover the environment not only at 1 AU but also in the inner heliosphere ranging from 0.2 AU to 1.6 AU using a newly developed physics‐based shock‐and‐particle model to simulate particle flux profiles of gradual SEP events. With SEPEM, SEP peak flux and integrated fluence statistics can be studied, as well as durations of high SEP flux periods. Furthermore, effects tools are also included to allow calculation of single event upset rate and radiation doses for a variety of engineering scenarios.
Intercellular Communication Compensates Intracellular Proliferative Signal Deficit during Liver Regeneration

It remains to be determined how cells strive to proliferate under proliferative signal deficit. Herein we report that with impaired RTK-Shp2-Ras-Erk signaling, heterogenous hepatocytes formed clusters to divide during liver regeneration. These hepatocytes were characterized by upregulated CD133 while negative for other progenitor cell markers. Pharmaceutical inhibition of proliferative signaling also induced CD133 expression in various cell types, suggesting a common mechanism of stress response. Super-resolution and electron microscopy localized CD133 on intracellular vesicles that apparently migrate between cells. Isolated CD133+ vesicles were enriched with mitogenic mRNAs rather than miRNAs. Single-cell RNA sequencing revealed lower intracellular diversity (entropy) of mitogenic mRNAs in Shp2-deficient cells, which could be remedied by intercellular mRNA exchanges between CD133+ cells. CD133-deficient cells were more sensitive to proliferative signal inhibition in livers and intestinal organoids. These data suggest a mechanism of intercellular communication to offset intracellular signal deficit in hepatocytes and other cell types.
A Non-Canonical IRAK Signaling Pathway Triggered by DNA Damage

Interleukin-1 receptor (IL-1R)-associated kinases (IRAKs) are core effectors of Toll-like receptor (TLR) and IL-1R signaling, with no reported roles outside of innate immunity. We find that vertebrate cells exposed to ionizing radiation (IR) sequentially activate IRAK4 and IRAK1 through a phosphorylation cascade mirroring that induced by TLR/IL-1R, resulting in a potent anti-apoptotic response. However, IR-induced IRAK1 activation does not require the receptors or the IRAK4/1 adaptor protein MyD88, and instead of remaining in the cytoplasm, the activated kinase is immediately transported to the nucleus via a conserved nuclear localization signal. We identify: double-strand DNA breaks (DSBs) as the biologic trigger for this pathway; the E3 ubiquitin ligase Pellino1 as the scaffold enabling IRAK4/1 activation in place of TLR/IL-1R-MyD88; and the pro-apoptotic PIDDosome (PIDD1-RAIDD-caspase-2) as a critical downstream target in the nucleus. The data delineate a non-canonical IRAK signaling pathway derived from, or ancestral to, TLR signaling. This DSB detection pathway, which is also activated by genotoxic chemotherapies, provides multiple actionable targets for overcoming tumor resistance to mainstay cancer treatments.
A Multi-omic and Multi-Species Analysis of Right Ventricular Failure

Right ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no approved treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/proteomic evaluations of RVF are predominately conducted in small animal studies, and data from large animal models are sparse. Moreover, a comparison of the molecular mediators of RVF across species is lacking. Here, we used transcriptomics and proteomics analyses to define the molecular pathways associated with cardiac MRI-derived values of RV hypertrophy, dilation, and dysfunction in pulmonary artery banded (PAB) piglets. Publicly available data from rat monocrotaline-induced RVF and pulmonary arterial hypertension patients with preserved or impaired RV function were used to compare the three species. Transcriptomic and proteomic analyses identified multiple pathways that were associated with RV dysfunction and remodeling in PAB pigs. Surprisingly, disruptions in fatty acid oxidation (FAO) and electron transport chain (ETC) proteins were different across the three species. FAO and ETC proteins and transcripts were mostly downregulated in rats, but were predominately upregulated in PAB pigs, which more closely matched the human data. Thus, the pig PAB metabolic molecular signature was more similar to human RVF than rodents. These data suggest there may be divergent molecular responses of RVF across species, and that pigs more accurately recapitulate the metabolic aspects of human RVF.
Diurnal Land-Sea Rainfall Peak Migration over Sumatera Island, Indonesian Maritime Continent, Observed by TRMM Satellite and Intensive Rawinsonde Soundings

Abstract The diurnal cycle of rainfall and its regional variation over Sumatera Island, Indonesian Maritime Continent, are examined using Tropical Rainfall Measuring Mission (TRMM) satellite precipitation radar (PR) and intensive rawinsonde sounding data. The TRMM PR sensor can detect raindrops directly, regardless of ground and cloud conditions, and can distinguish between convective and stratiform types of rainfall. Rainfall variation over this area was found to have the following characteristics: 1) convective rainfall with a broad peak between 1500 and 2000 LT predominates over the land region of Sumatera Island, whereas rainfall in the early morning, composed almost equally of stratiform and convective types, is predominant over the surrounding sea region. 2) A rainfall peak in the daytime and one in the nighttime migrate with time starting from the southwestern coastline of the island into the inland and offshore regions, respectively. The distance of each rainfall peak migration from the coastline .
Development of NIR Detectors and Science Requirements for SNAP

Development of NIR Detectors and Science Requirments for SNAP by Matthew G. Brown Chair: Gregory Tarlé The SuperNova Acceleration Probe (SNAP) is an optical and near infrared space telescope designed to study the properties of dark energy with multiple techniques. One of SNAP’s primary science goals is to constrain the dark energy equation of state using observations of thousands of type Ia supernovae from a redshift of 0.1−1.7. The highest redshift supernovae provide the most leverage on cosmology measurements since dark energy models, especially those with a time dependent equation of state, begin to diverge at redshifts greater than 1. For objects beyond a redshift of 1, the restframe optical light is shifted to the near infrared (NIR). The SNAP focal plane uses 36 visible CCD detectors and 36 hybridized HgCdTe detectors to achieve accurate measurements of both nearby and high redshift objects over a large field of view. The SNAP NIR detector development effort has succeeded in producing low noise, high quantum efficiency HgCdTe detectors. This work focuses on the characterization and simulation of NIR detectors properties, and the ability of SNAP to constrain the nature of dark energy. Simulations show that recently achieved increases in quantum efficiency lead to the largest gains in accuracy for supernova photometry. The best R&D detectors are approaching the performance of ideal (no noise, QE = 100%) NIR detectors for supernovae observations. Simulated uncertainties for type Ia supernovae are combined with results from cosmic microwave background observations and the SNAP weak lensing survey to constrain the dark energy equation of state. Supernovae alone cannot constrain the nature of dark energy with high accuracy. Independent measurements that have different systematic uncertainties and are sensitive to different combinations of cosmological parameters are needed to achieve the desired precision. With the currently achieved detector technology, the SNAP supernova and weak lensing surveys will constrain σw0 = 0.04 and σwa = 0.14.
Einschreibeverhalten von psychisch Kranken in die integrierte Versorgung einer psychiatrischen Klinik

Zusammenfassung Ziel: Untersucht wurden Faktoren, die das Einschreibeverhalten von Patienten im Rahmen eines Projekts der integrierten Versorgung beeinflussen. Methode: Die Einschreiberaten wurden hinsichtlich Geschlecht und Hauptdiagnose analysiert. Ergebnisse: Die Einschreiberate betrug 59,3 %. Die Diagnose konnte 24,1 % der Variation des Einschreibeverhaltens aufklären, das Geschlecht beeinflusste dieses nicht signifikant. Die höchste Quote zeigten Patienten mit affektiven Störungen, wohingegen Patienten mit einer F2-Diagnose sich nur zu 34,6 % einschrieben. Schlussfolgerungen: Ein Modell mit Einschreibenotwendigkeit ist für die Psychiatrie nur bedingt geeignet.
Radio Observation of Electron Acceleration at Solar Flare Reconnection Outflow Termination Shocks

Using meter-wave solar radio spectral observations of the 2001 September 28 flare, we discuss simultaneously appearing type II-like bursts observed at 40-80 MHz and ≈300 MHz as radio signatures of the upper and lower reconnection outflow termination shock (TS). The features are identified during the impulsive phase but well after the regular traveling-shock type II burst and during the rise of a coronal mass ejection. The upper and lower TS features reveal a tendency for flux anticorrelation over time. We use radio imaging data (Nançay Radio Heliograph) and Yohkoh soft X-ray images to support the TS hypothesis. Assuming shock drift acceleration, we compute the flux of accelerated electrons for lower TS conditions that lead to an electron population with energies of ≈15 keV.
On higher‐order mixed FEM for low Mach number flows: application to a natural convection benchmark problem

We consider higher‐order mixed finite elements with continuous pressures for the computation of stationary compressible flows at low Mach number. The proposed approach is based on a fully coupled treatment of the governing equations and therefore, for steady‐state calculations, does not rely on time‐stepping techniques. The non‐linear problem is solved by means of a quasi‐Newton iteration. The strongly coupled system resulting from higher‐order discretization of the linearized equations requires adequate solvers. We propose a new scheme based on multigrid methods with varying FEM ansatz orders on the grid hierarchy as well as multiplicative smoothers based on blocking techniques. Computational results are described for a benchmark configuration including a flow with heat transfer in the low Mach number regime. Furthermore, the issue of anisotropic grids is addressed in that context. Copyright © 2003 John Wiley & Sons, Ltd.
ON INNER AUTOMORPHISMS AND CENTRAL AUTOMORPHISMS OF NILPOTENT GROUP OF CLASS 2

Let G be a group and let Autc(G) be the group of all central automorphisms of G. Let C* = CAutc(G)(Z(G)) be the set of all central automorphisms of G fixing Z(G) elementwise. In this paper, we prove that if G is a finitely generated nilpotent group of class 2, then C* ≃ Inn(G) if and only if Z(G) is cyclic or Z(G) ≃ Cm × ℤr where has exponent dividing m and r is torsion-free rank of Z(G). Also we prove that if G is a finitely generated group which is not torsion-free, then C* = Inn(G) if and only if G is nilpotent group of class 2 and Z(G) is cyclic or Z(G) ≃ Cm × ℤr where has exponent dividing m and r is torsion-free rank of Z(G). In both cases, we show G has a particularly simple form.
Ice Crystal Linear Growth Rates from −20° to −70°C: Confirmation from Wave Cloud Studies

AbstractAs a result of recent comprehensive laboratory and field studies, many details have been clarified concerning atmospheric ice crystal habits below −20°C as a function of temperature, ice supersaturation, air pressure, and growth history. A predominance of complex shapes has been revealed that is not reflected in most models, with symmetric shapes often incorrectly emphasized. From the laboratory study, linear (maximum dimension), projected area, and volume growth rates of complex and simple habits have been measured under simulated atmospheric conditions for temperatures from −20° to −70°C. Presently, only a few in situ cases of measured ice crystal growth rates are available for comparison with laboratory results. Observations from the Interaction of Aerosol and Cold Clouds (INTACC) field study of a well-characterized wave cloud at −24°C are compared with the laboratory results using a simple method of habit averaging to derive a range of expected growth rates. Laboratory results are also compare.
Lundberg inequalities for renewal equations

Sharp upper and lower bounds are derived for the solution of renewal equations. These include as special cases exponential inequalities, some of which have been derived for specific renewal equations. Together with the well-known Cramér-Lundberg asymptotic estimate, these bounds give additional information about the behaviour of the solution. Nonexponential bounds, which are of use in connection with defective renewal equations, are also obtained. The results are then applied in examples involving the severity of insurance ruin, age-dependent branching processes, and a generalized type II Geiger counter.
Necessary and sufficient conditions for delay-independent stability of linear autonomous systems

Strict quasi-diagonal dominance of the system matrix is known to be sufficient for a linear autonomous system with arbitrary time delays in off-diagonal interactions to be stable. A small perturbation of the matrix yields a perturbed system with the same dominance, and, hence, stability properties. In this paper, it is shown that quasi-diagonal dominance is also necessary for stability with respect to small perturbations and arbitrary off-diagonal time delays. Weaker necessary conditions are given for systems which are themselves stable for all time delays, but which have perturbations that are unstable for certain delays.
Language experience predicts music processing in ½ million speakers of 54 languages

Tonal languages differ from other languages in their use of pitch (tones) to distinguish words. Lifelong experience speaking and hearing tonal languages has been argued to shape auditory processing in ways that generalize beyond the perception of linguistic pitch to the perception of pitch in other domains like music. To examine this, we first conducted a meta-analysis, finding moderate evidence for this idea, but in studies strongly limited by mostly small sample sizes in only a few tonal languages and countries. This makes it challenging to disentangle the effects of linguistic experience from variability in music training experience, cultural differences, and other potential confounds. To address these issues, we used web-based citizen science to test this question on a global scale. We assessed music perception skill in n = 34, 034 native speakers of 19 tonal languages (e.g., Mandarin, Yoruba) and compared their performance to n = 459, 066 native speakers of other languages, including 6 pitch-accented (e.g., Japanese) and 29 non-tonal languages (e.g., Hungarian). Whether or not participants had taken music lessons, native speakers of all 19 tonal languages had an improved ability to discriminate musical melodies. But this improvement came with a trade-off: relative to speakers of pitch-accented or non-tonal languages, tonal language speakers were also worse at processing the musical beat. These results, which held across tonal languages from a variety of geographic regions and were robust to geographic and demographic variation, demonstrate that linguistic experience shapes music perception ability, with implications for relations between music, language, and culture in the human mind.