Modeling Progressive Fibrosis with Pluripotent Stem Cells Identifies an Anti-fibrotic Small Molecule.

Progressive organ fibrosis accounts for one-third of all deaths worldwide, yet preclinical models that mimic the complex, progressive nature of the disease are lacking, and hence, there are no curative therapies. Progressive fibrosis across organs shares common cellular and molecular pathways involving chronic injury, inflammation, and aberrant repair resulting in deposition of extracellular matrix, organ remodeling, and ultimately organ failure. We describe the generation and characterization of an in vitro progressive fibrosis model that uses cell types derived from induced pluripotent stem cells. Our model produces endogenous activated transforming growth factor β (TGF-β) and contains activated fibroblastic aggregates that progressively increase in size and stiffness with activation of known fibrotic molecular and cellular changes. We used this model as a phenotypic drug discovery platform for modulators of fibrosis. We validated this platform by identifying a compound that promotes resolution of fibrosis in in vivo and ex vivo models of ocular and lung fibrosis

Актуальні питання реалізації іпотечних зобов'язань в нотаріальному процесі

Стаття присвячена теоретичному дослідженню важливості використання існуючих механізмів превентивної юстиції та дієвості правозахисної функції нотаріату. Доведено, що нотаріус як гарант превентивності правовідносин реалізує свої правозахисні функції не лише на стадії реалізації іпотечних зобовязань, шляхом вчинення виконавчого напису на борговому документі, а і на стадії узгодження та викладення всіх істотних умов договору. Ключові слова: нотаріат; правозахисна функція нотаріату; виконання зобовязань; превентивна юстиція.Статья посвящена теоретическому исследованию необходимости использования существующих механизмов превентивной юстиции и действенности правозащитной функции нотариата. Доказывается, что нотариус как гарант превентивности правоотношений реализует свои правозащитные функции не только на стадии реализации ипотечных обязательств, в связи с совершением исполнительной надписи на долговом документе, а и на стадии согласования и изложения всех существенных условий договора. Ключевые слова: нотариат; правозащитная функция нотариату; исполнение обязательств; превентивная юстиция.This article is dedicated into theoretical research of importance in using special mechanism of prevention justitia and acting law defender functions of notoriety. It is argued that notaries as a guaranty of prevention law relation realizes his law defender functions not only on the stage of realization ipothek obligations, making performance inscription on the duty document, but on the stage of consenting and stating all existence conditions of contract. Key words: notoriety, law defender function of notaries, making obligations, prevention justitia

A Search for Technosignatures Around 11,680 Stars with the Green Bank Telescope at 1.15-1.73 GHz

We conducted a search for narrowband radio signals over four observing sessions in 2020-2023 with the L-band receiver (1.15-1.73 GHz) of the 100 m diameter Green Bank Telescope. We pointed the telescope in the directions of 62 TESS Objects of Interest, capturing radio emissions from a total of ~11,680 stars and planetary systems in the ~9 arcminute beam of the telescope. All detections were either automatically rejected or visually inspected and confirmed to be of anthropogenic nature. In this work, we also quantified the end-to-end efficiency of radio SETI pipelines with a signal injection and recovery analysis. The UCLA SETI pipeline recovers 94.0% of the injected signals over the usable frequency range of the receiver and 98.7% of the injections when regions of dense RFI are excluded. In another pipeline that uses incoherent sums of 51 consecutive spectra, the recovery rate is ~15 times smaller at ~6%. The pipeline efficiency affects calculations of transmitter prevalence and SETI search volume. Accordingly, we developed an improved Drake Figure of Merit and a formalism to place upper limits on transmitter prevalence that take the pipeline efficiency and transmitter duty cycle into account. Based on our observations, we can state at the 95% confidence level that fewer than 6.6% of stars within 100 pc host a transmitter that is detectable in our search (EIRP > 1e13 W). For stars within 20,000 ly, the fraction of stars with detectable transmitters (EIRP > 5e16 W) is at most 3e-4. Finally, we showed that the UCLA SETI pipeline natively detects the signals detected with AI techniques by Ma et al. (2023).Comment: 22 pages, 9 figures, submitted to AJ, revise

K0S and Λ production in Pb-Pb collisions at sNN−−−−√=2.76 TeV

The ALICE measurement of K0S and Λ production at midrapidity in Pb-Pb collisions at sNN−−−√=2.76  TeV is presented. The transverse momentum (pT) spectra are shown for several collision centrality intervals and in the pT range from 0.4  GeV/c (0.6  GeV/c for Λ) to 12  GeV/c. The pT dependence of the Λ/K0S ratios exhibits maxima in the vicinity of 3  GeV/c, and the positions of the maxima shift towards higher pT with increasing collision centrality. The magnitude of these maxima increases by almost a factor of three between most peripheral and most central Pb-Pb collisions. This baryon excess at intermediate pT is not observed in pp interactions at s√=0.9  TeV and at s√=7  TeV. Qualitatively, the baryon enhancement in heavy-ion collisions is expected from radial flow. However, the measured pT spectra above 2  GeV/c progressively decouple from hydrodynamical-model calculations. For higher values of pT, models that incorporate the influence of the medium on the fragmentation and hadronization processes describe qualitatively the pT dependence of the Λ/K0S ratio

Performance of the ALICE experiment at the CERN LHC

ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables

Centrality Dependence Of The Pseudorapidity Density Distribution For Charged Particles In Pb-pb Collisions At √snn=2.76tev

7264/Mai61062

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Measurement of charged jet suppression in Pb-Pb collisions at sNN \sqrt{{{s_{\mathrm{NN}}}}} = 2.76 TeV

A measurement of the transverse momentum spectra of jets in Pb-Pb collisions at √sNN = 2.76TeV is reported. Jets are reconstructed from charged particles using the anti-k T jet algorithm with jet resolution parameters R of 0.2 and 0.3 in pseudo-rapidity |η| < 0.5. The transverse momentum p T of charged particles is measured down to 0.15 GeV/c which gives access to the low p T fragments of the jet. Jets found in heavy-ion collisions are corrected event-by-event for average background density and on an inclusive basis (via unfolding) for residual background fluctuations and detector effects. A strong suppression of jet production in central events with respect to peripheral events is observed. The suppression is found to be similar to the suppression of charged hadrons, which suggests that substantial energy is radiated at angles larger than the jet resolution parameter R = 0.3 considered in the analysis. The fragmentation bias introduced by selecting jets with a high p T leading particle, which rejects jets with a soft fragmentation pattern, has a similar effect on the jet yield for central and peripheral events. The ratio of jet spectra with R = 0.2 and R = 0.3 is found to be similar in Pb-Pb and simulated PYTHIA pp events, indicating no strong broadening of the radial jet structure in the reconstructed jets with R < 0.3