Miracle-dz/UniFAR-FTUs huggingface dataset:
Crowder titrations enable the quantification of driving forces for macromolecular phase separation

Macromolecular solubility is an important contributor to the driving forces for phase separation. Formally, the driving forces in a binary mixture comprising a macromolecule dissolved in a solvent can be quantified in terms of the saturation concentration, which is the threshold macromolecular concentration above which the mixture separates into coexisting dense and dilute phases. Additionally, the second virial coefficient, which measures the effective strength of solvent-mediated intermolecular interactions provides direct assessments of solvent quality. The sign and magnitude of second virial coefficients will be governed by a combination of solution conditions and the nature of the macromolecule of interest. Here, we show, using a combination of theory, simulation, and in vitro experiments, that titrations of crowders, providing they are true depletants, can be used to extract the intrinsic driving forces for macromolecular phase separation. This refers to saturation concentrations in the absence of crowders and the second virial coefficients that quantify the magnitude of the incompatibility between macromolecules and the solvent. Our results show how the depletion-mediated attractions afforded by crowders can be leveraged to obtain comparative assessments of macromolecule-specific, intrinsic driving forces for phase separation. SIGNIFICANCE Phase separation has emerged as a process of significant relevance to sorting macromolecules into distinct compartments, thereby enabling spatial and temporal control over cellular matter. Considerable effort is being invested into uncovering the driving forces that enable the separation of macromolecular solutions into coexisting phases. At its heart, this process is governed by the balance of macromolecule-solvent, inter-macromolecule, and solvent-solvent interactions. We show that the driving forces for phase separation, including the coefficients that measure interaction strengths between macromolecules, can be extracted by titrating the concentrations of crowders that enable macromolecules to phase separate at lower concentrations. Our work paves the way to leverage specific categories of measurements for quantitative characterizations of driving forces for phase separation.
Microvascular plasticity in stroke recovery: Longitudinal snapshots, network statistical analysis, and dynamics

This research article quantitatively investigates neuro-microvascular network remodeling dynamics following stroke using a novel in vivo two-photon angiography (cubic millimeter volume, weekly snapshots) and high throughput (thousands of connected capillaries) vascular vectorization method. The results suggest distinct temporal patterns of cere-brovascular plasticity, with acute remodeling peaking at one week post-stroke. The network architecture then gradually stabilizes, returning to a new steady state after four weeks. These findings align with previous literature on neuronal plasticity, highlighting the correlation between neuronal and neurovascular remodeling. Quantitative analysis of neurovascular networks using length- and strand-based statistical measures reveals intri-cate changes in network anatomy and topology. The distance and strand-length statistics show significant alterations, with a peak of plasticity observed at one week post-stroke, followed by a gradual return to baseline. The orientation statistic plasticity peaks at two weeks, gradually approaching the (conserved across subjects) stroke signature. The underlying mechanism of the vascular response (angiogenesis vs. tissue deformation), however, is yet unelucidated, requiring network registration advancements. Overall, the combination of two-photon angiography, vectorization, reconstruction/visualization, and statistical analysis enables both qualitative and quantitative assessments of neu-rovascular remodeling dynamics, demonstrating an impactful method for investigating neuro-microvascular network disorders and the therapeutic modes of action thereof. Understanding the timing and nature of neurovascular remodeling allows for optimized interventions, including personalized medicine for stroke rehabilitation. Additionally, the evaluation of pharmaceutical interventions using these tools may facilitate targeted drug development. Furthermore, neurovascular coupling dynamics have implications for neurodegenerative diseases, brain aging, and the field of brain-computer interfaces.
Seasonal forecast skill for extratropical cyclones and windstorms

Extratropical cyclones and their associated extreme wind speeds are a major cause of vast damage and large insured losses in several European countries. Reliable seasonal predictions of severe extratropical winter cyclones and associated windstorms would thus have great social and economic benefits, especially in the insurance sector. We analyse the climatological representation and assess the seasonal prediction skill of wintertime extratropical cyclones and windstorms in three multi‐member seasonal prediction systems: ECMWF‐System3, ECMWF‐System4 and Met Office‐GloSea5, based on hindcasts over a 20‐year period (1992–2011).
WANG TILE SIZE IN TERMS OF CIRCULAR PARTICLE DYNAMICS

The main advantage of the Wang tiling concept for material engineering is ability to create large material domains with a relatively small set of tiles. Such idea allows both a reduction of computational demands and preserving heterogeneity of a reconstructed media in comparison with traditional cell concepts. This work is dealing with a random heterogeneous material composed of monodisperse circular hard particles within a matrix. The Wang tile sets are generated via algorithm with molecular dynamics and adaptive boundaries approach. Even though previous works proved usefulness of the Wang tiling for material reconstruction, still plenty of questions remain unanswered. In here we would like to provide simulations with emphasis on the overall particle distribution and the ratio of hard disc number to tile size. The results and discussion should followers help with settings of both tile generations and the tiling algorithms when creating samples of various degree of heterogeneity.
Uncovering Novel Roles of miR-122 in the Pathophysiology of the Liver: Potential Interaction with NRF1 and E2F4 Signaling

MicroRNA miR-122 plays a pivotal role in liver function. Despite numerous studies investigating this miRNA, the global network of genes regulated by miR-122 and its contribution to the underlying pathophysiological mechanisms remain largely unknown. To gain a deeper understanding of miR-122 activity, we employed two complementary approaches. Firstly, through transcriptome analysis of polyribosome-bound RNAs, we discovered that miR-122 exhibits potential antagonistic effects on specific transcription factors known to be dysregulated in liver disease, including nuclear respiratory factor-1 (NRF1) and the E2F Transcription Factor 4 (E2F4). Secondly, through proteome analysis of hepatoma cell transfected with either miR-122 mimic or antagomiR we discovered changes in several proteins associated with increased malignancy. Interestingly, many of these proteins were reported to be transcriptionally regulated by NRF1 and E2F4, six of which we validated as miR-122 targets. Among these, a negative correlation was observed between miR-122 and glucose-6-phosphate dehydrogenase levels in the livers of patients with hepatitis B virus-associated hepatocellular carcinoma. This study provides novel insights into potential alterations of molecular pathway occurring at the early stages of liver disease, driven by the dysregulation of miR-122 and its associated genes.
Inference for entomological semi-field experiments: Fitting a mathematical model assessing personal and community protection of vector-control interventions

The effectiveness of vector-control tools is often assessed by experiments as a reduction in mosquito landings using human landing catches (HLCs). However, HLCs alone only quantify a single characteristic and therefore do not provide information on the overall impacts of the intervention product. Using data from a recent semi-field study which used time-stratified HLCs, aspiration of non-landing mosquitoes, and blood feeding, we suggest a Bayesian inference approach for fitting such data to a stochastic model. This model considers both personal protection, through a reduction in biting, and community protection, from mosquito mortality and disarming (prolonged inhibition of blood feeding). Parameter estimates are then used to predict the reduction of vectorial capacity induced by etofenpox-treated clothing, picaridin topical repellents, transfluthrin spatial repellents and metofluthrin spatial repellents, as well as combined interventions for Plasmodium falciparum malaria in Anopleles minimus. Overall, all interventions had both personal and community effects, preventing biting and killing or disarming mosquitoes. This led to large estimated reductions in the vectorial capacity, with substantial impact even at low coverage. As the interventions aged, fewer mosquitoes were killed; however the impact of some interventions changed from killing to disarming mosquitoes. Overall, this inference method allows for additional modes of action, rather than just reduction in biting, to be parameterised and highlights the tools assessed as promising malaria interventions.
Spinal facilitation of descending motor input

Highly varying patterns of electrostimulation (Dynamic Stimulation, DS) delivered to the dorsal cord through an epidural array with 18 independent electrodes transiently facilitate corticospinal motor responses, even after spinal injury. To partly unravel how corticospinal input are affected by DS, we introduced a corticospinal platform that allows selective cortical stimulation during the multisite acquisition of cord dorsum potentials (CDPs) and the simultaneous supply of DS. Firstly, the epidural interface was validated by the acquisition of the classical multisite distribution of CDPs on the dorsal cord and their input-output profile elicited by pulses delivered to peripheral nerves. Apart from increased EMGs, DS selectively increased excitability of the spinal interneurons that first process corticospinal input, without changing the magnitude of commands descending from the motor cortex, suggesting a novel correlation between muscle recruitment and components of cortically-evoked CDPs. Finally, DS increases excitability of post-synaptic spinal interneurons at the stimulation site and their responsiveness to any residual supraspinal control, thus supporting the use of electrical neuromodulation whenever the motor output is jeopardized by a weak volitional input, due to a partial disconnection from supraspinal structures and/or neuronal brain dysfunctions.
A Diagnostic PDF Cloud Scheme to Improve Subtropical Low Clouds in NCAR Community Atmosphere Model (CAM5)

Low clouds strongly impact the radiation budget of the climate system, but their simulation in most GCMs has remained a challenge, especially over the subtropical stratocumulus region. Assuming a Gaussian distribution for the subgrid‐scale total water and liquid water potential temperature, a new statistical cloud scheme is proposed and tested in NCAR Community Atmospheric Model version 5 (CAM5). The subgrid‐scale variance is diagnosed from the turbulent and shallow convective processes in CAM5. The approach is able to maintain the consistency between cloud fraction and cloud condensate and thus alleviates the adjustment needed in the default relative humidity‐based cloud fraction scheme. Short‐term forecast simulations indicate that low cloud fraction and liquid water content, including their diurnal cycle, are improved due to a proper consideration of subgrid‐scale variance over the southeastern Pacific Ocean region. Compared with the default cloud scheme, the new approach produced the mean climate reasonably well with improved shortwave cloud forcing (SWCF) due to more reasonable low cloud fraction and liquid water path over regions with predominant low clouds. Meanwhile, the SWCF bias over the tropical land regions is also alleviated. Furthermore, the simulated marine boundary layer clouds with the new approach extend further offshore and agree better with observations. The new approach is able to obtain the top of atmosphere (TOA) radiation balance with a slightly alleviated double ITCZ problem in preliminary coupled simulations. This study implies that a close coupling of cloud processes with other subgrid‐scale physical processes is a promising approach to improve cloud simulations.
Time-Efficacy in SMA Type 1 and 2 Cases Treated with Nusinersen

Spinal muscular atrophy is a neuromuscular degenerative disorder characterized by progressive apoptosis of motor neurons, with severe weakness and bulbar dysfunction. The aim of the study was to analyze the correlations between the moment of initiation of treatment (nusinersen) and clinical evolution, and also the change of electrophysiological parameters and motor scales, fol-lowed up for 2 years. This study was carried out between 2018 and 2022 on 60 SMA children (29 girls, 31 boys), (29 type 1 and 31 type 2; 29 with 2 copies of SMN2, 29 with 3 copies, and 2 with 4 copies), aged between 3 weeks and 196 months, divided into 2 groups according type of SMA. For both types of SMA, statistically significant negative correlations were found between the elapsed interval from the onset of the disease to the initiation of treatment and upper motor acquisitions (type 1: p < 0.0001, r = -0.713, type 2: p<0.001, r = -0.560) and between age at the beginning of treatment and improvement in motor function (type 1: p <0.0001, r =-0.726, type 2: p<0.001, r=-0.553). For patients with type 2 SMA, a negative correlation was also identified between age at the time of onset and motor evolution (p<0.05, r = -0.378). Electrophysiological parameters were strongly positive correlated with motor improvement (p<0.0001, r=0.600). Our study established the necessity of early SMA diagnosis and therapy beginning, and demonstrated that Compound Motor Action Potential can be a predictive factor in the disease's progression. Keywords: Compound Motor Action Potential; motor scales; Spinal Muscular Atrophy
Lipoxin receptor agonist and inhibition of LTA4 hydrolase prevent tight junction disruption caused by P. aeruginosa filtrate in airway epithelial cells

Airway diseases can disrupt tight junction proteins, compromising the epithelial barrier and making it more permeable to pathogens. In people with pulmonary disease who are prone to infection with Pseudomonas aeruginosa, pro-inflammatory leukotrienes are increased and anti-inflammatory lipoxins are decreased. Upregulation of lipoxins is effective in counteracting inflammation and infection. However, whether combining a lipoxin receptor agonist with a specific leukotriene A4 hydrolase (LTA4H) inhibitor could enhance these protective effects has not to our knowledge been investigated. Therefore, we explored the effect of lipoxin receptor agonist BML-111 and JNJ26993135 a specific LTA4H inhibitor that prevents the production of pro-inflammatory LTB4 on tight junction proteins disrupted by P. aeruginosa filtrate (PAF) in human airway epithelial cell lines H441 and 16HBE-14o. Pre-treatment with BML-111 prevented an increase in epithelial permeability induced by PAF and conserved ZO-1 and claudin-1 at the cell junctions. JNJ26993135 similarly prevented the increased permeability induced by PAF, restored ZO-1 and E-cadherin and reduced IL-8 but not IL-6. Cells pre-treated with BML-111 plus JNJ26993135 restored TEER and permeability, ZO-1 and claudin-1 to the cell junctions. Taken together, these data indicate that the combination of a lipoxin receptor agonist with a LTA4H inhibitor could provide a more potent therapy.
Possible Ameliorative and Preventive Effect of Leaf Extract of Andrographis paniculata on Atherosclerosis: An Experience with Isoproterenol Induced Wistar Rats

Atherosclerosis has been regarded as one of the leading causes of death in modern-day man worldwide. The use of medicinal plants especially Andrographis paniculata in the treatment of chronic diseases, particularly atherosclerotic disorder is becoming popular. This study aimed to evaluate the possible ameliorative and preventive effect of leaf extract of Andrographis paniculata on atherosclerosis in isoproterenol-induced Wistar rats. Thirty animals were randomly divided into five groups (A-E) of six animals per group, per cage. Groups A, B and C served as the treatment groups and were orally pre-treated with 100, 200 and 400 mg/kg body weight extract of A. paniculata for fourteen days, group D served as the positive control group and was administered 10 mg atorvastatin while group E served as the negative control and was administered distilled water. On the fifteenth and sixteenth day, 150 mg/kg isoproterenol was administered intraperitoneal at 24 h intervals to all the animals and were subsequently sacrificed. The sera obtained were used for a bioassay study. Analysis of serum total cholesterol, triglycerides, low density lipoprotein (LDL) and high density lipoprotein (HDL) were carried out using standard methods. The result obtained revealed a significant decrease (p>0.05) in the serum total cholesterol, triglycerides and LDL in the extract treated groups in a dose dependent manner when compared with the untreated control while there was a significant increase in the serum HDL level of extract treated group compared to the untreated control; thereby supporting the protective effect of A. paniculata against atherosclerotic disorder.
PCDH7 as the key gene related to the co-occurrence of sarcopenia and osteoporosis

Sarcopenia and osteoporosis, two degenerative diseases in older patients, have become severe health problems in aging societies. Muscles and bones, the most important components of the motor system, are derived from mesodermal and ectodermal mesenchymal stem cells. The adjacent anatomical relationship between them provides the basic conditions for mechanical and chemical signals, which may contribute to the co-occurrence of sarcopenia and osteoporosis. Identifying the potential common crosstalk genes between them may provide new insights for preventing and treating their development. In this study, DEG analysis, WGCNA, and machine learning algorithms were used to identify the key crosstalk genes of sarcopenia and osteoporosis; this was then validated using independent datasets and clinical samples. Finally, four crosstalk genes (ARHGEF10, PCDH7, CST6, and ROBO3) were identified, and mRNA expression and protein levels of PCDH7 in clinical samples from patients with sarcopenia, with osteoporosis, and with both sarcopenia and osteoporosis were found to be significantly higher than those from patients without sarcopenia or osteoporosis. PCDH7 seems to be a key gene related to the development of both sarcopenia and osteoporosis.
The human gut phageome: composition, development, and alterations in disease

The human gastrointestinal tract is colonized by a large number of microorganisms, including bacteria, archaea, viruses, and eukaryotes. The bacterial community has been widely confirmed to have a significant impact on human health, while viruses, particularly phages, have received less attention. Phages are viruses that specifically infect bacteria. They are abundant in the biosphere and exist in a symbiotic relationship with their host bacteria. Although the application of high-throughput sequencing and bioinformatics technology has greatly improved our understanding of the genomic diversity, taxonomic composition, and spatio-temporal dynamics of the human gut phageome, there is still a large portion of sequencing data that is uncharacterized. Preliminary studies have predicted that the phages play a crucial role in driving microbial ecology and evolution. Prior to exploring the function of phages, it is necessary to address the obstacles that hinder establishing a comprehensive sequencing database with sufficient biological properties and understanding the impact of phage–bacteria interactions on human health. In this study, we provide an overview of the human gut phageome, including its composition, structure, and development. We also explore the various factors that may influence the phageome based on current research, including age, diet, ethnicity, and geographical location. Additionally, we summarize the relationship between the phageome and human diseases, such as IBD, IBS, obesity, diabetes, and metabolic syndrome.
Quantitative Easing Spillovers

This paper studies the spillover effects of US quantitative easing on emerging market economies. I estimate the spillover effects using Bayesian VAR models for the US economy and a set of emerging market economies. A 1% increase in the Federal Reserves securities held outright has positive and statistically significant effects on real GDP, real Investment, the price level, and asset prices in the US economy. Emerging market economies experience positive statistically significant effects on real GDP, real investment, inflation, and stock market indices, along with currency appreciation, current account deterioration, and increase in their long-term bond yields. Then I build a two-country Heterogeneous-Agents New Keynesian model with QE shocks and dollarized bank balance sheets in the EME. The model is estimated to match the empirical movements. Bank balance sheets are at the heart of the international transmission mechanism. The choice between HANK vs. RANK matters for the magnitude of the impulse responses since the absence of heterogeneity leads to lower aggregate demand in both countries. The model predicts that QE decreases inequality in the medium run, but in the short run, wealth inequality rises in the US economy, whereas in the emerging market economy wealth inequality increases and remains elevated over time. Finally, policies aiming to reduce the flow of capital between countries, such as capital controls, have significant adverse effects on economic activity and welfare. *I am thankful to my advisors, Eduardo Davila, William B. English, and John Geanakoplos, for their invaluable guidance and support. I also thank Giuseppe Moscarini, Fabrizio Zilibotti, and the rest of the participants at the Yale Macro Seminar for their helpful comments. Any remaining errors are my own. †Department of Economics, Yale University. Email: antzelos.kyriazis@yale.edu