Miracle-dz/UniFAR-FTUs huggingface dataset:
A transient burst of mutations occurs during the normal development of yeast colonies

Characterizing the pace of mutation accumulation is crucial for understanding how populations adapt to their environment and for unraveling the intricate dynamics between gradual processes and more sudden burst-like events occurring during cancer development. We engineered the genome of Saccharomyces cerevisiae to measure the rates of single and double mutations, including point mutations, segmental duplications and reciprocal translocations. We found that during the development of wild-type yeast colonies, double mutations occur at rates that are up to 17-fold higher than those expected on the basis of single mutation rates. We found that this excess of double mutations is partially dependent on the ELG1/ATAD5 clamp unloader. Additionally, the double mutants retain wild-type mutation rates, suggesting that they originated from genetically wild-type cells that transiently expressed a mutator phenotype. Numerical simulations based on the experimentally measured mutation rates, confirmed that the excess of double mutations can be accounted for by subpopulations of transient mutators within the colony. These subpopulations would be limited to less than a few thousand cells and temporarily adopt mutation rates multiplied by hundreds or thousands for less than five generations. We found that the majority of double mutations would accumulate sequentially in different cell cycles. The simultaneous acquisition of both mutations during the same cell cycle would be rare and possibly associated with systemic genomic instability. In conclusion, our results suggest that transient hypermutators play a major role in genomic instability and contribute significantly to the mutational load naturally accumulating during the growth of isogenic cell populations. Significance statement Understanding the pace at which mutations accumulate is of paramount importance in the field of genome dynamics and evolution. In our study, we unveiled a surprising burst of mutations within growing yeast colonies, occurring independently of external stressors. This discovery indicates that, during short intervals, a small subset of cells within the colonies undergoes a mutational overdrive. Notably, these mutator cells do not represent genetically stable mutators with mutations in genes associated with genome stability. Instead, they stem from a strong mutator phenotype that was transiently expressed in genetically wild-type cells. This phenomenon, previously underestimated or even overlooked, holds significant importance and may have far-reaching implications, particularly in the context of cancer development.
Reinforcement Planning for Effective ε-Optimal Policies in Dense Time with Discontinuities

Lately, the model of (Decision) Stochastic Timed Automata (DSTA) has been proposed, to model those Cyber Physical Systems displaying dense time (physical part), discrete actions and discontinuities such as timeouts (cyber part). The state of the art results on controlling DSTAs are however not ideal: in the case of infinite horizon, optimal controllers do not exist, while for timed bounded behaviors, we do not know how to build such controllers, even ε -optimal ones. In this paper, we develop a theory of Reinforcement Planning in the setting of DSTAs, for discounted infinite horizon objectives. We show that optimal controllers do exist in general. Further, for DSTAs with 1 clock (which already generalize Continuous Time MDPs with e.g. timeouts), we provide an effective procedure to compute ε -optimal controllers. It is worth noting that we do not rely on the discretization of the time space, but consider symbolic representations instead. Evaluation on a DSTA shows that this method can be more efficient. Last, we show on a counterexample that this is the furthest this construction can go, as it cannot be extended to 2 or more clocks.
Growth Modeling With Latent Variables Using Mplus: Introductory And Intermediate Growth Models

136 Alternative Models With Time-Varying Covariates 169 Growth Modeling With Parallel Processes 182 Categorical Outcomes: Logistic and Probit Regression Growth Model With Individually Varying Times Of Observation 126 And Random Slopes For Time-Varying Covariates 159 Regressions Among Random Effects 107 Growth Model With Free Time Scores 125 Intermediate Growth Models 27 Growth Modeling Frameworks 4 General Latent Variable Modeling Framework
Interval Selection in Data Streams: Weighted Intervals and the Insertion-Deletion Setting

We study the Interval Selection problem in data streams: Given a stream of n intervals on the line, the objective is to compute a largest possible subset of non-overlapping intervals using O ( | OPT | ) space, where | OPT | is the size of an optimal solution. Previous work gave a 3 / 2-approximation for unit-length and a 2-approximation for arbitrary-length intervals [Emek et al., ICALP’12]. We extend this line of work to weighted intervals as well as to insertion-deletion streams. Our results include: 1. When considering weighted intervals, a (3 / 2+ ϵ )-approximation can be achieved for unit intervals, but any constant factor approximation for arbitrary-length intervals requires space Ω( n ). 2. In the insertion-deletion setting where intervals can both be added and deleted, we prove that, even without weights, computing a constant factor approximation for arbitrary-length intervals requires space Ω( n ), whereas in the weighted unit-length intervals case a (2 + ϵ )-approximation can be obtained. Our lower bound results are obtained via reductions to the recently introduced Chained-Index communication problem, further demonstrating the strength of this problem in the context of streaming geometric independent set problems
A Cointegration Rank Test of Market Linkages with an Application to the U.S. Natural Gas Industry

This research applies recently developed cointegration techniques to the measurement of market linkages when the data are nonstationary. Likelihood based tests for cointegration are applied to data from natural gas spot markets. The results indicate that natural gas spot markets at dispersed locations in the pipeline network are strongly connected. Most of the market pairs examined in the gas pipeline network satisfy a more stringent condition for perfect market integration.
Association of endothelial nitric oxide synthase gene variants in pre-eclampsia: an updated systematic review and meta-analysis

Abstract Introduction Three common endothelial nitric oxide synthase (eNOS) gene variants are existed such as; G-894T, T-786C, and variable number tandem repeats in intron-4 (VNTR intron-4) which has been proposed to be linked with PE. However, there is still debate regarding the findings. To address this, a review was conducted to assess the potential association of eNOS gene variants at these positions with the risk of PE. Methods PubMed, Scopus, Science Direct, Hinari, and African Journal Online databases and Google Scholar search engines were utilized to search studies published in English-language until 30 January 2023. The Joanna Briggs Institute Meta-Analysis instrument was used for data extraction process and the Newcastle-Ottawa Scale was used to appraise the quality of the included studies. Meta-regression analysis was conducted using Stata 14 statistical software. The pooled odds ratios (ORs) of fixed and random effect models were utilized to evaluate the association of eNOS gene polymorphism with the risk of PE at 95% CI. Publication bias was assessed using Egger’s test and a funnel plot. Results The study included 47 observational studies involving 13,795 pregnant women (6216 cases and 7579 controls). Pregnant women carrying TT and CC genotypes of eNOS gene at 894 and 786 positions were found to have a greater probability of developing PE as compared to GG and TT genotypes (OR = 1.54 vs. 1.43 and CI: 1.12 − 2.14 vs.1.02 – 2.00 at 95% CI), respectively. However, a significant association was not observed between aa genotype of eNOS gene in VNTR intron-4 region and risk of PE as compared to bb genotype (OR =1.26, 95% CI: 0.83 – 1.89). The allelic model of eNOS gene at all positions showed nonsignificant association with the risk of PE. Conclusions The women having eNOS gene variants at 894 and 786 positions showed a significant association with the risk of PE. Yet, the women having eNOS gene variant at intron-4 region showed nonsignificant association with the risk of PE. Thus, this study suggests that eNOS gene variants may play a role in the development of PE, but large-scale studies are required to inaugurate concrete evidence on the roles of eNOS gene variants in PE pathogenesis.
Amyloid-colocalizes with apolipoprotein B in absorptive cells of the small intestine

Background: Amyloid- is recognized as the major constituent of senile plaque found in subjects with Alzheimer's disease. However, there is increasing evidence that in a physiological context amyloid- may serve as regulating apolipoprotein, primarily of the triglyceride enriched lipoproteins. To consider this hypothesis further, this study utilized an in vivo immunological approach to explore in lipogenic tissue whether amyloid- colocalizes with nascent triglyceriderich lipoproteins. Results: In murine absorptive epithelial cells of the small intestine, amyloid- had remarkable colocalization with chylomicrons (Manders overlap coefficient = 0.73 ± 0.03 (SEM)), the latter identified as immunoreactive apolipoprotein B. A diet enriched in saturated fats doubled the abundance of both amyloid- and apo B and increased the overlap coefficient of the two proteins (0.87 ± 0.02). However, there was no evidence that abundance of the two proteins was interdependent within the enterocytes (Pearson's Coefficient < 0.02 ± 0.03), or in plasma (Pearson's Coefficient < 0.01). Conclusion: The findings of this study are consistent with the possibility that amyloid- is secreted by enterocytes as an apolipoprotein component of chylomicrons. However, secretion of amyloid appears to be independent of chylomicron biogenesis. Background Amyloid- is recognized as the principal protein in senile plaques in subjects with Alzheimer's disease (AD) [1]. Generated from the slicing of amyloid precursor protein (APP) by secretases, the synthesis of amyloid- can be differentially modulated by cellular lipid homeostasis. Studies in cell culture and in vivo suggest that cholesterol inhibits amyloid- biogenesis [2-4], although this effect may be dependent on the distribution of free and esterified cholesterol within the plasma membrane and within lipid rafts [5]. In contrast, in vivo studies found that chronic ingestion of diets enriched in saturated-fats (SFA) had a potent stimulatory effect on enterocytic amyloid- abundance [6]. Published: 22 October 2009 Lipids in Health and Disease 2009, 8:46 doi:10.1186/1476-511X-8-46 Received: 10 September 2009 Accepted: 22 October 2009 This article is available from: http://www.lipidworld. com/content/8/1/46 © 2009 Galloway et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Toroidal compactiﬁcation: the generalised ball case

We give an introduction to toroidal compactiﬁcation in two ways: ﬁrst we give an overview of the origins and uses of the construction, and then we work out many of the details in the concrete case of quotients of the generalised ball B ( a, b ) = U( a, b ) / ( U ( a ) × U ( b )).
Free‐surface Simulations of Newtonian and Non‐Newtonian Fluids with the Lattice Boltzmann Method

This paper describes the application of a three‐dimensional lattice Boltzmann method (LBM) to Newtonian and non‐Newtonian (Bingham fluid in this work) flows with free surfaces. A mass tracking algorithm was incorporated to capture the free surface, whereas Papanastasiou's modified model was used for Bingham fluids. The lattice Boltzmann method was first validated using two benchmarks: Newtonian flow through a square cross‐section tube and Bingham flow through a circular cross‐section tube. Afterward, the dam‐break problem for the Newtonian fluid and the slump test for Bingham fluid were simulated to validate the free‐surface‐capturing algorithm. The numerical results were in good agreement with analytical results, as well as other simulations, thereby proving the validity and correctness of the current method. The proposed method is a promising substitute for time‐consuming and costly physical experiments to solve problems encountered in geotechnical and geological engineering, such as the surge and debris flow induced by a landslide or earthquake.
Generative Human Action Tracking Based on Compressive Sensing

Action tracking and recognition is a challenge due to human deformation and complex scene system. Tracking-by-detection methods are used to solve appearance changes problem caused by viewpoint, occlusion, scale or deformation. Here we propose a robust object tracking and generative action recognition method. Compressive sensing is improved to track object with superpixels, and the generative structural part model is designed to be adaptive to variation of deformable object. We evaluate the method on challenging sequences. Also, we make qualitative and quantitative discussion. The results indicate the method is robust, and it is adaptive to deformable object tracking and action recognition.
Influence of Age, Heart Failure and ACE Inhibitor Treatment on Plasma Renin Activity in Children: Insights from a Systematic Review and the European LENA Project.

BACKGROUND Plasma renin activity (PRA) has gained relevance as prognostic marker in adults with heart failure. The use of PRA as a clinically meaningful parameter in children and children with heart failure requires a thorough knowledge of the factors that influence PRA to correctly assess PRA levels. We aim to evaluate the influence of age, heart failure and angiotensin-converting enzyme inhibitor (ACEi) on PRA levels in children. METHODS We conducted a systematic literature search to identify studies on PRA levels in healthy children and in children with heart failure. In addition, we analysed PRA data measured before (n = 35, aged 25 days-2.1 years), 4 hours after (n = 34) and within the first 8 days of enalapril treatment (n = 29) in children with heart failure from the European project Labeling of Enalapril from Neonates up to Adolescents (LENA). RESULTS Age has a profound effect on PRA levels in healthy children, as PRA levels in the literature are up to about 7 times higher in neonates than in older children. Children with heart failure younger than 6 months showed 3-4 times higher PRA levels than healthy peers in both the literature and the LENA studies. In the LENA studies, the ACEi enalapril significantly increased median predose PRA by a factor of 4.5 in children with heart failure after 4.7 ± 1.6 days of treatment (n = 29, p < 0.01). Prior to treatment with enalapril, LENA subjects with symptomatic heart failure (Ross score ≥3) had a significantly higher PRA than LENA subjects with asymptomatic heart failure of comparable age (Ross score ≤2, p < 0.05). CONCLUSIONS Age, heart failure and ACEi treatment have a notable influence on PRA and must be considered when assessing PRA as a clinically meaningful parameter. CLINICAL TRIAL REGISTRATION The trials are registered on the EU Clinical Trials Register (https://www.clinicaltrialsregister.eu). TRIAL REGISTRATION NUMBERS EudraCT 2015-002335-17, EudraCT 2015-002396-18.
Quarantined-TreeKEM: a Continuous Group Key Agreement for MLS, Secure in Presence of Inactive Users

—The recently standardized secure group messaging protocol “Messaging Layer Security” (MLS) is designed to ensure asynchronous communications within large groups, with an almost-optimal communication cost and the same security level as point-to-point secure messaging protocols such as “Signal”. In particular, the core sub-protocol of MLS, a Continuous Group Key Agreement (CGKA) called TreeKEM, must generate a common group key that respects the fundamental security properties of “post-compromise security” and “forward secrecy” which mitigate the effects of user corruption over time.
Ship collision avoidance based on deep deterministic policy gradients and beetle antenna search algorithm

—Continuous-action reinforcement learning methods (e.g., the deep deterministic policy gradient method (DDPG)) have attracted much attention in the ship collision avoidance area. To obtain potential flexible collision avoidance policies, the noise injection is widely used in the exploration of DDPG. In order to realize an adaptive exploration in DDPG for ship collision avoidance, an adaptive beetle antenna search-optimized DDPG (ABAS-DDPG) method is proposed in this study. The main idea of this method is to adapt the noise scale in the learning process simultaneously based on a beetle antenna search (BAS) algorithm, which utilizes the feedback from the critic in DDPG. The simulation results indicate that the proposed ABAS-DDPG method successfully adjusts the noise process automatically and obtains stabler and higher sum rewards than original DDPG in ship collision avoidance learning.
Aedes aegypti: inseticidas, mecanismos de ação e resistência

In Brazil, dengue is transmitted by Aedes aegypti. Aedes albopictus, a potential dengue vector, is spreading all over the country. The use of chemical insecticides is yet the main vector control component. The action of the main classes of compounds traditionally employed in Public Health is described, as well as the resistance mechanisms selected by vector populations. Alternative products, with potential to be used in the control of A. aegypti, including the biolarvicide Bti and some insect growth regulators, are also discussed. The authors aim at contributing with the rational insecticide use, taking into account the different components of the integrated control
Turbulent Drag Reduction at High Reynolds Number

We present direct measurements of substantial drag reduction at friction Reynolds numbers ( Re τ ) up to 12,800 using spanwise surface oscillations. These measurements were achieved in the high Reynolds number turbulent boundary layer wind tunnel at the University of Melbourne using a custom actuation system that generated an upstream traveling wave of spanwise wall-oscillations via moving slats. The drag reduction was measured via a combination of drag balance and hot-wire anemometry, and was paired with matched large-eddy simulations to identify the Reynolds number trends for ﬁxed sets of actuation parameters. The drag reduction was found to occur via two distinct physical pathways. The ﬁrst pathway, recognised by previous studies, involved actuating the surface at high frequencies, comparable to those of the small-scale eddies that dominate turbulence near the surface. This approach generated drag reduction levels up to 25% at Re τ = 6,000, consistent with previous predictions based on much lower Reynolds numbers, albeit with an estimated net power cost of 20-25%. The second pathway, however, was new and leveraged actuation at low frequencies comparable to those of the large-scale eddies farther from the surface. The measured drag reduction greatly exceeded all prior predictions for these parameters, producing drag reduction of 13% at Re τ = 12,800 with an estimated net power savings of up to 8%. Drag reduction obtained through this pathway, importantly, increased with Reynolds number, thereby opening up an unexpected, new avenue for reducing fuel consumption by transport vehicles.
Digital Commons@Georgia Southern Digital Commons@Georgia Southern

: As COVID-19 vaccination guidelines were issued by Advisory Committee on Immunization Practices (ACIP) and the Centers for Diseases Control and Prevention (CDC) across the US, each state and clinical provider instituted vaccine implementation and education policies and protocols for high-risk populations. However, current research has shown that while people with autoimmune diseases were listed by ACIP and CDC as a COVID-19 high-risk population, the rate of adherence to implementation and education protocols, as well as the prioritization of this sub-population as a high-risk group, varied among the clinicians and vaccinators thus impacting the hesitancy towards the COVID-19 vaccine and a correlation to low vaccination rates. The purpose of this review was to explore factors of COVID-19 vaccination hesitancy in people living with autoimmune diseases in relation to current implementation and education policies and protocols, as well as ethical and contextual factors, while providing possible implications. COVID-19 vaccine hesitancy in people living with autoimmune disease was greater than in the general population, as demonstrated by increased levels of overall mistrust and fear of potential risk and harmful side effects. Evidence has shown that COVID-19 vaccination is safe and effective for patients with autoimmune diseases. Additionally, the beneﬁts of COVID-19 vaccination outweigh its potential risks and adverse effects in this population. However, the non-adherence to policy and protocols, especially community education protocols, by those providing the vaccination have a negative impact on the overall perception of the vaccine and needs to be addressed at local and state levels in order to protect this population. Future research should provide strategies to guide collaborative efforts between government and local agencies in providing tailored vaccination campaigns to this population. In parallel with policy, COVID-19 vaccination intervention implementation and educational protocols should be developed with evidence-based guidelines for public health and clinical professionals that are targeted at this vulnerable high-risk population.
Effectiveness and Safety of Tenofovir Alafenamide in Treatment-Naïve and Treatment-Experienced Patients with Chronic Hepatitis B: Results of a Real-World Study from China

Background: Tenofovir alafenamide (TAF) has been effective against naïve patients with chronic hepatitis B (CHB) in phase 3 clinical trials. However, its real-world data are still limited. Objectives: This study aimed to investigate the effectiveness and safety of TAF in real-life situations in treatment-naïve (TN) and treatment-experienced (TE) CHB patients in China. Methods: This retrospective study enrolled TAF-treated patients between January 2019 and October 2020 at the outpatient clinic of West China Hospital. The primary endpoint was the rates of virologic response (VR), and the secondary endpoints were the proportion of normal alanine aminotransferase (ALT) and quantitative hepatitis B surface antigen (qHBsAg) levels. Safety endpoints comprised serum lipid profiles, changes in estimated glomerular filtration rate (eGFR), and serum creatinine (Scr). Results: A total of 161 TAF-treated patients were enrolled, including 49 TN patients and 112 TE patients. In the TN group, the VR rate at week 96 was 91.7% (22/24), and the proportion of normal ALT at week 96 was 95.8% (23/24). In the TE group, the VR rate at week 96 was 97.2% (69/71), and the proportion of normal ALT at week 96 was 90.1% (64/71). Serum qHBsAg levels decreased from 2930 to 1292 IU/mL in the TN group and 1158 to 533IU/mL in the TE group during 96 weeks of treatment (P = 0.05). For patients in the TN and TE groups, when compared to baseline measurements, serum creatinine increased (+7.91 vs. +6.62 mL/min/1.73 m2, P = 0.52) while eGFR decreased (-11.46 vs. -10.90 µmol/L, P = 0.82) at week 96. Simultaneously, triglycerides (TG) (+ 0.39 vs. + 0.31 mmol/L, P = 0.32), total cholesterol (TC) (+0.65 vs. +0.52 mmol/L, P = 0.02), and low-density lipoprotein cholesterol (LDL-C) (+0.25 vs. +0.25 mmol/L, P = 0.60) increased over time. Conclusions: TAF was highly effective in TN and TE CHB patients. However, there are potential risks in eGFR decrease and a continuous increase in lipidemia with the prolongation of medication time.