Miracle-dz/UniFAR-FTUs huggingface dataset:
The CovRS Environmental Sensor Directly Controls the ComRS Signaling System To Orchestrate Competence Bimodality in Salivarius Streptococci

Combining production of antibacterial compounds and uptake of DNA material released by dead cells, competence is one of the most efficient survival strategies in streptococci. Yet, this powerful tactic is energy consuming and reprograms the metabolism to such an extent that cell proliferation is transiently impaired. ABSTRACT In bacteria, phenotypic heterogeneity in an isogenic population compensates for the lack of genetic diversity and allows concomitant multiple survival strategies when choosing only one is too risky. This powerful tactic is exploited for competence development in streptococci where only a subset of the community triggers the pheromone signaling system ComR-ComS, resulting in a bimodal activation. However, the regulatory cascade and the underlying mechanisms of this puzzling behavior remained partially understood. Here, we show that CovRS, a well-described virulence regulatory system in pathogenic streptococci, directly controls the ComRS system to generate bimodality in the gut commensal Streptococcus salivarius and the closely related species Streptococcus thermophilus. Using single-cell analysis of fluorescent reporter strains together with regulatory mutants, we revealed that the intracellular concentration of ComR determines the proportion of competent cells in the population. We also showed that this bimodal activation requires a functional positive-feedback loop acting on ComS production, as well as its exportation and reinternalization via dedicated permeases. As the intracellular ComR concentration is critical in this process, we hypothesized that an environmental sensor could control its abundance. We systematically inactivated all two-component systems and identified CovRS as a direct repression system of comR expression. Notably, we showed that the system transduces its negative regulation through CovR binding to multiple sites in the comR promoter region. Since CovRS integrates environmental stimuli, we suggest that it is the missing piece of the puzzle that connects environmental conditions to (bimodal) competence activation in salivarius streptococci. IMPORTANCE Combining production of antibacterial compounds and uptake of DNA material released by dead cells, competence is one of the most efficient survival strategies in streptococci. Yet, this powerful tactic is energy consuming and reprograms the metabolism to such an extent that cell proliferation is transiently impaired. To circumvent this drawback, competence activation is restricted to a subpopulation, a process known as bimodality. In this work, we explored this phenomenon in salivarius streptococci and elucidated the molecular mechanisms governing cell fate. We also show that an environmental sensor controlling virulence in pathogenic streptococci is diverted to control competence in commensal streptococci. Together, those results showcase how bacteria can sense and transmit external stimuli to complex communication devices for fine-tuning collective behaviors.
The Role of Integration Host Factor in Escherichia coli Persister Formation

Persisters are phenotypic variants that survive exposure to antibiotics through temporary dormancy. Mutants with increased levels of persisters have been identified in clinical isolates, and evidence suggests these cells contribute to chronic infections and antibiotic treatment failure. ABSTRACT Persisters represent a small subpopulation of cells that are tolerant of killing by antibiotics and are implicated in the recalcitrance of chronic infections to antibiotic therapy. One general theme has emerged regarding persisters formed by different bacterial species, namely, a state of relative dormancy characterized by diminished activity of antibiotic targets. Within this framework, a number of studies have linked persister formation to stochastic decreases in energy-generating components, leading to low ATP and target activity. In this study, we screen knockouts in the main global regulators of Escherichia coli for their effect on persisters. A knockout in integration host factor (IHF) had elevated ATP and a diminished level of persisters. This was accompanied by an overexpression of isocitrate dehydrogenase (Icd) and a downregulation of isocitrate lyase (AceA), two genes located at the bifurcation between the tricarboxylic acid (TCA) cycle and the glyoxylate bypass. Using a translational ihfA-mVenus fusion, we sort out rare bright cells, and this subpopulation is enriched in persisters. Our results suggest that noise in the expression of ihf produces rare cells with low Icd/high AceA, diverting substrates into the glyoxylate bypass, which decreases ATP, leading to antibiotic-tolerant persisters. We further examine noise in a simple model, the lac operon, and show that a knockout of the lacI repressor increases expression of the operon and decreases persister formation. Our results suggest that noise quenching by overexpression serves as a general approach to determine the nature of persister genes in a variety of bacterial species and conditions. IMPORTANCE Persisters are phenotypic variants that survive exposure to antibiotics through temporary dormancy. Mutants with increased levels of persisters have been identified in clinical isolates, and evidence suggests these cells contribute to chronic infections and antibiotic treatment failure. Understanding the underlying mechanism of persister formation and tolerance is important for developing therapeutic approaches to treat chronic infections. In this study, we examine a global regulator, IHF, that plays a role in persister formation. We find that noise in expression of IHF contributes to persister formation, likely by regulating the switch between the TCA cycle that efficiently produces energy and the glyoxylate bypass. We extend this study to a simple model lac operon and show that when grown on lactose as the sole carbon source, noise in its expression influences ATP levels and determines persister formation. This noise is quenched by overexpression of the lac operon, providing a simple approach to test the involvement of a gene in persister formation.
Quantification of the Selective Advantage of Driver Mutations Is Dependent on the Underlying Model and Stage of Tumor Evolution

Measuring the selective fitness advantages provided by driver mutations has the potential to facilitate a precise quantitative understanding of cancer evolution. However, accurately measuring the selective advantage of driver mutations has remained a challenge in the field. Early studies reported small selective advantages of drivers, on the order of 1%, whereas newer studies report much larger selective advantages, as high as 1,200%. In this article, we argue that the calculated selective advantages of cancer drivers are dependent on the underlying mathematical model and stage of cancer evolution and that comparisons of numerical values of selective advantage without regard for the underlying model and stage can lead to spurious conclusions.
Residential Segregation and Emergency Department Utilization Among an Underserved Urban Emergency Department Sample in North Carolina

BACKGROUND Residential segregation is a spatial manifestation of structural racism. Racial disparities in emergency department (ED) utilization mirror social inequity in the larger community. We evaluated associations between residential segregation and ED utilization in a community with known disparities and geographically concentrated social and health risk. METHODS Cross-sectional data were collected from electronic medical records of 101 060 adult ED patients living in Mecklenburg County, North Carolina in 2017. Community context was measured as residential segregation using the dissimilarity index, categorized into quintiles (Q1–Q5) using 2013–2017 American Community Survey estimates, and residency in a public health priority area (PHPA). The outcome was measured as total ED visits during the study period. Associations between community context and ED utilization were modeled using Anderson’s behavioral model of health service utilization, and estimated using negative binomial regression, including interaction terms by race. RESULTS Compared to areas with the lowest proportions of Black residents (Q1), living in Q4 was associated with higher rates of ED utilization among Black/Other (AME = 0.11) and White (AME = 0.23) patients, while associations with living in Q5 were approximately equivalent (AME = 0.12). PHPA residency was associated with higher rates of ED utilization among Black/Other (AME = 0.10) and White patients (AME = 0.22). LIMITATIONS Associations should not be interpreted as causal, or be generalized to the larger community without ED utilization. Health system leakage is possible but limited. CONCLUSIONS Residential segregation is associated with higher rates of ED utilization, as are PHPA residency and other individual-level determinants.
The Influence of Environmental Value Orientations on the Overall Scuba Diving Experience within a Marine Protected Area

ABSTRACT Makumbirofa, S.D. and Saayman, A. , 2022. The influence of environmental value orientations on the overall scuba diving experience within a marine protected area. Journal of Coastal Research, 38(1), 168–181. Coconut Creek (Florida), ISSN 0749-0208. This paper reports on the findings of a discrete choice experiment that aims to value the different attributes of the scuba diving experience in the Portofino Marine Protected Area (MPA), taking into account the various environmental value orientations of the divers. The attributes were divided into five different qualities—water visibility, diver crowding, species diversity, species number, and the willingness to pay—whereas the general awareness of consequences scale measured value orientations. Using a self-administered choice questionnaire, divers were asked to state their choice from different sets of attributes. A sample of 556 completed questionnaires were collected, with each respondent answering two random choice cards representing a choice between two different sets of attributes. A multinomial logit model was used to estimate scuba divers' willingness to pay for the various environmental attributes. The findings show that the most valued attribute for scuba divers in the Portofino MPA is underwater visibility followed by a less crowded dive site. The divers are predominantly egoistic in their value orientation, indicating that pro-environmental behaviour and intentions stem from self-interest. Regulations and education programmes that emphasise direct benefits to divers' diving experience would therefore encourage pro-environmental behaviour.
Satellite Tracking Data Reveals High-Use Areas for Immature Bald Eagles from Kentucky

Abstract. Immature raptors often travel long distances and move nomadically from the time they leave their natal area to the time they are recruited into the breeding population. Emphasis on identifying the nesting and winter habitat of Bald Eagles (Haliaeetus leucocephalus) has overshadowed the need to understand the habitat and spatial use of young eagles prior to reaching maturity. We used satellite telemetry to track the movements of immature Bald Eagles hatched in western Kentucky during 2010–2016. We analyzed movement data to identify high-use areas for eagles in their first and second years during warm and cool periods. Five out of seven eagles migrated north to the Great Lakes region during their first year. Using Brownian Bridge Movement Modelling, we identified 47 noncontiguous high-use areas during the warm period and 67 during the cool period. Public lands comprised 17% of warm period high-use areas and 43% of cool period high-use areas. High-use areas were located in Illinois, Indiana, Kentucky, Arkansas and Tennessee, and were often near federally-owned dams, rivers with sandbars, or areas with abundant waterfowl. Our small sample of tracked eagles correctly identified known Bald Eagle concentration areas within the study area; thus, we infer that previously unrecognized high-use areas identified by this study are likely to be concentration areas important to the larger population. We further suggest remote sensing data, even in limited datasets, as an efficient way to identify Bald Eagle concentration areas.
The crystal structure of 2-(2-methyl-6-phenyl-4H-pyran-4-ylidene)-1H-indene-1,3(2H)-dione, C21H14O3

Abstract C21H14O3, monoclinic, P21/c (no. 14), a = 4.8318(8) Å, b = 26.590(4) Å, c = 11.821(2) Å, β = 91.050(4)°, V = 1518.4(4) Å3, Z = 4, R gt (F) = 0.0401, wR ref (F) = 0.1038, T = 296(2) K. CCDC no.: 2122345
The crystal structure of (E)-3-chloro-2-(2-(4-methylbenzylidene)hydrazinyl)pyridine, C13H12ClN3

Abstract C13H12ClN3, orthorhombic, Fdd2 (no. 43), a = 28.7760(11) Å, b = 41.7393(17) Å, c = 8.5929(3) Å, V = 10,320.8(7) Å3, Z = 32, R gt (F) = 0.0477, wR ref (F2) = 0.0976, T = 296 K.
Aryl hydrocarbon receptor is a prognostic biomarker and is correlated with immune responses in cervical cancer

ABSTRACT Aryl hydrocarbon receptor (AHR) plays an important role in tumor development. However, its function in cervical cancer has not been fully elucidated. We evaluated the ten genes that are predicted to associate with AHR protein interaction. The comprehensive scores were: CYP1A1, ARNT2, HSP90AA1, ARNT, AIP, PTGES3, HSP90AB1, CYP1B1, ESR1, MAF, respectively. In addition, we showed that levels of AHR and its related genes were correlated with the immune infiltration and expression of immuno-regulators (immunoinhibitors, immunostimulators, MHC molecules) levels in cervical cancer. High expression of AHR, CYP1A1, HSP90AA1, and HSP90AB1 and low expression of ESR1 were negatively correlated with the prognoses of cervical cancer patients. The Cox multivariate regression showed that high expression of AHR (HR = 1.874, 95% CI = 1.069–3.285, P= 0.028) and CYP1A1 (HR = 1.822, 95%CI = 1.077–3.080, P= 0.025) were risk factors for prognosis in patients with cervical cancer. IHC results indicated that AHR and CYP1A1 were widely expressed in cervical cancer. These findings suggest that AHR and CYP1A1 may serve as prognostic biomarkers for determining prognosis and immune infiltration in cervical cancer.
Understanding middle leaders’ concerns in curriculum change: a missing perspective

ABSTRACT This paper is a case study evaluating the concerns that middle leaders in Singapore schools had as they implemented a large-scale English language curriculum reform. Drawing on in-depth interviews, the study aimed to gain insights into middle leaders’ perspectives. Its findings indicated that middle leadership could exert a substantial influence on educational change within a school. Not only were they able to influence their teachers’ understanding, but they also held some sway over the teachers’ receptivity towards and enactment of the reform. In addition, there were commonalities among the middle leaders’ concerns about the curriculum reform. As reform policies tend to differ from school priorities, failure to address middle leaders’ concerns has wide implications for curriculum reform and implementation.
Formative assessment in English language teaching: exploring the enactment practices of teachers within three primary schools in Singapore

ABSTRACT This article explores formative assessment enactment practices of six lower primary teachers within three primary schools in Singapore. Using a case study approach, data from interviews and lesson observations were examined to determine teachers’ formative assessment enactment practices and the influences to their enactment attempts. Findings from the study suggest formative assessment implementation to be complex when the teachers conceptualized and then enacted their practice. The teachers were found to play out processes and practices related to formative assessment based on interpretations they held. The teachers’ institutional, social and cultural settings were also found to influence their enactment practices. The study discusses evidences drawn before outlining implications for formative assessment implementation in schools.
Biased Credibility and Sharing of Fake News on Social Media: Considering Peer Context and Self-Objectivity State

ABSTRACT Several studies have examined the consumption and spread of fake news on social media. Two notable gaps, though, exist in the extant literature. First, prior research has focused on the political orientation of users while ignoring the broader context of sharing, namely the perceived political orientation of their social media peers. Second, there is limited insight about how user states, especially those related to their judgment abilities, influence the critical evaluation of fake news on social media. This paper addresses these gaps by theorizing the roles of perceived peer political orientation and self-objectivity states of users in translating biased credibility assessments of fake news into biased sharing intentions. It reports on an 7experiment (n=408) that primed self-perceived objectivity (a state) in half of the participants to examine its efficacy in moderating the influence of credibility bias (the extent to which users believe the news that highlight ideas that are consistent with their political orientation more than fake news articles that highlight ideas that are inconsistent with their political orientation) on sharing bias (the extent to which they are likely to share fake news that highlight ideas that are consistent with their political orientation more than fake news that highlight ideas that are inconsistent with their political orientation) while accounting for the moderating effect of perceived peer political orientation (a contextual factor). We found that consistency of fake news with people’s political orientation increased credibility bias and sharing bias and that credibility bias increased sharing bias. We also found that perceived alignment between a user and their peers’ political orientation, as a social context, reduced the effect of credibility bias on sharing bias. Finally, we found mixed support for the moderating effects of primed self-objectivity on the influence of credibility bias on sharing bias; it affected only liberal-leaning participants.
The Effect of Platform Intervention Policies on Fake News Dissemination and Survival: An Empirical Examination

ABSTRACT Fake news on social media has become a serious problem, and social media platforms have started to actively implement various interventions to mitigate its impact. This paper focuses on the effectiveness of two platform interventions, namely a content-level intervention (i.e., a fake news flag that applies to a single post) and an account-level intervention (i.e., a forwarding restriction policy that applies to the entire account). Collecting data from China’s largest social media platform, we study the impact of a fake news flag on three fake news dissemination patterns using a propensity score matching method with a difference-in-differences approach. We find that implementing a policy of using fake news flag influences the dissemination of fake news in a more centralized manner via direct forwards and in a less dispersed manner via indirect forwards, and that fake news posts are forwarded more often by influential users. In addition, compared with truthful news, fake news is disseminated in a less centralized and more dispersed manner and survives for a shorter period after a forwarding restriction policy is implemented. This study provides causal empirical evidence of the effect of a fake news flag on fake news dissemination. We also expand the literature on platform interventions to combat fake news by investigating a less studied account-level intervention. We discuss the practical implications of our results for social media platform owners and policymakers.
Shooting Down the Server Front-End Bottleneck

The front-end bottleneck is a well-established problem in server workloads owing to their deep software stacks and large instruction footprints. Despite years of research into effective L1-I and BTB prefetching, state-of-the-art techniques force a trade-off between metadata storage cost and performance. Temporal Stream prefetchers deliver high performance but require a prohibitive amount of metadata to accommodate the temporal history. Meanwhile, BTB-directed prefetchers incur low cost by using the existing in-core branch prediction structures but fall short on performance due to BTB’s inability to capture the massive control flow working set of server applications. This work overcomes the fundamental limitation of BTB-directed prefetchers, which is capturing a large control flow working set within an affordable BTB storage budget. We re-envision the BTB organization to maximize its control flow coverage by observing that an application’s instruction footprint can be mapped as a combination of its unconditional branch working set and, for each unconditional branch, a spatial encoding of the cache blocks around the branch target. Effectively capturing a map of the application’s instruction footprint in the BTB enables highly effective BTB-directed prefetching that outperforms the state-of-the-art prefetchers by up to 10% for equivalent storage budget.
SIGACT News Online Algorithms Column 38

In this column, we will discuss some papers in online algorithms that appeared in 2021. As usual, we make no claim at complete coverage here, and have instead made a selection. If we have unaccountably missed your favorite paper and you would like to write about it or about any other topic in online algorithms, please don't hesitate to contact us!
COVID-19's Impact on China's Strategic Emerging Industries: An Observation of Policy Difficulties

The study investigates the influence of the COVID-19 on the rate of R&D investment and foreign exchange development of China's most important emerging industry firms. From 2010 to 2020, data were collected from 26 locations across China, focusing on seven different types of critical creating companies. To analyze the data, we have applied Fourier Increased Unit Root Test, Granger causality assessments test, Pattern Assessment test, Poisson pseudo most excellent probability (PPML) approach, Wald test, and Regression analysis test. The results of the tests reveal a clear underlying association among COVID-19 relates Chinese exports and imports. COVID-19's instant effects on imports and exports lack working capital have been calculated, but the short-term, medium-to-long-term products are composite and unidentified. The article result main results are following: (i) The COVID-19 impacts the R&D investment is main industries like as high-end equipment industry, new materials industry, and new-era data innovation. (ii) The COVID-19 highly affects the imports and exports development network of Chinese strategic emerging industries which emphasizes cross-industry grouping features. The study provides the guidance to the future researchers to focus on COVID-19 affects on the strategic emerging industries of developed and underdeveloped countries to determine of foreign direct investment inflow and unemployment growth rates. JEL: G20, O10, O40