Hybridizing Constraint Programming and Monte-Carlo Tree Search: Application to the Job Shop problem

International audienceConstraint Programming (CP) solvers classically explore the solution space using tree search-based heuristics. Monte-Carlo Tree-Search (MCTS), a tree-search based method aimed at sequential decision making under uncertainty, simultaneously estimates the reward associated to the sub-trees, and gradually biases the exploration toward the most promising regions. This paper examines the tight combination of MCTS and CP on the job shop problem (JSP). The contribution is twofold. Firstly, a reward function compliant with the CP setting is proposed. Secondly, a biased MCTS node-selection rule based on this reward is proposed, that is suitable in a multiple-restarts context. Its integration within the Gecode constraint solver is shown to compete with JSP-specific CP approaches on difficult JSP instances

Longevity of Crown Margin Repairs Using Glass Ionomer Cement: A Retrospective Study

Objective: The objective of this study was to determine the survival time of crown margin repairs (CMRs) with glass ionomer and resin-modified glass ionomer cements on permanent teeth using electronic dental record (EDR) data. Methods: We queried a database of EDR (axiUm; Exan Group, Coquitlam, BC, Canada) in the Indiana University School of Dentistry (IUSD), Indianapolis, IN, USA, for records of patients who underwent CMRs of permanent teeth at the Graduate Operative Dentistry Clinic. Two examiners developed guidelines for reviewing the records and manually reviewed the clinical notes of patient records to confirm for CMRs. Only records that were confirmed with the presence of CMRs were retained in the final dataset for survival analysis. Survival time was calculated by Kaplan-Meier statistics, and a Cox proportional hazards model was performed to assess the influence of age, gender, and tooth type on survival time (a<0.05). Results: A total of 214 teeth (115 patients) with CMR were evaluated. Patient average age was 69.4 ± 11.7 years old. Posterior teeth accounted for 78.5% (n=168) of teeth treated. CMRs using glass ionomer cements had a 5-year survival rate of 62.9% and an annual failure rate (AFR) of 8.9%. Cox proportional-hazards model revealed that none of the factors examined (age, gender, tooth type) affected time to failure. Conclusion: The results indicate the potential of CMRs for extending the functional life of crowns with defective margins, thus reducing provider and patient burden of replacing an indirect restoration. We recommend future studies with a larger population who received CMR to extend the generalizability of our findings and to determine the influence of factors such as caries risk and severity of defects on survival time

Building a recruitment database for asthma trials: a conceptual framework for the creation of the UK Database of Asthma Research Volunteers

Funded by Asthma UK as part of the Asthma UK Centre for Applied Research (AUK-AC-2012-01). In addition, BN, IS, CS and AS acknowledge the support of the Farr Institute, which is funded by the MRC and its consortium of funders

Ouabain Stimulates a Na+/K+-ATPase-Mediated SFK-Activated Signalling Pathway That Regulates Tight Junction Function in the Mouse Blastocyst

The Na+/K+-ATPase plays a pivotal role during preimplantation development; it establishes a trans-epithelial ionic gradient that facilitates the formation of the fluid-filled blastocyst cavity, crucial for implantation and successful pregnancy. The Na+/K+-ATPase is also implicated in regulating tight junctions and cardiotonic steroid (CTS)-induced signal transduction via SRC. We investigated the expression of SRC family kinase (SFK) members, Src and Yes, during preimplantation development and determined whether SFK activity is required for blastocyst formation. Embryos were collected following super-ovulation of CD1 or MF1 female mice. RT-PCR was used to detect SFK mRNAs encoding Src and Yes throughout preimplantation development. SRC and YES protein were localized throughout preimplantation development. Treatment of mouse morulae with the SFK inhibitors PP2 and SU6656 for 18 hours resulted in a reversible blockade of progression to the blastocyst stage. Blastocysts treated with 10−3 M ouabain for 2 or 10 minutes and immediately immunostained for phosphorylation at SRC tyr418 displayed reduced phosphorylation while in contrast blastocysts treated with 10−4 M displayed increased tyr418 fluorescence. SFK inhibition increased and SFK activation reduced trophectoderm tight junction permeability in blastocysts. The results demonstrate that SFKs are expressed during preimplantation development and that SFK activity is required for blastocyst formation and is an important mediator of trophectoderm tight junction permeability

SNAI1 and SNAI2 Are Asymmetrically Expressed at the 2-Cell Stage and Become Segregated to the TE in the Mouse Blastocyst

SNAI1 and SNAI2 are transcription factors that initiate Epithelial-to-Mesenchymal cell transitions throughout development and in cancer metastasis. Here we show novel expression of SNAI1 and SNAI2 throughout mouse preimplantation development revealing asymmetrical localization of both SNAI1 and SNAI2 in individual blastomeres beginning at the 2-cell stage through to the 8-cell stage where SNAI1 and SNAI2 are then only detected in outer cells and not inner cells of the blastocyst. This study implicates SNAI1 and SNAI2 in the lineage segregation of the trophectoderm and inner cell mass, and provides new insight into these oncogenes

Enhancing Physical Geography schools outreach: insights from co-production and storytelling narratives

Global environmental change is one of the most pressing issues facing future generations. Equipping schoolchildren with a clear understanding of physical geography is therefore a key educational priority. Effectively engaging schoolchildren with complex scientific ideas can be challenging, but with the appropriate tools, scientists can play a valuable role in developing meaningful science communication experiences. Climate Explorers addressed these issues by forging a collaboration between physical geography and social science academics, and 320 UK school students and their teachers in seven primary (elementary) schools. Using insights from co-production techniques and storytelling, the project aimed to 1) produce new open access, online climate science education resources, and 2) test co-production and storytelling approaches to physical geography science engagement. Our findings demonstrated that school children responded especially well to working with ‘real life’ scientists, where meaningful and memorable educational interactions were forged through the use of narratives, personal experiences and tailored language. Here we summarise our approach, and provide templates that can be readily applied by scientists working across the physical geography spectrum anywhere in the world. The flexibility of the templates means that they can be adapted and developed for a range of formats, from small-scale community workshops to national-scale educational initiatives, for delivery both in-person or online. We hope that our approach will provide a springboard to transform and enhance physical geography science communication more broadly

Genome Sizes and the Benford Distribution

BACKGROUND: Data on the number of Open Reading Frames (ORFs) coded by genomes from the 3 domains of Life show the presence of some notable general features. These include essential differences between the Prokaryotes and Eukaryotes, with the number of ORFs growing linearly with total genome size for the former, but only logarithmically for the latter. RESULTS: Simply by assuming that the (protein) coding and non-coding fractions of the genome must have different dynamics and that the non-coding fraction must be particularly versatile and therefore be controlled by a variety of (unspecified) probability distribution functions (pdf's), we are able to predict that the number of ORFs for Eukaryotes follows a Benford distribution and must therefore have a specific logarithmic form. Using the data for the 1000+ genomes available to us in early 2010, we find that the Benford distribution provides excellent fits to the data over several orders of magnitude. CONCLUSIONS: In its linear regime the Benford distribution produces excellent fits to the Prokaryote data, while the full non-linear form of the distribution similarly provides an excellent fit to the Eukaryote data. Furthermore, in their region of overlap the salient features are statistically congruent. This allows us to interpret the difference between Prokaryotes and Eukaryotes as the manifestation of the increased demand in the biological functions required for the larger Eukaryotes, to estimate some minimal genome sizes, and to predict a maximal Prokaryote genome size on the order of 8-12 megabasepairs. These results naturally allow a mathematical interpretation in terms of maximal entropy and, therefore, most efficient information transmission

Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.

ContextPreeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.ObjectiveTo investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44.Design and interventionFKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling.Settings and participantsHuman samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid.Main outcome measuresPreeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signaling in trophoblast and endothelial cells were assessed.ResultsThe CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, P = 0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signaling, enhancing cell angiogenesis.ConclusionsThe FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes

Temperature and population density influence SARS-CoV-2 transmission in the absence of nonpharmaceutical interventions

As COVID-19 continues to spread across the world, it is increasingly important to understand the factors that influence its transmission. Seasonal variation driven by responses to changing environment has been shown to affect the transmission intensity of several coronaviruses. However, the impact of the environment on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains largely unknown, and thus seasonal variation remains a source of uncertainty in forecasts of SARS-CoV-2 transmission. Here we address this issue by assessing the association of temperature, humidity, ultraviolet radiation, and population density with estimates of transmission rate (R). Using data from the United States, we explore correlates of transmission across US states using comparative regression and integrative epidemiological modeling. We find that policy intervention (“lockdown”) and reductions in individuals’ mobility are the major predictors of SARS-CoV-2 transmission rates, but, in their absence, lower temperatures and higher population densities are correlated with increased SARS-CoV-2 transmission. Our results show that summer weather cannot be considered a substitute for mitigation policies, but that lower autumn and winter temperatures may lead to an increase in transmission intensity in the absence of policy interventions or behavioral changes. We outline how this information may improve the forecasting of COVID-19, reveal its future seasonal dynamics, and inform intervention policies

External fixation compared to intramedullary nailing of tibial fractures in the rat

Background and purpose It is not known whether there is a difference in bone healing after external fixation and after intramedullary nailing. We therefore compared fracture healing in rats after these two procedures