Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of high durability concrete for the Arabian Gulf environment

Concrete is probably the most widely used construction material in the world. In the Arabian Gulf region, deterioration of concrete due to the aggressive environment is recognized to be the main factor affecting their structural integrity. The durability of concrete structures can be preserved by various protection methods; however, using cement replacement materials is one of the most effective and economic methods of maintaining their stability as well as extending their service life. The aim of this project is to study four interrelated aspects, namely, (1) the effect of hot environment on the properties of fresh concrete incorporating mineral admixtures, (2), the influence of exposure environment on the engineering properties of hardened concrete, under various curing conditions, without and with mineral admixture, (3), the differences in porosity and pore structure of the same set of mixes, and, (4) the effect of outdoor exposure on the durability-related properties of concrete. To achieve the above aims, the experimental programme involved the study of five different mixes of combinations of silica fume/slag and silica fume. The effects of real exposure to the Arabian Gulf environment of these mixes subjected to four curing regimes, namely, continuous water curing, no water curing after demolding, and air drying after 3 and 7 days of initial water curing were investigated. The properties investigated include (1) consistency and setting times of cement pastes, workability and workability loss with time, (2) engineering properties such as compressive strength, dynamic modulus of elasticity, pulse velocity, shrinkage, expansion and thermal expansion, (3) microstructural properties such as porosity and pore size distribution, (4) durability-related properties such as permeability, water absorption and carbonation depth. The results show that exposure to hot environment results in rapid setting times, faster loss of slump, higher porosity, coarser pore structure and more permeable concretes. It was found that part cement replacement by silica fume and slag improves the quality of concrete mixtures, refined the pore structure and produced concretes with very low porosity and continuous pore diameter in both indoor and outdoor environment. The properties of concrete containing mineral admixture appear to be more sensitive to poor curing than the plain concrete, with the sensitivity increasing with increasing amount of slag in the mixture.
Quality control mechanisms exclude incorrect polymerases from the eukaryotic replication fork

Significance DNA replication is a central life process and is performed by numerous proteins that orchestrate their actions to separate the strands of duplex DNA and produce two new copies of the genome for cell division. While the antiparallel architecture of DNA is elegant in its simplicity, replication of DNA still holds many mysteries. For example, many essential replication proteins still have unknown functions. In eukaryotes the two DNA strands are duplicated by different DNA polymerases. The mechanism by which these different polymerases target to their respective strands is understood. This report examines the mechanisms that eject incorrect polymerases when they associate with the wrong strand. The eukaryotic genome is primarily replicated by two DNA polymerases, Pol ε and Pol δ, that function on the leading and lagging strands, respectively. Previous studies have established recruitment mechanisms whereby Cdc45-Mcm2-7-GINS (CMG) helicase binds Pol ε and tethers it to the leading strand, and PCNA (proliferating cell nuclear antigen) binds tightly to Pol δ and recruits it to the lagging strand. The current report identifies quality control mechanisms that exclude the improper polymerase from a particular strand. We find that the replication factor C (RFC) clamp loader specifically inhibits Pol ε on the lagging strand, and CMG protects Pol ε against RFC inhibition on the leading strand. Previous studies show that Pol δ is slow and distributive with CMG on the leading strand. However, Saccharomyces cerevisiae Pol δ–PCNA is a rapid and processive enzyme, suggesting that CMG may bind and alter Pol δ activity or position it on the lagging strand. Measurements of polymerase binding to CMG demonstrate Pol ε binds CMG with a Kd value of 12 nM, but Pol δ binding CMG is undetectable. Pol δ, like bacterial replicases, undergoes collision release upon completing replication, and we propose Pol δ–PCNA collides with the slower CMG, and in the absence of a stabilizing Pol δ–CMG interaction, the collision release process is triggered, ejecting Pol δ on the leading strand. Hence, by eviction of incorrect polymerases at the fork, the clamp machinery directs quality control on the lagging strand and CMG enforces quality control on the leading strand.
Identification and Characterization of a Large Protein Essential for Degradation of the Crystalline Region of Cellulose by Cytophaga hutchinsonii

ABSTRACT Cytophaga hutchinsonii is a Gram-negative bacterium that can efficiently degrade crystalline cellulose by a unique mechanism different from the free cellulase or cellulosome strategy. In this study, chu_3220, encoding the hypothetical protein CHU_3220 (205 kDa), was identified by insertional mutation and gene deletion as the first gene essential for degradation of the crystalline region but not the amorphous region of cellulose by C. hutchinsonii. A chu_3220 deletion mutant was defective in the degradation of crystalline cellulose and increased the degree of crystallinity of Avicel PH101 but could still degrade amorphous cellulose completely. CHU_3220 was found to be located on the outer surface of the outer membrane and could bind to cellulose. It contains 15 PbH1 domains and a C-terminal domain (CHU_C) that was proved to be critical for the localization of CHU_3220 on the cell surface and the function of CHU_3220 in crystalline cellulose degradation. Moreover, the degradation of crystalline cellulose was intact-cell dependent and inhibited by NaN3. Further study showed that chu_3220 was induced by cellulose and that the endoglucanase activity on the cell surface was significantly reduced without chu_3220. Real-time PCR revealed that the transcription of most genes encoding endoglucanases located on the cell surface was decreased in the chu_3220 deletion mutant, indicating that chu_3220 might also play a role in the regulation of the expression of some endoglucanases. IMPORTANCE Cytophaga hutchinsonii could efficiently degrade crystalline cellulose with a unique mechanism without cellulosomes and free cellulases. It lacks proteins that are thought to play important roles in disruption of the crystalline region of cellulose, including exoglucanases, lytic polysaccharide monooxygenases, expansins, expansin-like proteins, or swollenins, and most of its endoglucanases lack carbohydrate binding modules. The mechanism of the degradation of crystalline cellulose is still unknown. In this study, chu_3220 was identified as the first gene essential for the degradation of the crystalline region but not the amorphous region of cellulose. CHU_3220 is a high-molecular-weight protein located on the outer surface of the outer membrane and could bind to cellulose. We proposed that CHU_3220 might be an essential component of a protein complex on the cell surface in charge of the decrystallization of crystalline cellulose. The degradation of crystalline cellulose by C. hutchinsonii was not only dependent on intact cells but also required the energy supplied by the cells. This was obviously different from other known cellulose depolymerization system. Our study has shed more light on the novel strategy of crystalline cellulose degradation by C. hutchinsonii.
Clear Aligners Generations and Orthodontic Tooth Movement

Clear aligner technology has evolved over the last 15 years, with these appliances continually being modified to increase the range of tooth movements that they can achieve. However, there is very little clinical research available to show how these appliances achieve their results. This article describes the different generations of clear aligners that are available and highlights their use. However, until more clinical research becomes available, aligners cannot be routinely prescribed as an effective alternative to fixed labial appliances.
Predictors of post-traumatic pituitary failure during long-term follow-up

OBJECTIVEThere is increasing awareness among physicians of the risks of traumatic brain injury (TBI)-induced hypopituitarism. We have assessed the prevalence and risk factors of posttraumatic hypopituitarism by analyzing the TBI database of the University of Pecs.DESIGNThis consecutive analysis of 126 TBI survivors (mean age: 42.4 years, average follow-up time: 48 months) revealed that 60.3% had severe and 39.7% moderately severe trauma based on GCS score. Subdural hemorrhage (29.3%) and diffuse injury (27%) were the most common types of injury; 17.5% of patients suffered basal skull fractures.RESULTSThe prevalence of major anterior pituitary failure was 57.1%. Occurrence of total and partial growth hormone deficiency (GHD/GHI) was 39.7%, while LH/FSH, TSH and ACTH deficiencies were less frequent, namely 23.0%, 16.7% and 10.3%, respectively. Of the 82 patients with multiple endocrine evaluations, 31.7% presented significant changes in hormonal deficiencies during the follow-up period: new hormone deficiencies developed in 16 patients, while hormonal disturbances resolved in 10 subjects. Looking for factors influencing the prevalence of pituitary dysfunction, endocrine results were analyzed in relation to age, gender, GCS scores, injury types, basal skull fracture, ventricular drain insertion and necessity of neurosurgical intervention. All hormonal disturbances were more prevalent after severe trauma (OR: 3.25, p = 0.002), while the need for surgery proved to be an independent determinant of multiple and GH deficits (OR: 3.72 (p = 0.004) and 9.33 (p = 0.001)). CONCLUSIONPost-traumatic hypopituitarism is common and may evolve or resolve over time. Victims of severe TBI and/or patients who have undergone neurosurgical intervention for head injury are the most prone to post-traumatic hypopituitarism.
Manners of Death in Drug‐Related Fatalities in Florida

To understand the mortality patterns among drug users and potential risk factors, we evaluated drug‐related deaths reported to the Florida Medical Examiners Commission from 2001 to 2013, by substances, demographics, and manner of death. The annual drug‐related fatalities increased by 57% from 2001 to 2013 (total n = 100,882); 51.8% were accidental, 7.9% homicide, 18.6% natural, and 19.6% suicide. The different manners of death exhibited distinct demographic profiles and drug composition. The gender gap was more prominent in homicide. Age ≥55 years was more closely associated with natural death and suicide. Age <35 years and central nervous system (CNS) stimulants including amphetamines and cocaine showed higher relative risks for accidental death and homicide, whereas CNS depressants including benzodiazepines, carisoprodol, opioids, and zolpidem were more strongly associated with accidental death and/or suicide. The findings aid in identifying populations more vulnerable to drug‐related deaths, developing targeted interventions and thereby improving efficiency of preventive efforts.
Dual Structured Convolutional Neural Network with Feature Augmentation for Quantitative Characterization of Tissue Histology

We present a dual convolutional neural network (dCNN) architecture for extracting multi-scale features from histological tissue images for the purpose of automated characterization of tissue in digital pathology. The dual structure consists of two identical convolutional neural networks applied to input images with different scales, that are merged together and stacked with two fully connected layers. It has been acknowledged that deep networks can be used to extract higher-order features, and therefore, the network output at final fully connected layer was used as a deep dCNN feature vector. Further, engineered features, shown in previous studies to capture important characteristics of tissue structure and morphology, were integrated to the feature extractor module. The acquired quantitative feature representation can be further utilized to train a discriminative model for classifying tissue types. Machine learning based methods for detection of regions of interest, or tissue type classification will advance the transition to decision support systems and computer aided diagnosis in digital pathology. Here we apply the proposed feature-augmented dCNN method with supervised learning in detecting cancerous tissue from whole slide images. The extracted quantitative representation of tissue histology was used to train a logistic regression model with elastic net regularization. The model was able to accurately discriminate cancerous tissue from normal tissue, resulting in blockwise AUC=0.97, where the total number of analyzed tissue blocks was approximately 8.3 million that constitute the test set of 75 whole slide images.
Understanding health-care access and utilization disparities among Latino children in the United States

It is important to understand the source of health-care disparities between Latinos and other children in the United States. We examine parent-reported health-care access and utilization among Latino, White, and Black children (≤17 years old) in the United States in the 2006–2011 National Health Interview Survey. Using Blinder-Oaxaca decomposition, we portion health-care disparities into two parts (1) those attributable to differences in the levels of sociodemographic characteristics (e.g., income) and (2) those attributable to differences in group-specific regression coefficients that measure the health-care ‘return’ Latino, White, and Black children receive on these characteristics. In the United States, Latino children are less likely than Whites to have a usual source of care, receive at least one preventive care visit, and visit a doctor, and are more likely to have delayed care. The return on sociodemographic characteristics explains 20–30% of the disparity between Latino and White children in the usual source of care, delayed care, and doctor visits and 40–50% of the disparity between Latinos and Blacks in emergency department use and preventive care. Much of the health-care disadvantage experienced by Latino children would persist if Latinos had the sociodemographic characteristics as Whites and Blacks.
Oral Anticoagulant Therapy Prescription in Patients With Atrial Fibrillation Across the Spectrum of Stroke Risk: Insights From the NCDR PINNACLE Registry.

IMPORTANCE Patients with atrial fibrillation (AF) are at a proportionally higher risk of stroke based on accumulation of well-defined risk factors. OBJECTIVE To examine the extent to which prescription of an oral anticoagulant (OAC) in US cardiology practices increases as the number of stroke risk factors increases. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional registry study of outpatients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry's PINNACLE (Practice Innovation and Clinical Excellence) Registry between January 1, 2008, and December 30, 2012. As a measure of stroke risk, we calculated the CHADS2 score and the CHA2DS2-VASc score for all patients. Using multinomial logistic regression models adjusted for patient, physician, and practice characteristics, we examined the association between increased stroke risk score and prescription of an OAC. MAIN OUTCOMES AND MEASURES The primary outcome was prescription of an OAC with warfarin sodium or a non-vitamin K antagonist OAC. RESULTS The study cohort comprised 429 417 outpatients with AF. Their mean (SD) age was 71.3 (12.9) years, and 55.8% were male. Prescribed treatment consisted of an OAC (192 600 [44.9%]), aspirin only (111 134 [25.9%]), aspirin plus a thienopyridine (23 454 [5.5%]), or no antithrombotic therapy (102 229 [23.8%]). Each 1-point increase in risk score was associated with increased odds of OAC prescription compared with aspirin-only prescription using the CHADS2 score (adjusted odds ratio, 1.158; 95% CI, 1.144-1.172; P < .001) and the CHA2DS2-VASc score (adjusted odds ratio, 1.163; 95% CI, 1.157-1.169; P < .001). Overall, OAC prescription prevalence did not exceed 50% even in higher-risk patients with a CHADS2 score exceeding 3 or a CHA2DS2-VASc score exceeding 4. CONCLUSIONS AND RELEVANCE In a large quality improvement registry of outpatients with AF, prescription of OAC therapy increased with a higher CHADS2 score and CHA2DS2-VASc score. However, a plateau of OAC prescription was observed, with less than half of high-risk patients receiving an OAC prescription.
Stabilization of Notch1 by the Hsp90 Chaperone is Crucial for T-Cell Leukemogenesis

Purpose: Notch1 deregulation is assuming a focal role in T-cell acute lymphoblastic leukemia (T-ALL). Despite tremendous advances in our understanding of Notch1 transcriptional programs, the mechanisms by which Notch1 stability and turnover are regulated remain obscure. The goal of the current study is to identify intracellular Notch1 (ICN1, the activated form of Notch1) binding partner(s) regulating its stability and activity. Experimental Design: We employed immunoaffinity purification to identify ICN1-associating partner(s) and used coimmunoprecipitation to verify the endogenous protein interaction. Pharmacologic or short hairpin RNA–mediated inhibition was applied in loss-of-function assays to assess the role of tentative binding partner(s) in modulating ICN1 protein stability as well as affecting T-ALL cell expansion in vitro and in vivo. Mechanistic analysis involved protein degradation and polyubiquitination assays. Results: We identify the Hsp90 chaperone as a direct ICN1-binding partner essential for its stabilization and transcriptional activity. T-ALL cells exhibit constitutive endogenous ICN1–Hsp90 interaction and Hsp90 depletion markedly decreases ICN1 levels. The Hsp90-associated E3 ubiquitin ligase Stub1 mediates the ensuring proteasome-dependent ICN1 degradation. Administration of 17-AAG or PU-H71, two distinct Hsp90 inhibitors, depletes ICN1, inhibits T-ALL cell proliferation, and triggers dramatic apoptotic cell death. Systemic treatment with PU-H71 reduces ICN1 expression and profoundly inhibits murine T-ALL allografts as well as human T-ALL xenografts. Conclusions: Our findings demonstrate Hsp90 blockade leads to ICN1 destabilization, providing an alternative strategy to antagonize oncogenic Notch1 signaling with Hsp90-selective inhibitors. Clin Cancer Res; 23(14); 3834–46. ©2017 AACR.
Circulating anti‐Müllerian hormone and breast cancer risk: A study in ten prospective cohorts

A strong positive association has been observed between circulating anti‐Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case–control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme‐linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (ptrend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31–1.94). Though the test for interaction was not statistically significant (pinteraction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: ORQ4–Q1 = 1.96, 95% CI = 1.46–2.64, ptrend <0.0001; ER+/PR−: ORQ4–Q1 = 0.82, 95% CI = 0.40–1.68, ptrend = 0.51; ER−/PR+: ORQ4–Q1 = 3.23, 95% CI = 0.48–21.9, ptrend = 0.26; ER−/PR−: ORQ4–Q1 = 1.15, 95% CI = 0.63–2.09, ptrend = 0.60. The association was observed for both pre‐ (ORQ4–Q1= 1.35, 95% CI = 1.05–1.73) and post‐menopausal (ORQ4–Q1 = 1.61, 95% CI = 1.03–2.53) breast cancer (pinteraction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.
Inferring epidemiologic dynamics from viral evolution: 2014–2015 Eurasian/North American highly pathogenic avian influenza viruses exceed transmission threshold, R 0 = 1, in wild birds and poultry in North America

Highly pathogenic avian influenza virus (HPAIV) is a multihost pathogen with lineages that pose health risks for domestic birds, wild birds, and humans. One mechanism of intercontinental HPAIV spread is through wild bird reservoirs, and wild birds were the likely sources of a Eurasian (EA) lineage HPAIV into North America in 2014. The introduction resulted in several reassortment events with North American (NA) lineage low‐pathogenic avian influenza viruses and the reassortant EA/NA H5N2 went on to cause one of the largest HPAIV poultry outbreaks in North America. We evaluated three hypotheses about novel HPAIV introduced into wild and domestic bird hosts: (i) transmission of novel HPAIVs in wild birds was restricted by mechanisms associated with highly pathogenic phenotypes; (ii) the HPAIV poultry outbreak was not self‐sustaining and required viral input from wild birds; and (iii) reassortment of the EA H5N8 generated reassortant EA/NA AIVs with a fitness advantage over fully Eurasian lineages in North American wild birds. We used a time‐rooted phylodynamic model that explicitly incorporated viral population dynamics with evolutionary dynamics to estimate the basic reproductive number (R0) and viral migration among host types in domestic and wild birds, as well as between the EA H5N8 and EA/NA H5N2 in wild birds. We did not find evidence to support hypothesis (i) or (ii) as our estimates of the transmission parameters suggested that the HPAIV outbreak met or exceeded the threshold for persistence in wild birds (R0 > 1) and poultry (R0 ≈ 1) with minimal estimated transmission among host types. There was also no evidence to support hypothesis (iii) because R0 values were similar among EA H5N8 and EA/NA H5N2 in wild birds. Our results suggest that this novel HPAIV and reassortments did not encounter any transmission barriers sufficient to prevent persistence when introduced to wild or domestic birds.
Virtual Blood Vessels in Complex Background Using Stereo X-Ray Images

We propose a fully automatic system to reconstruct and visualize 3D blood vessels in Augmented Reality (AR) system from stereo X-ray images with bones and body fat. Currently, typical 3D imaging technologies are expensive and carrying the risk of irradiation exposure. To reduce the potential harm, we only need to take two X-ray images before visualizing the vessels. Our system can effectively reconstruct and visualize vessels in following steps. We first conduct initial segmentation using Markov Random Field and then refine segmentation in an entropy based post-process. We parse the segmented vessels by extracting their centerlines and generating trees. We propose a coarse-to-fine scheme for stereo matching, including initial matching using affine transform and dense matching using Hungarian algorithm guided by Gaussian regression. Finally, we render and visualize the reconstructed model in a HoloLens based AR system, which can essentially change the way of visualizing medical data. We have evaluated its performance by using synthetic and real stereo X-ray images, and achieved satisfactory quantitative and qualitative results.