Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimization Model for the Design of Multi-layered Permeable Reactive Barriers

Permeable reactive barriers (PRBs) are employed as in situ groundwater remediation technology. The installation of PRBs is usually a major investment, where one of the biggest cost drivers are material costs. PRBs are barriers against contaminants moving under the natural gradient, however not against groundwater contaminants. The most common construction of a PRB is a single barrier, but in the case of contaminant mixtures a multi-layered construction, i.e. a combination of different reactive materials and removal processes, is required. The most important parameters for PRB design are dimensions. The barrier must be long enough to treat the entire width of the plume (dimension perpendicular to groundwater flow) and should extend to and be keyed into an impermeable layer. The problem is to determine the optimal thickness of a PRB, which should provide a residence time appropriate for reducing the concentration of contaminants to the desired effluent concentration. In PRBs, design is accomplished using numerical methods or simulators, which are useful to predict the scenarios and evaluate the resulting groundwater flow systems to specific site conditions. On the other hand, numerical methods are complicated and may have significant errors if the discretization is too coarse or is incorrectly aligned. This paper deals with a simple, conceptual model of a one-approach optimization method for multi-layered PRB design. Based on literature and laboratory test results (residence time, density and hydraulic coefficient), a selection of layers of reactive materials was determined. Considering the lowest cost of the reactive materials, the required thicknesses of activated carbon, zeolite and zero valent iron were calculated using two different algorithms. The simple model may be used for preliminary barrier design and cost calculations. Using the optimization model in a preliminary design stage, it is possible to reject the PRB concept and avoid losing time for the complicated analysis.
Electron correlation in real time.

Electron correlation, caused by the interaction among electrons in a multielectron system, manifests itself in all states of matter. A complete theoretical description of interacting electrons is challenging; different approximations have been developed to describe the fundamental aspects of the correlation that drives the evolution of simple (few-electron systems in atoms/molecules) as well as complex (multielectron wave functions in atoms, molecules, and solids) systems. Electron correlation plays a key role in the relaxation mechanisms that characterize excited states of neutral or ionized atoms and molecules populated by absorption of extreme ultraviolet (XUV) or X-ray radiation. The dynamics of these states can lead to different processes such as Fano resonance and Auger decay in atoms or interatomic Coulombic decay or charge migration in molecules and clusters. Many of these relaxation mechanisms are ubiquitous in nature and characterize the interaction of complex systems, such as biomolecules, adsorbates on surfaces, and hydrogen-bonded clusters, with XUV light. These mechanisms evolve typically on the femtosecond (1 fs=10(-15) s) or sub-femtosecond timescale. The experimental availability of few-femtosecond and attosecond (1 as=10(-18) s) XUV pulses achieved in the last 10 years offers, for the first time, the opportunity to excite and probe in time these dynamics giving the possibility to trace and control multielectron processes. The generation of ultrashort XUV radiation has triggered the development and application of spectroscopy techniques that can achieve time resolution well into the attosecond domain, thereby offering information on the correlated electronic motion and on the correlation between electron and nuclear motion. A deeper understanding of how electron correlation works could have a large impact in several research fields, such as biochemistry and biology, and trigger important developments in the design and optimization of electronic devices.
Animating a Camera for Viewing a Planar Polygon

Many applications, ranging from visualization applications such as architectural walkthroughs to robotic applications such as surveillance, could benefit from an automatic camera trajectory planner. This paper deals with that problem. We have automated the process of inspecting the outside of a simple two-dimensional polygon, given a few user parameters. Our algorithm preprocesses the polygon using Visibility Graph like concepts, and creates a visibility data structure for each polygon edge. From these structures, "good" camera zones are computed. Natural cubic splines are then used to create a closed camera trajectory that passes solely inside the zones. An iterative process refines the trajectory by minimizing a cost function until it converges to the optimal result. CR
Poxvirus uracil‐DNA glycosylase—An unusual member of the family I uracil‐DNA glycosylases

Uracil‐DNA glycosylases are ubiquitous enzymes, which play a key role repairing damages in DNA and in maintaining genomic integrity by catalyzing the first step in the base excision repair pathway. Within the superfamily of uracil‐DNA glycosylases family I enzymes or UNGs are specific for recognizing and removing uracil from DNA. These enzymes feature conserved structural folds, active site residues and use common motifs for DNA binding, uracil recognition and catalysis. Within this family the enzymes of poxviruses are unique and most remarkable in terms of amino acid sequences, characteristic motifs and more importantly for their novel non‐enzymatic function in DNA replication. UNG of vaccinia virus, also known as D4, is the most extensively characterized UNG of the poxvirus family. D4 forms an unusual heterodimeric processivity factor by attaching to a poxvirus‐specific protein A20, which also binds to the DNA polymerase E9 and recruits other proteins necessary for replication. D4 is thus integrated in the DNA polymerase complex, and its DNA‐binding and DNA scanning abilities couple DNA processivity and DNA base excision repair at the replication fork. The adaptations necessary for taking on the new function are reflected in the amino acid sequence and the three‐dimensional structure of D4. An overview of the current state of the knowledge on the structure‐function relationship of D4 is provided here.
Promoting arrhythmia susceptibility.

The SCN5A -encoded voltage-gated cardiac sodium channel α-subunit (hNaV1.5) is one of the critical ion channels necessary to orchestrate both the cardiac action potential and excitation-contraction coupling of the ventricular myocyte.1 Rare mutations in SCN5A have been implicated in a cadre of the cardiac channelopathies, including congenital long-QT syndrome (LQTS), Brugada syndrome (BrS), progressive cardiac conduction disease, idiopathic ventricular fibrillation, autosomal recessive sick sinus syndrome, sudden infant death syndrome, and even a cardiomyopathic electropathy characterized by dilated cardiomyopathy, conduction disease, and atrial fibrillation.1–9 In addition, some common nonsynonymous single nucleotide polymorphisms (cSNPs or coding polymorphisms) may increase the risk of drug-induced torsade de pointes and sudden cardiac death, particularly among blacks, whereas other cSNPs may result in a “reduced depolarization capacity. ”10–12 Article p 338 Now, because of this international all-star cast of channelologists, the proverbial street lamp is shining on a new location in the SCN5A gene and has illuminated an excitingly novel genetic mechanism that may promote arrhythmia susceptibility. In this issue of Circulation , Bezzina and colleagues13 reveal their discovery of a novel ethnic-specific promoter variant (HapB) that may genetically reduce the “antifibrillatory reserve” of a host. To appreciate the magnitude of these investigators’ sleuthing, one must consider where the street lamp has been shining for the past decade. Since the sentinel discovery of SCN5A as a disease gene for LQTS in 1995,1 SCN5A genetic testing has focused on the 27 translated exons that encode the 2015 or 2016 amino acids of the channel (depending on which alternatively spliced SCN5A transcript is generated). To date, ≈56 LQT3-associated mutations (mostly missense) and 77 BrS1-associated mutations (mostly missense) have been reported.2,3,14,15 This compendium of rare LQT3/BrS1-associated SCN5A mutations can be viewed at the web-based Inherited Arrhythmias Database (http://pc4.fsm.it:81/cardmoc). In general, gain-of-function mutations confer susceptibility …
Stochastic Micro-Meso Modeling of Cross-Ply Composites for Prediction of Softening

Composites are extensively using in modern industry (aircraft and automobile manufacturing, construction, etc.). Nowadays high-strength and lightweight composite materials, such as FRPs, exhibit elastic and strength anisotropy and deform nonlinearly at high stresses. Also, such materials have small enough failure strain in comparison with metals, and they are drastically more expensive than steel and aluminum alloys. The most important task in the design of structures made of composite materials is the minimization of its weight without loss of strength properties. We presented the method for modeling a UD FRP with randomly arranged fibers at the micro-and meso-level. These two approaches were compared on the problem of the composite panel tension. The selection of the mesomodel mechanical characteristics was based on data of the micro-level model. In the mesomodel, the damage accumulation of middle layer (90° layer) was simulated using the Stochastic Failure criterion (random Mott scatter of layer strength). The calculated curves and data, obtained in micro-and mesomodels, correlate well with each other.
A Phase I Study of Concurrent Weekly Carboplatin and Paclitaxel Combined With Intensity-Modulated Pelvic Radiotherapy as an Adjuvant Treatment for Early-Stage Cervical Cancer Patients With Positive Pelvic Lymph Nodes

Objectives The objective of this study was to determine the maximum tolerated dose (MTD) and acute dose-limiting toxicities (DLTs) of intravenous carboplatin plus paclitaxel combined with intensity-modulated pelvic radiotherapy (pelvic IMRT) as an adjuvant treatment for early-stage cervical cancer patients with positive pelvic lymph nodes. Methods Women with uterine cervical cancer who were treated with radical hysterectomy and pelvic lymphadenectomy and displayed positive pelvic lymph nodes were eligible for this study. The patients were postoperatively treated with pelvic IMRT (50.4 Gy). The concurrent weekly chemotherapy consisted of carboplatin (area under the curve [AUC], 2) and paclitaxel (starting at 35 mg/m2 and escalating by 5 mg/m2 in 3 patient cohorts). The primary end point of the escalation study was acute DLT that occurred within 30 days of the completion of radiation therapy. Results Nine patients were enrolled and treated at 2 dose levels until DLT occurred. The median age of the patients was 47 years (range, 28–66 years). The median radiotherapy treatment time was 39.5 days (range, 38–64 days). At dose level I (35 mg/m2 paclitaxel), 2 grade 3 leukopenia and a neutropenia were observed, but no DLT occurred. At dose level II (40 mg/m2 paclitaxel), the first patient experienced a grade 2 hypersensitive reaction, which resulted in discontinuation of planned treatment. Thus, 2 more patients were evaluated at this dose level. Of these, 1 patient experienced febrile neutropenia, which was considered to be a DLT, and the other patient experienced long-lasting grade 3 leukopenia and grade 3 neutropenia, which resulted in the discontinuation of chemotherapy for 2 weeks (a DLT). We then evaluated 3 more patients at dose level 1, but no DLT occurred. The MTD of paclitaxel and carboplatin was thus defined as 35 mg/m2 and an AUC of 2.0, respectively. Conclusions Weekly paclitaxel/carboplatin and pelvic IMRT is a reasonable adjuvant treatment regimen for cervical cancer patients after radical hysterectomy. The MTD of paclitaxel and carboplatin for future phase II trials of this regimen is 35 mg/m2 and an AUC of 2.0, respectively.
The association between BMI and mortality using offspring BMI as an indicator of own BMI: large intergenerational mortality study

Objectives To obtain valid estimates of the association between body mass index (BMI) and mortality by using offspring BMI as an instrumental variable for own BMI. Design Cohort study based on record linkage, with 50 years of follow-up for mortality. Associations of offspring BMI with all cause and cause specific maternal and paternal mortality were estimated as hazard ratios per standard deviation of offspring BMI. Setting A large intergenerational prospective population based database covering the general population of Sweden. Participants More than one million Swedish parent-son pairs. Results The final dataset analysed contained information on 1 018 012 mother-son pairs (122 677 maternal deaths) and 1 004 617 father-son pairs (242 126 paternal deaths). For some causes of death, the patterns of associations between offspring BMI and mortality were similar to those seen for own BMI and mortality in previous studies. Parental mortality from diabetes, coronary heart disease, and kidney cancer had the strongest positive associations with offspring BMI (for example, hazard ratio (HR) for coronary heart disease per standard deviation increase in offspring BMI for mothers 1.15, 95% CI 1.14 to 1.17 and for fathers 1.10, 1.09 to 1.11). However, in contrast to the inverse association of own BMI with lung cancer and respiratory disease mortality seen in other studies, there was a positive association between offspring BMI and lung cancer mortality in mothers (1.12, 1.09 to 1.15) and fathers (1.03, 1.02 to 1.05) and between offspring BMI and respiratory mortality in mothers (1.05, 1.02 to 1.08) and fathers (1.02, 1.00 to 1.04). Associations of own BMI and offspring BMI with all cause, cardiovascular disease related, and non-cardiovascular disease related mortality were compared in a subset of father-son pairs (n=72 815). When offspring BMI was used as an instrumental variable for paternal BMI, the causal association between BMI and paternal cardiovascular disease mortality (HR per standard deviation of BMI 1.82, 95% CI 1.17 to 2.83) was stronger than that indicated by the directly observed association between own BMI and cardiovascular disease mortality (1.45, 1.31 to 1.61). Conclusions Use of offspring BMI as a predictor of own BMI, a technique that avoids problems of reverse causality, suggests that positive associations of BMI with all cause and cardiovascular mortality may be underestimated in conventional observational studies. Use of offspring BMI instead of own BMI in analyses of respiratory disease and lung cancer mortality, for which previous studies have reported consistent and strong inverse associations with own BMI, suggests that such studies have overstated the apparent adverse consequences of lower BMI with respect to these outcomes.
How Games Move Us - Emotion by Design

This is a renaissance moment for video games -- in the variety of genres they represent, and the range of emotional territory they cover. But how do games create emotion? In How Games Move Us, Katherine Isbister takes the reader on a timely and novel exploration of the design techniques that evoke strong emotions for players. She counters arguments that games are creating a generation of isolated, emotionally numb, antisocial loners. Games, Isbister shows us, can actually play a powerful role in creating empathy and other strong, positive emotional experiences; they reveal these qualities over time, through the act of playing. She offers a nuanced, systematic examination of exactly how games can influence emotion and social connection, with examples -- drawn from popular, indie, and art games -- that unpack the gamer's experience. Isbister describes choice and flow, two qualities that distinguish games from other media, and explains how game developers build upon these qualities using avatars, non-player characters, and character customization, in both solo and social play. She shows how designers use physical movement to enhance players' emotional experience, and examines long-distance networked play. She illustrates the use of these design methods with examples that range from Sony's Little Big Planet to the much-praised indie game Journey to art games like Brenda Romero's Train. Isbister's analysis shows us a new way to think about games, helping us appreciate them as an innovative and powerful medium for doing what film, literature, and other creative media do: helping us to understand ourselves and what it means to be human.
Tre1 GPCR initiates germ cell transepithelial migration by regulating Drosophila melanogaster E-cadherin

Despite significant progress in identifying the guidance pathways that control cell migration, how a cell starts to move within an intact organism, acquires motility, and loses contact with its neighbors is poorly understood. We show that activation of the G protein–coupled receptor (GPCR) trapped in endoderm 1 (Tre1) directs the redistribution of the G protein Gβ as well as adherens junction proteins and Rho guanosine triphosphatase from the cell periphery to the lagging tail of germ cells at the onset of Drosophila melanogaster germ cell migration. Subsequently, Tre1 activity triggers germ cell dispersal and orients them toward the midgut for directed transepithelial migration. A transition toward invasive migration is also a prerequisite for metastasis formation, which often correlates with down-regulation of adhesion proteins. We show that uniform down-regulation of E-cadherin causes germ cell dispersal but is not sufficient for transepithelial migration in the absence of Tre1. Our findings therefore suggest a new mechanism for GPCR function that links cell polarity, modulation of cell adhesion, and invasion.
New hepatitis C virus therapies: drug classes and metabolism, drug interactions relevant in the transplant settings, drug options in decompensated cirrhosis, and drug options in end-stage renal disease

Purpose of reviewThis article will review the new direct acting antiviral agent (DAA) drug classes for the treatment of hepatitis C, how they are combined and the relevant drug–drug interactions in the postliver transplant setting. Treatment options for chronic hepatitis C in patients with decompensated cirrhosis and end-stage renal disease will also be discussed. Recent findingsThe availability of new drug classes has increased the treatment options in patients with hepatitis C in the post-transplant settings. Clinical trials have concluded that sofosbuvir (SOF) with ledipasvir (LDV) may be safely administered with calcineurin inhibitors (tacrolimus, cyclosporine) and rapamycin inhibitors (sirolimus, everolimus). Similarly, paritaprevir/ritonavir, ombitasvir, and dasabuvir may be administered with tacrolimus and cyclosporine though appropriate dose adjustments must be made to the calcineurin inhibitors. In those with decompensated Childs B/C cirrhosis, SOF, SOF and LDV, as well as daclatasvir may be given without dose adjustment. In renal impairment, all DAAs may be used safely down to a glomerular filteration rate (GFR) of 30 ml/min. Simeprevir, paritaprevir, ombitasvir, and dasabuvir may be given for those down to GFR of 15 ml/min. Finally, daclatasvir may be given without dose administration change. SummaryIn summary, DAAs have better tolerability and greater efficacy than interferon-based therapy post-transplant. Drug–drug interactions must be carefully assessed when these newer agents are used for therapy in the postliver transplant settings. Thus far, dose adjustments for DAAs have not been required in chronic kidney disease though data are incomplete in those with severe chronic kidney disease (CKD) or on dialysis. Hepatitis C treatment in those with decompensated cirrhosis results in impaired hepatic metabolism that may affect DAA levels, and clinicians should carefully choose treatment options for Childs B and C cirrhotic patients.
Carotid plaque, a subclinical precursor of vascular events

Background: Carotid atherosclerosis is a known biomarker associated with future vascular disease. The risk associated with small, nonstenotic carotid plaques is less clear. The objective of this study was to examine the association between maximum carotid plaque thickness and risk of vascular events in an urban multiethnic cohort. Methods: As part of the population-based Northern Manhattan Study, carotid plaque was analyzed among 2,189 subjects. Maximum carotid plaque thickness was evaluated at the cutoff level of 1.9 mm, a prespecified value of the 75th percentile of the plaque thickness distribution. The primary outcome measure was combined vascular events (ischemic stroke, myocardial infarction, or vascular death). Results: Carotid plaque was present in 1,263 (58%) subjects. After a mean follow-up of 6.9 years, vascular events occurred among 319 subjects; 121 had fatal or nonfatal ischemic stroke, 118 had fatal or nonfatal myocardial infarction, and 166 died of vascular causes. Subjects with maximum carotid plaque thickness greater than 1.9 mm had a 2.8-fold increased risk of combined vascular events in comparison to the subjects without carotid plaque (hazard ratio, 2.80; 95% CI, 2.04–3.84). In fully adjusted models, this association was significant only among Hispanics. Approximately 44% of the low-risk individuals by Framingham risk score had a 10-year vascular risk of 18.3% if having carotid plaque. Conclusions: Maximum carotid plaque thickness is a simple and noninvasive marker of subclinical atherosclerosis associated with increased risk of vascular outcomes in a multiethnic cohort. Maximum carotid plaque thickness may be a simple and nonexpensive tool to assist with vascular risk stratification in preventive strategies and a surrogate endpoint in clinical trials.
PLANNING FOR ECONOMIC DIVERSIFICATION IN OMAN

This paper is not about the review and analysis of past diversification efforts, though main achievements will be briefly presented. It is not also about identifying the priority sectors that have the potential for diversification or about defining which strategy should Oman follows. The paper does not aim at identifying the reforms needed in the labour or Omanization policy and the kind of training programs to be implemented for skill development in order to achieve economic diversification.
Epstein-Barr Virus Isolates Retain Their Capacity To Evade T Cell Immunity through BNLF2a despite Extensive Sequence Variation

ABSTRACT The Epstein-Barr virus (EBV)-encoded immune evasion protein BNLF2a inhibits the transporter associated with antigen processing (TAP), thereby downregulating HLA class I expression at the cell surface. As a consequence, recognition of EBV-infected cells by cytotoxic T cells is impaired. Here, we show that sequence polymorphism of the BNLF2a protein is observed with natural EBV isolates, with evidence for positive selection. Despite these mutations, the BNLF2a variants efficiently reduce cell surface HLA class I levels. This conservation of BNLF2a function during evolution of EBV implies an important role for the viral TAP inhibitor in preventing T cell recognition during viral infection.