Miracle-dz/UniFAR-FTUs huggingface dataset:
Nationwide Experience of Treatment with Protease Inhibitors in Chronic Hepatitis C Patients in Denmark: Identification of Viral Resistance Mutations

Background and Aims The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting. Methods 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy. Results 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively. Conclusions The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response.
STRUCTURE DEVELOPMENT OF PP/PA6 BLENDS. INTERFACIAL MODIFICATIONS AND PRELIMINARY MODELING OF MACROSCOPIC PROPERTIES

Statistical experimental design following the Box-Wilson methodology has been used by the authors for years with the main goal to correlate ultimate properties (i.e., from the macroscopic scale) with those from the microscopic scale. The aim to obtain optimal performance from heterogeneous materials based on polymers, mainly polymer blends and composites, strongly depends on the phases of the morphology involved and then on the structure and properties of the interfaces. It is because of this fact that interfacial modification agents are usually present in polymer blends and composites. The present work deals with the role played by two interfacial agents—obtained in our laboratories—as interfacial modifiers in the polyamide 6/polypropylene (PA6/PP) binary system. An experimental Box-Wilson design with two independent variables (blend composition and amount of interfacial agent) was performed, with the dependent variables being the parameters obtained from tensile tests. Mechanical property model forecasts were confirmed by phase contrast optical microscopy. The micromechanical model proposed seems to agree with the Box-Wilson forecasts, which had analysis of variance (ANOVA) from models that were satisfactory for these purposes.
Is the Price System or Rationing More Effective in Getting a Commodity to Those Who Need It Most

Using a simple formal model, the present paper analyzes under what conditions the price system or crude rationing is more effective in matching up the limited supply of a deficit commodity with those users who need it most. The answer depends in a well-defined way on the distribution of needs and income. Other things being equal, the price system has greater comparative effectiveness in sorting out the deficit commodity and in getting it to those who need it most when wants are more widely dispersed or when the society is relatively egalitarian in its income distribution. Conversely, rationing is more effective as needs for the deficit commodity are more uniform or as there is greater income inequality.
Performance evaluation of a grid resource monitoring and discovery service

The Grid Information Service (GIS) is one of the Grid Common Services which make up the basic functions belonging to Grids. This service offers a resource discovery mechanism, of which an implementation is provided by the Monitoring and Discovery Service (MDS- 2) which is part of the Globus Toolkit. Grid applications are typically the users of this resource discovery mechanism; knowledge is thus obtained about the existence of appropriate resources on which to execute jobs. Since these Grid applications are likely to be influenced by dynamic middleware, it is crucial that they experience a reliable performance for the proper utilisation of resources and for accountability purposes. Consequently, the approach taken in this paper is to investigate and evaluate a level of performance obtainable from the MDS. A better understanding of the performance of the GRIS (Grid Resource Information Service) and subsequently the GIIS (Grid Index Information Service), leads to a more standard way of formalising the performance of a Grid Information Service. This is achieved by defining a number of performance metrics which are analysed against a set of different information gathering methods and GRIS back-end implementations.
On the Self-Regulation of Implicit and Explicit Prejudice

The present study identifies a broad taxonomy of motives underlying the desire to regulate prejudice and assess the impact of motivation to regulate prejudice on levels of explicit and implicit prejudice. Using self-determination theory as the foundation, six forms of motivation to regulate prejudice are proposed. In Study 1 (N = 257), an exploratory factor analysis reveals evidence for the six proposed dimensions. In Study 2 (N = 198), the six-factor taxonomy of motivation to regulate prejudice is further validated using a confirmatory factor analysis, and construct validity is obtained. In Study 3 (N = 62), motivation to regulate prejudice is manipulated before participants complete the Implicit Association Test (IAT) and explicit measures of prejudice. Results reveal that those with highly self-determined regulation of prejudice demonstrate lower implicit and explicit prejudice than their less self-determined counterparts. Results are discussed in terms of an increased understanding of the motivation to control prejudice.
GC analysis of human breath with a series-coupled column ensemble and a multibed sorption trap.

The combination of a tandem column ensemble and an on-line microsorption trap is used for the analysis of organic compounds in human breath samples. The four-bed sorption trap uses a series of discreet sorption beds containing three grades of graphitized carbon and a carbon molecular sieve to quantitatively remove most organic compounds from 0.8-L breath samples. The trap is then heated to 300 degrees C in approximately 1.5 s and maintained at this temperature for 10 s. The resulting vapor plug width is in the range 0.7-1.3 s for the compounds found in the breath samples. The separation is performed with a 15-m-long, 0.25-mm-i.d. capillary using a 0.5-microm-thick film of nonpolar dimethyl polysiloxane coupled in series to a polar column, either trifluoropropylmethyl polysiloxane or poly(ethylene glycol). Both column combinations are successful in separating the early-eluting compounds acetone, isoprene, pentane, methyl alcohol, and ethyl alcohol, which are all common in breath samples. The poly(ethylene glycol) combination gave better separation but showed relatively fast deterioration for repeated analysis of wet samples. Breath samples were obtained under different conditions (smoker, nonsmoker, gum chewer), and 25 compounds were identified in the various samples. Many additional peaks are observed but not identified. Analytical curves (log-log) of peak area versus sample volume for test compounds are linear in the range 80-800 cm3. Detection limits (3sigma) for several volatile compounds in 800-cm3 samples are in the 1-5 ppb range.
GC skew at the 5′ and 3′ ends of human genes links R-loop formation to epigenetic regulation and transcription termination

Strand asymmetry in the distribution of guanines and cytosines, measured by GC skew, predisposes DNA sequences toward R-loop formation upon transcription. Previous work revealed that GC skew and R-loop formation associate with a core set of unmethylated CpG island (CGI) promoters in the human genome. Here, we show that GC skew can distinguish four classes of promoters, including three types of CGI promoters, each associated with unique epigenetic and gene ontology signatures. In particular, we identify a strong and a weak class of CGI promoters and show that these loci are enriched in distinct chromosomal territories reflecting the intrinsic strength of their protection against DNA methylation. Interestingly, we show that strong CGI promoters are depleted from the X chromosome while weak CGIs are enriched, a property consistent with the acquisition of DNA methylation during dosage compensation. Furthermore, we identify a third class of CGI promoters based on its unique GC skew profile and show that this gene set is enriched for Polycomb group targets. Lastly, we show that nearly 2000 genes harbor GC skew at their 3′ ends and that these genes are preferentially located in gene-dense regions and tend to be closely arranged. Genomic profiling of R-loops accordingly showed that a large proportion of genes with terminal GC skew form R-loops at their 3′ ends, consistent with a role for these structures in permitting efficient transcription termination. Altogether, we show that GC skew and R-loop formation offer significant insights into the epigenetic regulation, genomic organization, and function of human genes.
Concise Review: Adipose‐Derived Stromal Vascular Fraction Cells and Stem Cells: Let's Not Get Lost in Translation

Subcutaneous fat has emerged as an alternative tissue source for stromal/stem cells in regenerative medicine. Over the past decade, international research efforts have established a wealth of basic science and preclinical evidence regarding the differentiation potential and regenerative properties of both freshly processed, heterogeneous stromal vascular fraction cells and culture expanded, relatively homogeneous adipose‐derived stromal/stem cells. The stage has been set for clinicians to translate adipose‐derived cells from the bench to the bedside; however, this process will involve “development” steps that fall outside of traditional “hypothesis‐driven, mechanism‐based” paradigm. This concise review examines the next stages of the development process for therapeutic applications of adipose‐derived cells and highlights the current state of the art regarding clinical trials. It is recommended that the experiments addressing these issues be reported comprehensively in the peer‐review literature. This transparency will accelerate the standardization and reproducibility of adipose‐derived cell therapies with respect to their efficacy and safety. STEM CELLS 2011;29:749–754
An Estimate of Managed Colony Losses in the Winter of 2006 - 2007: A Report Commissioned by the Apiary Inspectors of America

In an attempt to quantify the degree and extent of losses experienced in U.S. beekeeping operations between September 2006 and March 2007, members of the Apiary Inspectors of America (AIA) were asked to survey beekeepers who represent the hobby, sideline, and commercial beekeeping industries of their state. In all, 384 beekeeping operations were surveyed representing a total of 143,816 colonies plus 9,507 splits made between September and March. The total loss and average loss of bees in all operations was 31.8% and 37.6%, respectively. Of the surveyed beekeepers, 51.9% reported “abnormally heavy losses”; these beekeepers had a total loss of 55.4%, compared to the 15.9% total loss experienced by beekeepers who reported “normal losses”. Of responding beekeepers reporting the number of hives containing few or no bees in spring, 23.8% met the specified definition of Colony Collapse Disorder (CCD), meaning that 50% of their dead colonies were found without bees and/or with very few dead bees in the hive or apiary. CCD-suffering operations had a total loss of 45.0% compared to the total loss of 25.4% of all colonies experienced by nonCCD suffering beekeepers. Most hobbyist beekeepers believed that starvation was the leading cause of death in their colonies, while commercial beekeepers overwhelming believed invertebrate pests (Varroa mites, honey bee tracheal mites, and/or small hive beetles) were the leading cause of colony mortality. Considerable variability in losses and in the proportion of operations suffering from CCD was reported from the various states.
GPIHBP1 Missense Mutations Often Cause Multimerization of GPIHBP1 and Thereby Prevent Lipoprotein Lipase Binding

Rationale: GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1 missense mutations that interfere with LPL binding cause familial chylomicronemia. Objective: We sought to understand mechanisms by which GPIHBP1 mutations prevent LPL binding and lead to chylomicronemia. Methods and Results: We expressed mutant forms of GPIHBP1 in Chinese hamster ovary cells, rat and human endothelial cells, and Drosophila S2 cells. In each expression system, mutation of cysteines in GPIHBP1’s Ly6 domain (including mutants identified in patients with chylomicronemia) led to the formation of disulfide-linked dimers and multimers. GPIHBP1 dimerization/multimerization was not unique to cysteine mutations; mutations in other amino acid residues, including several associated with chylomicronemia, also led to protein dimerization/multimerization. The loss of GPIHBP1 monomers is relevant to the pathogenesis of chylomicronemia because only GPIHBP1 monomers—and not dimers or multimers—are capable of binding LPL. One GPIHBP1 mutant, GPIHBP1-W109S, had distinctive properties. GPIHBP1-W109S lacked the ability to bind LPL but had a reduced propensity for forming dimers or multimers, suggesting that W109 might play a more direct role in binding LPL. In support of that idea, replacing W109 with any of 8 other amino acids abolished LPL binding—and often did so without promoting the formation of dimers and multimers. Conclusions: Many amino acid substitutions in GPIHBP1’s Ly6 domain that abolish LPL binding lead to protein dimerization/multimerization. Dimerization/multimerization is relevant to disease pathogenesis, given that only GPIHBP1 monomers are capable of binding LPL.
Clinical Usefulness of Sonoelastography in Infants With Congenital Muscular Torticollis

Objective To evaluate the clinical usefulness of sonoelastography in infants with congenital muscular torticollis (CMT). Methods The medical records of 215 infants clinically diagnosed with CMT were retrospectively reviewed. Fifty-three infants met the inclusion criteria as follows: 1) infants diagnosed as CMT with a palpable neck mass before 3 months of age, 2) infants who were evaluated initially by both B-mode ultrasonography and sonoelastography, and 3) infants who had received physical therapy after being diagnosed with CMT. We checked the thickness of the sternocleidomastoid (SCM) muscles in B-mode ultrasonography, strain ratio of the SCM muscles in sonoelastography, and treatment duration. We evaluated the correlation between the treatment duration and the following factors: SCM muscle thickness, ratio of SCM muscle thickness on the affected to unaffected side (A/U ratio), and strain ratio. Results Both the thickness of the affected SCM muscle and the A/U ratio did not show significant correlation with the treatment duration (p=0.66, p=0.90). The strain ratio of the affected SCM muscle was significantly greater than that of the unaffected SCM muscle (p<0.001), and the strain ratio showed significant correlation with the treatment duration (p=0.001). Conclusion Sonoelastography may be a useful adjunctive tool to B-mode ultrasonography for evaluating infants with CMT, especially when predicting their rehabilitation outcomes.
Effect of two aerobic training regimens on the cardiorespiratory response of prepubertal boys and girls

The aim of this study was to examine the effect of two endurance training regimens of varying duration and frequency on maximal oxygen uptake (V̇O2max) of prepubertal boys and girls. The subjects consisted of 84 prepubertal children, aged 10–11 y. Two groups, EG1 (n= 36) and EG2 (n= 20), were involved in a 13 wk endurance training programme (intensity: higher than 80% of maximal heart rate for both groups; frequency: 3 and 2 sessions per week; duration: 25–35 min and 15–20 min per session in the target zone, for EG1 and EG2, respectively). Another group of 28 children served as a control group. Each subject performed a continuous and progressive exercise test to exhaustion on a cycle ergometer to evaluate V̇O2max before and after the 13 wk study period. The main findings of this study were: (i) there was no improvement in V̇O2max after a training programme with the following characteristics: 2 sessions per week with 15–20 min of exercise performed at an intensity higher than 80% of maximal heart rate; (ii) a V̇O2max enhancement (on average +7%) was seen only in children who participated in a training programme organized on the basis of three sessions per week during which exercise intensities higher than 80% of maximal heart rate were sustained for at least 25 min per session; and (iii) there was no gender difference in the training response.
Heat Waves and Climate Change: Applying the Health Belief Model to Identify Predictors of Risk Perception and Adaptive Behaviours in Adelaide, Australia

Heat waves are considered a health risk and they are likely to increase in frequency, intensity and duration as a consequence of climate change. The effects of heat waves on human health could be reduced if individuals recognise the risks and adopt healthy behaviours during a heat wave. The purpose of this study was to determine the predictors of risk perception using a heat wave scenario and identify the constructs of the health belief model that could predict adaptive behaviours during a heat wave. A cross-sectional study was conducted during the summer of 2012 among a sample of persons aged between 30 to 69 years in Adelaide. Participants’ perceptions were assessed using the health belief model as a conceptual frame. Their knowledge about heat waves and adaptive behaviours during heat waves was also assessed. Logistic regression analyses were performed to determine the predictors of risk perception to a heat wave scenario and adaptive behaviours during a heat wave. Of the 267 participants, about half (50.9%) had a high risk perception to heat waves while 82.8% had good adaptive behaviours during a heat wave. Multivariate models found that age was a significant predictor of risk perception. In addition, participants who were married (OR = 0.21; 95% CI, 0.07–0.62), who earned a gross annual household income of ≥$60,000 (OR = 0.41; 95% CI, 0.17–0.94) and without a fan (OR = 0.29; 95% CI, 0.11–0.79) were less likely to have a high risk perception to heat waves. Those who were living with others (OR = 2.87; 95% CI, 1.19–6.90) were more likely to have a high risk perception to heat waves. On the other hand, participants with a high perceived benefit (OR = 2.14; 95% CI, 1.00–4.58), a high “cues to action” (OR = 3.71; 95% CI, 1.63–8.43), who had additional training or education after high school (OR = 2.65; 95% CI, 1.25–5.58) and who earned a gross annual household income of ≥$60,000 (OR = 2.66; 95% CI, 1.07–6.56) were more likely to have good adaptive behaviours during a heat wave. The health belief model could be useful to guide the design and implementation of interventions to promote adaptive behaviours during heat waves.
A Retrospective 30 Years After Discovery of the Enhanced Permeability and Retention Effect of Solid Tumors: Next‐Generation Chemotherapeutics and Photodynamic Therapy—Problems, Solutions, and Prospects

Solid tumor has unique vascular architecture, excessive production of vascular mediators, and extravasation of macromolecules from blood vessels into the tumor tissue interstitium. These features comprise the phenomenon named the EPR effect of solid tumors, described in 1986. Our investigations on the EPR revealed that many mediators, such as bradykinin, NO, and prostaglandins, are involved in the EPR effect, which is now believed to be the most important element for cancer‐selective drug delivery. However, tumors in vivo manifest great diversity, and some demonstrate a poor EPR effect, for example, because of impaired vascular flow involving thrombosis, with poor drug delivery and therapeutic failure. Another important element of this effect is that it operates in metastatic cancers. Because few drugs are currently effective against metastases, the EPR effect offers a great advantage in nanomedicine therapy. The EPR effect can also be augmented two to three times via nitroglycerin, ACE inhibitors, and angiotensin II‐induced hypertension. The delivery of nanomedicines to tumors can thereby be enhanced. In traditional PDT, most PSs had low MW and little tumor‐selective accumulation. Our hydroxypropylmetacrylamide‐polymer‐conjugated‐PS, zinc protoporphyrin (apparent MW >50 kDa) showed tumor‐selective accumulation, as revealed by fluorescent imaging of autochthonous cancers. After one i.v. injection of polymeric PS followed by two or three xenon light irradiation/treatments, most tumors regressed. Thus, nanoprobes with the EPR effect seem to have remarkable effects. Enhancing the EPR effect by using vascular modulators will aid innovations in PDT for greater tumor‐targeted drug delivery.
Chemical-Reaction-Inspired Metaheuristic for Optimization

We encounter optimization problems in our daily lives and in various research domains. Some of them are so hard that we can, at best, approximate the best solutions with (meta-) heuristic methods. However, the huge number of optimization problems and the small number of generally acknowledged methods mean that more metaheuristics are needed to fill the gap. We propose a new metaheuristic, called chemical reaction optimization (CRO), to solve optimization problems. It mimics the interactions of molecules in a chemical reaction to reach a low energy stable state. We tested the performance of CRO with three nondeterministic polynomial-time hard combinatorial optimization problems. Two of them were traditional benchmark problems and the other was a real-world problem. Simulation results showed that CRO is very competitive with the few existing successful metaheuristics, having outperformed them in some cases, and CRO achieved the best performance in the real-world problem. Moreover, with the No-Free-Lunch theorem, CRO must have equal performance as the others on average, but it can outperform all other metaheuristics when matched to the right problem type. Therefore, it provides a new approach for solving optimization problems. CRO may potentially solve those problems which may not be solvable with the few generally acknowledged approaches.