Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization and stability studies of a novel liposomal cyclosporin A prepared using the supercritical fluid method: comparison with the modified conventional Bangham method

A novel method to prepare cyclosporin A encapsulated liposomes was introduced using supercritical fluid of carbon dioxide (SCF-CO2) as an antisolvent. To investigate the strength of the newly developed SCF-CO2 method compared with the modified conventional Bangham method, particle size, zeta potential, and polydispersity index (PDI) of both liposomal formulations were characterized and compared. In addition, entrapment efficiency (EE) and drug loading (DL) characteristics were analyzed by reversed-phase high-performance liquid chromatography. Significantly larger particle size and PDI were revealed from the conventional method, while EE (%) and DL (%) did not exhibit any significant differences. The SCF-CO2 liposomes were found to be relatively smaller, multilamellar, and spherical with a smoother surface as determined by transmission electron microscopy. SCF-CO2 liposomes showed no significant differences in their particle size and PDI after more than 3 months, whereas conventional liposomes exhibited significant changes in their particle size. The initial yield (%), EE (%), and DL (%) of SCF-CO2 liposomes and conventional liposomes were 90.98 ± 2.94, 92.20 ± 1.36, 20.99 ± 0.84 and 90.72 ± 2.83, 90.24 ± 1.37, 20.47 ± 0.94, respectively, which changed after 14 weeks to 86.65 ± 0.30, 87.63 ± 0.72, 18.98 ± 0.22 and 75.04 ± 8.80, 84.59 ± 5.13, 15.94 ± 2.80, respectively. Therefore, the newly developed SCF-CO2 method could be a better alternative compared with the conventional method and may provide a promising approach for large-scale production of liposomes.
Critical review of NGS analyses for de novo genotyping multigene families

The genotyping of highly polymorphic multigene families across many individuals used to be a particularly challenging task because of methodological limitations associated with traditional approaches. Next‐generation sequencing (NGS) can overcome most of these limitations, and it is increasingly being applied in population genetic studies of multigene families. Here, we critically review NGS bioinformatic approaches that have been used to genotype the major histocompatibility complex (MHC) immune genes, and we discuss how the significant advances made in this field are applicable to population genetic studies of gene families. Increasingly, approaches are introduced that apply thresholds of sequencing depth and sequence similarity to separate alleles from methodological artefacts. We explain why these approaches are particularly sensitive to methodological biases by violating fundamental genotyping assumptions. An alternative strategy that utilizes ultra‐deep sequencing (hundreds to thousands of sequences per amplicon) to reconstruct genotypes and applies statistical methods on the sequencing depth to separate alleles from artefacts appears to be more robust. Importantly, the ‘degree of change’ (DOC) method avoids using arbitrary cut‐off thresholds by looking for statistical boundaries between the sequencing depth for alleles and artefacts, and hence, it is entirely repeatable across studies. Although the advances made in generating NGS data are still far ahead of our ability to perform reliable processing, analysis and interpretation, the community is developing statistically rigorous protocols that will allow us to address novel questions in evolution, ecology and genetics of multigene families. Future developments in third‐generation single molecule sequencing may potentially help overcome problems that still persist in de novo multigene amplicon genotyping when using current second‐generation sequencing approaches.
Disulfide Bond Formation in Secreton Component PulK Provides a Possible Explanation for the Role of DsbA in Pullulanase Secretion

ABSTRACT When expressed in Escherichia coli, the 15Klebsiella oxytoca pul genes that encode the so-called Pul secreton or type II secretion machinery promote pullulanase secretion and the assembly of one of the secreton components, PulG, into pili. Besides these pul genes, efficient pullulanase secretion also requires the host dsbA gene, encoding a periplasmic disulfide oxidoreductase, independently of disulfide bond formation in pullulanase itself. Two secreton components, the secretin pilot protein PulS and the minor pseudopilin PulK, were each shown to posses an intramolecular disulfide bond whose formation was catalyzed by DsbA. PulS was apparently destabilized by the absence of its disulfide bond, whereas PulK stability was not dramatically affected either by adsbA mutation or by the removal of one of its cysteines. The pullulanase secretion defect in a dsbA mutant was rectified by overproduction of PulK, indicating reduced disulfide bond formation in PulK as the major cause of the secretion defect under the conditions tested (in which PulS is probably present in considerable excess of requirements). PulG pilus formation was independent of DsbA, probably because PulK is not needed for piliation.
Three-dimensional reconstruction of the "bright ring" echogenicity from porcine blood upstream in a stenosed tube

To investigate the echogenicity variation due to blood flow disturbance near a stenosis under pulsatile flow, a series of in vitro experiments were performed in a rigid tube with an eccentric stenosis of 70% area reduction in a mock flow loop. An ultrasonic B-mode with a Doppler spectrogram was used to correlate echogenicity with flow speed and stroke rate. This paper reports echogenicity variation upstream of a stenosis under pulsatile flow. The experimental results showed that blood flow disturbed by the stenosis affects echogenicity and red blood cell rouleaux upstream. A hypoechoic ldquoblack holerdquo was shown at the center of the stream at systole. During diastole, the ldquobright ringrdquo in cross-sectional images was observed as eddy-like or parabolic profiles in longitudinal images. These images could be reconstructed into a 3-dimensional animation, providing a better understanding of dynamic changes of the rouleaux distribution upstream of a stenosis under pulsatile flow.
Self-reported post-operative recovery in children: development of an instrument.

RATIONALE, AIMS AND OBJECTIVES According to the United Nations (1989), children have the right to be heard and to have their opinions respected. Since post-operative recovery is an individual and subjective experience and patient-reported outcome measures are considered important, our aim was to develop and test an instrument to measure self-reported quality of recovery in children after surgical procedures. METHODS Development of the instrument Postoperative Recovery in Children (PRiC) was influenced by the Quality of Recovery-24, for use in adults. Eighteen children and nine professionals validated the items with respect to content and language. A photo questionnaire was developed to determine whether the children's participation would increase compared with the text questionnaire. The final instrument was distributed consecutively to 390 children, ages 4-12 years, who underwent tonsil surgery at four hospitals in Sweden. RESULTS A total of 238 children with a mean age of 6.5 years participated. According to the parents, 23% circled the answers themselves and 59% participated to a significant degree. However, there was no significant difference in participation between those who received a photo versus a text questionnaire. Psychometric tests of the instrument showed that Cronbach's alpha for the total instrument was 0.83 and the item-total correlations for 22 of the items were ≥0.20. CONCLUSION Our results support use of the PRiC instrument to assess and follow-up on children's self-reported post-operative recovery after tonsil operation, both in clinical praxis as well in research.
A Quasi Experiment to Assess the Consumer and Informational Determinants of Nutrition Information Processing Activities: The Case of the Nutrition Labeling and Education Act

The author reports a longitudinal quasi experiment that uses the implementation of the Nutrition Labeling and Education Act (NLEA) to examine the consumer and information determinants of nutrition information processing activities. Over 1000 consumers from balanced demographic, geographic, and site categories and across 20 different product categories were observed and surveyed within a supermarket setting. Findings suggest that consumers acquired and comprehended more nutrition information following the introduction of the new labels. The NLEA did not, however, always influence these outcomes irrespective of individual consumer differences. Specifically, the new nutrition labels were comprehensible to consumers with varying levels of motivation and most types of nutrition knowledge. However, the new labels appeared to widen consumer differences in terms of how much nutrition information was actually acquired—more motivated consumers and less skeptical consumers acquired more information after the NLEA was passed. Finally, consistent with the NLEA's apparent ability to reduce comprehension differences, the new labels narrowed comprehension differences across healthy and unhealthy products. In contrast, the NLEA widened differences in nutrition information acquisition in favor of unhealthy product categories. These results have implications for public health gains, as well as for the degree to which nutrition may become the basis for competition in unhealthy product categories.
Impaired mesenchymal stem cell differentiation and osteoclastogenesis in mice deficient for Igf2-P2 transcripts

During embryonic development, Igf2 gene transcription is highly regulated through the use of several promoters whose specific roles are not defined. Here, we show that loss-of-function of one of these promoters, Igf2-P2, results in growth defects that are temporally and quantitatively different from those seen in Igf2-null mutants. In particular, Igf2-P2 mutants exhibit skeletal abnormalities characterized by thin and short bones with reduced mineralization and medullar cavity and with altered bone remodeling. These abnormalities are associated with decreased numbers of embryonic mesenchymal chondroprogenitors, adult mesenchymal stem cells and osteoprogenitors. Differentiation of osteoprogenitors into osteoblasts is impaired in the Igf2-P2 mutant mice in a cell-autonomous manner, and osteopontin is a target of the IGF2 signaling pathway during this differentiation. Igf2-P2 mutant mice also display impaired formation of giant osteoclasts owing to a defective micro-environment. These results support a model wherein transcriptional activity of the Igf2-P2 promoter regulates the fate of mesenchymal progenitors during bone development and remodeling in the adult, and regulates osteogenesis in a cell-autonomous and non-autonomous manner.
Bilingual Experiments with an Arabic-English Corpus for Opinion Mining

Recently, Opinion Mining (OM) is receiving more attention due to the abundance of forums, blogs, ecommerce web sites, news reports and additional web sources where people tend to express their opinions. There are a number of works about Sentiment Analysis (SA) studying the task of identifying the polarity, whether the opinion expressed in a text is positive or negative about a given topic. However, most of research is focused on English texts and there are very few resources for other languages. In this work we present an Opinion Corpus for Arabic (OCA) composed of Arabic reviews extracted from specialized web pages related to movies and films using this language. Moreover, we have translated the OCA corpus into English, generating the EVOCA corpus (English Version of OCA). In the experiments carried out in this work we have used different machine learning algorithms to classify the polarity in these corpora showing that, although the experiments with EVOCA are worse than OCA, the results are comparable with other English experiments, since the loss of precision due to the translation is very slight.
Classification based hypothesis testing in neuroscience: Below‐chance level classification rates and overlooked statistical properties of linear parametric classifiers

Multivariate pattern analysis (MVPA) has recently become a popular tool for data analysis. Often, classification accuracy as quantified by correct classification rate (CCR) is used to illustrate the size of the effect under investigation. However, we show that in low sample size (LSS), low effect size (LES) data, which is typical in neuroscience, the distribution of CCRs from cross‐validation of linear MVPA is asymmetric and can show classification rates considerably below what would be expected from chance classification. Conversely, the mode of the distribution in these cases is above expected chance levels, leading to a spuriously high number of above chance CCRs. This unexpected distribution has strong implications when using MVPA for hypothesis testing. Our analyses warrant the conclusion that CCRs do not well reflect the size of the effect under investigation. Moreover, the skewness of the null‐distribution precludes the use of many standard parametric tests to assess significance of CCRs. We propose that MVPA results should be reported in terms of P values, which are estimated using randomization tests. Also, our results show that cross‐validation procedures using a low number of folds, e.g. twofold, are generally more sensitive, even though the average CCRs are often considerably lower than those obtained using a higher number of folds. Hum Brain Mapp 37:1842–1855, 2016. © 2016 Wiley Periodicals, Inc.
A single-institution phase II trial of five fractions of radiotherapy followed by four courses of FOLFOX chemotherapy as preoperative therapy for rectal adenocarcinoma.

553 Background: Preoperative radiotherapy (RT) with 5FU chemotherapy (CT) is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents have resulted in increased morbidity with little benefit. We evaluate a template that seeks to (1) include the known benefits of preoperative RT on local response/control, (2) provide for preoperative multi-drug CT, (3) avoid the morbidity of concurrent RT and multi-drug CT. METHODS Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for surgery, provided the response was sufficient. Preoperative treatment was 5 fractions RT (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of mFOLFOX6. Postoperative CT was at the discretion of the medical oncologist. The principal objectives are to demonstrate that this regimen can achieve T stage down staging (ypT < cT) and acute grade 3+ gastrointestinal (GI) morbidity equal to or better than historical controls. RESULTS Accrual opened late 2009, with 60 patients enrolled through 8/2011. Forty-six have had sufficient time to proceed to surgery with 4 having grade 3 preoperative GI morbidity. Two cases are inevaluable for response: one withdrew consent prior to CT and one received no surgery due to progression of cM1 disease (with local response). The 44 evaluable cases included 4 cT4 and 40 cT3; 32 (73%) cN+, 4 cM1. At surgery 33 (75%) had ypT0-2 residual disease including 13 (30%) ypT0, 14 (32%) were ypN+. Cases were sub-analyzed by whether disease was too advanced for the upcoming ACOSOG preoperative FOLFOX vs. 5FU-RT trial. By ACOSOG eligibility, response rates were (eligible first, ineligible second) ypT0: 10/22 (45%) vs. 3/22 (14%) (p = 0.05), ypT0-2: 19/22 (86%) vs. 14/22 (64%) (p = NS). CONCLUSIONS This regimen achieves high response rates with acceptable morbidity. The response for ACOSOG eligible cases meets pre-determined stopping criteria for proceeding to a randomized trial. Our successor study will randomize to this regimen vs. FOLFOX alone for ACOSOG eligible cases, while initially continuing as a single arm trial for ACOSOG ineligible cases.
Energy-Efficient Cluster-Based Service Discovery in Wireless Sensor Networks

We propose an energy-efficient service discovery protocol for wireless sensor networks. Our solution exploits a cluster overlay, where the clusterhead nodes form a distributed service registry. A service lookup results in visiting only the clusterhead nodes. We aim for minimizing the communication costs during discovery of services and maintenance of a functional distributed service registry. We compare theoretically and by simulation the impact of the chosen clustering algorithm on the service discovery protocol
Suspended sediment yield estimation using genetic algorithm-based artificial intelligence models: case study of Mahanadi River, India

ABSTRACT The estimation of sediment yield is important in design, planning and management of river systems. Unfortunately, its accurate estimation using traditional methods is difficult as it involves various complex processes and variables. This investigation deals with a hybrid approach which comprises genetic algorithm-based artificial intelligence (GA-AI) models for the prediction of sediment yield in the Mahanadi River basin, India. Artificial neural network (ANN) and support vector machine (SVM) models are developed for sediment yield prediction, where all parameters associated with the models are optimized using genetic algorithms simultaneously. Water discharge, rainfall and temperature are used as input to develop the GA-AI models. The performance of the GA-AI models is compared to that of traditional AI models (ANN and SVM), multiple linear regression (MLR) and sediment rating curve (SRC) method for evaluating the predictive capability of the models. The results suggest that GA-AI models exhibit better performance than other models.
Lethal mutagenesis and evolutionary epidemiology

The lethal mutagenesis hypothesis states that within-host populations of pathogens can be driven to extinction when the load of deleterious mutations is artificially increased with a mutagen, and becomes too high for the population to be maintained. Although chemical mutagens have been shown to lead to important reductions in viral titres for a wide variety of RNA viruses, the theoretical underpinnings of this process are still not clearly established. A few recent models sought to describe lethal mutagenesis but they often relied on restrictive assumptions. We extend this earlier work in two novel directions. First, we derive the dynamics of the genetic load in a multivariate Gaussian fitness landscape akin to classical quantitative genetics models. This fitness landscape yields a continuous distribution of mutation effects on fitness, ranging from deleterious to beneficial (i.e. compensatory) mutations. We also include an additional class of lethal mutations. Second, we couple this evolutionary model with an epidemiological model accounting for the within-host dynamics of the pathogen. We derive the epidemiological and evolutionary equilibrium of the system. At this equilibrium, the density of the pathogen is expected to decrease linearly with the genomic mutation rate U. We also provide a simple expression for the critical mutation rate leading to extinction. Stochastic simulations show that these predictions are accurate for a broad range of parameter values. As they depend on a small set of measurable epidemiological and evolutionary parameters, we used available information on several viruses to make quantitative and testable predictions on critical mutation rates. In the light of this model, we discuss the feasibility of lethal mutagenesis as an efficient therapeutic strategy.
Study of waves observed in the equatorial ionospheric valley region using Jicamarca ISR and VIPIR ionosonde

Incoherent scatter (IS) radar and ionosonde (VIPIR, vertical incidence pulsed ionospheric radar) data were taken concurrently at Jicamarca during campaigns of January, April, June, and July 2015, January 2016, and most recently April 2017 to bring more insight into the state and dynamics of the ionospheric E-F valley region and the 150-km radar echoes detected from this region. To better understand the rich and dynamic vertical structure of 150-km echoes observed at the Jicamarca Radio Observatory (JRO) and other equatorial stations and to contribute to the understanding of the physics of this region, we used JRO ISR and VIPIR ionosonde techniques to perform high spatial and temporal resolution measurements. We found correlations between VHF backscatter radar measurements and fluctuations detected with the VIPIR ionosonde, which is an indication of gravity waves playing a role in modulating the space-time structure of the 150-km echoes. Fluctuations with periods from 5 to 15 minutes are observed in VIPIR ionograms as well as in the layers found in the 50 MHz radar range-time-intensity (RTI) plots. The quiet-time stratified electron density contours are being rippled by waves propagating through the ionosphere. Evidence for this is the fluctuation of virtual reflection heights and angle of arrival (AOA) of the ionosonde echoes. The AOA is provided by interferometry, which indicates that the echo is not always coming from overhead. Scatter plots of the AOA in the receiving antenna’s orthogonal baselines give us the propagation direction. Plots of virtual height
Genome-Wide Analysis of PDZ Domain Binding Reveals Inherent Functional Overlap within the PDZ Interaction Network

Binding selectivity and cross-reactivity within one of the largest and most abundant interaction domain families, the PDZ family, has long been enigmatic. The complete human PDZ domain complement (the PDZome) consists of 267 domains and we applied here a Bayesian selectivity model to predict hundreds of human PDZ domain interactions, using target sequences of 22,997 non-redundant proteins. Subsequent analysis of these binding scores shows that PDZs can be divided into two genome-wide clusters that coincide well with the division between canonical class 1 and 2 PDZs. Within the class 1 PDZs we observed binding overlap at unprecedented levels, mediated by two residues at positions 1 and 5 of the second α-helix of the binding pocket. Eight PDZ domains were subsequently selected for experimental binding studies and to verify the basics of our predictions. Overall, the PDZ domain class 1 cross-reactivity identified here implies that auxiliary mechanisms must be in place to overcome this inherent functional overlap and to minimize cross-selectivity within the living cell. Indeed, when we superimpose PDZ domain binding affinities with gene ontologies, network topology data and the domain position within a PDZ superfamily protein, functional overlap is minimized and PDZ domains position optimally in the binding space. We therefore propose that PDZ domain selectivity is achieved through cellular context rather than inherent binding specificity.