Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method

Background Low drug entrapment efficiency of hydrophilic drugs into poly(lactic-co-glycolic acid) (PLGA) nanoparticles is a major drawback. The objective of this work was to investigate different methods of producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections. Methods Different methods, such as single and double solvent evaporation emulsion, ion pairing, and nanoprecipitation were used to prepare both PLGA and PEGylated PLGA nanoparticles. The resulting nanoparticles were analyzed for their morphology, particle size and size distribution, drug loading and entrapment efficiency, thermal properties, and antibacterial activity. Results The nanoparticles prepared in this study were spherical, with an average particle size of 85–424 nm. The entrapment efficiency of the nanoparticles prepared using different methods was as follows: solid/oil/water ion pairing (29.9%) > oil/oil (5.5%) > water/oil/water (4.7%) > modified oil/water (4.1%) > nano precipitation (0.8%). Addition of dextran sulfate as an ion pairing agent, acting as an ionic spacer between PEGylated PLGA and minocycline, decreased the water solubility of minocycline, hence increasing the drug entrapment efficiency. Entrapment efficiency was also increased when low molecular weight PLGA and high molecular weight dextran sulfate was used. Drug release studies performed in phosphate buffer at pH 7.4 indicated slow release of minocycline from 3 days to several weeks. On antibacterial analysis, the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles was at least two times lower than that of the free drug. Conclusion Novel minocycline-PEGylated PLGA nanoparticles prepared by the ion pairing method had the best drug loading and entrapment efficiency compared with other prepared nanoparticles. They also showed higher in vitro antibacterial activity than the free drug.
Experimental Challenges in Studying Hydrogen Absorption in Ultrasmall Metal Nanoparticles

Recent advances on synthesis, characterisation and hydrogen absorption properties of ultra-small metal nanoparticles (defined here as objects with average size ≤ 3 nm) are briefly reviewed in the first part of this work. The experimental challenges encountered in performing accurate measurements of hydrogen absorption in Mg- and noble metal-based ultra-small nanoparticles are addressed. The second part of this work reports original results obtained for ultra-small bulk immiscible Pd-Rh nanoparticles. Carbon supported Pd-Rh nanoalloys in the whole binary chemical composition range have been successfully prepared by liquid impregnation method followed by reduction at 300 °C. EXAFS investigations suggested that the local structure of these nanoalloys is partially segregated into Rh-rich core and Pd-rich surface coexisting within the same nanoparticles. Downsizing to ultra-small dimensions completely suppresses the hydride formation in Pd-rich nanoalloys at ambient conditions, contrary to bulk and larger nanosized (5-6 nm) counterparts. The ultra-small Pd90Rh10 nanoalloy can absorb hydrogen forming solid solutions under these conditions, as suggested by in situ XRD. Apart from this composition, common laboratory techniques such as, in situ XRD, DSC and PCI failed to clarify the hydrogen interaction mechanism : either adsorption on developed surfaces or both adsorption and absorption with formation of solid solutions. Concluding insights were brought by in situ EXAFS experiments at synchrotron: ultra-small Pd75Rh25 and Pd50Rh50 nanoalloys absorb hydrogen forming solid solutions at ambient conditions. Moreover, the hydrogen solubility in these solid solutions is higher with increasing Pd content and this trend can be understood in terms of hydrogen preferential occupation in the Pd-rich regions, as suggested by in situ EXAFS. The Rh-rich nanoalloys (Pd25Rh75 and Pd10Rh90) only adsorb hydrogen on the developed surface of ultra-small nanoparticles. In summary, in situ characterization techniques carried out at large scale facilities are unique and powerful tools for in-depth investigation of hydrogen interaction with ultra-small nanoparticles at local level.
Multi-parameter single-cell kinetic analysis reveals multiple modes of cell death in primary pancreatic &bgr;-cells

Summary Programmed &bgr;-cell death plays an important role in both type 1 and type 2 diabetes. Most of what is known about the mechanisms of &bgr;-cell death comes from single time-point, single parameter measurements of bulk populations of mixed cells. Such approaches are inadequate for determining the true extent of the heterogeneity in death mechanisms. Here, we characterized the timing and order of molecular events associated with cell death in single &bgr;-cells under multiple diabetic stress conditions, including hyperglycemia, cytokine exposure, nutrient deprivation and endoplasmic reticulum (ER) stress. We simultaneously measured the kinetics of six distinct cell death mechanisms by using a caspase-3 sensor and three vital dyes, together with brightfield imaging. We identified several cell death modes where the order of events that usually define apoptosis were not observed. This we termed ‘partial apoptosis’. Remarkably, complete classical apoptosis, defined as cells with plasma membrane blebbing, caspase-3 activity, nuclear condensation and membrane annexin V labeling prior to loss of plasma membrane integrity, was found in only half of the cytokine-treated primary &bgr;-cells and never in cells stressed by serum removal. By contrast, in the MIN6 cell line, death occurred almost exclusively through complete classical apoptosis. Ambient glucose modulated the cell death mode and kinetics in primary &bgr;-cells. Taken together, our data define the kinetic progression of &bgr;-cell death mechanisms under different conditions and illustrate the heterogeneity and plasticity of cell death modes in &bgr;-cells. We conclude that apoptosis is not the primary mode of adult primary &bgr;-cell death.
Unit resection of buccal squamous cell carcinoma: Description of a new surgical technique

This study characterized the infiltration of primary tumors along the muscles, fascia and spaces of the maxillofacial region in buccal squamous cell carcinoma (BSCC) and suggested a new surgical strategy that is suitable for most stages. Based on the anatomic characteristics and infiltration of the primary tumor a new surgical approach - unit resection buccal surgery (URBS) - was developed. We evaluated this new surgical strategy, across a cohort of 127 BSCCs: 60 cases treated with URBS and 67 cases treated with conventional surgery. Notably there was no statistical difference in the clinicopathological variables between the two groups. After initial treatment with curative intent, the patients were regularly followed-up with clinical examination and imaging. URBS proved suitable for almost all stages of BSCC, and was particularly advantageous for advanced stages of BSCC. At 2 years post-treatment, the rates of overall survival were 83.3% in the URBS group and 60.1% in the conventional surgery group, respectively (hazard ratio 0.38; 95% CI 0.20 to 0.75; P=0.005). Similarly, the rates of disease-free survival were 76.6% and 51.9% in the URBS group and the conventional surgery group, respectively (hazard ratio 0.42; 95% CI 0.23 to 0.75; P=0.003). The principles of URBS are suitable for almost all stages of BSCC, especially advanced stages. URBS may improve the prognosis of BSCC patients.
T-Drive: Enhancing Driving Directions with Taxi Drivers' Intelligence

This paper presents a smart driving direction system leveraging the intelligence of experienced drivers. In this system, GPS-equipped taxis are employed as mobile sensors probing the traffic rhythm of a city and taxi drivers' intelligence in choosing driving directions in the physical world. We propose a time-dependent landmark graph to model the dynamic traffic pattern as well as the intelligence of experienced drivers so as to provide a user with the practically fastest route to a given destination at a given departure time. Then, a Variance-Entropy-Based Clustering approach is devised to estimate the distribution of travel time between two landmarks in different time slots. Based on this graph, we design a two-stage routing algorithm to compute the practically fastest and customized route for end users. We build our system based on a real-world trajectory data set generated by over 33,000 taxis in a period of three months, and evaluate the system by conducting both synthetic experiments and in-the-field evaluations. As a result, 60-70 percent of the routes suggested by our method are faster than the competing methods, and 20 percent of the routes share the same results. On average, 50 percent of our routes are at least 20 percent faster than the competing approaches.
The CLE Urdu POS Tagset

The paper presents a design schema and details of a new Urdu POS tagset. This tagset is designed due to challenges encountered in working with existing tagsets for Urdu. It uses tags that judiciously incorporate information about special morpho-syntactic categories found in Urdu. With respect to the overall naming schema and the basic divisions, the tagset draws on the Penn Treebank and a Common Tagset for Indian Languages. The resulting CLE Urdu POS Tagset consists of 12 major categories with subdivisions, resulting in 32 tags. The tagset has been used to tag 100k words of the CLE Urdu Digest Corpus, giving a tagging accuracy of 96.8%.
A Stochastic Fluid Flow Model of the Operation and Maintenance of Power Generation Systems

A tool to inform strategic decision making on electricity market bidding prices, based on prediction of long-term system operation, degradation, and maintenance, is described. The operation and maintenance of a hydro-power generation system is modeled using a bounded stochastic fluid flow model with special behavior at the boundaries. The stationary distribution for the model and useful time-dependent performance measures are derived. The application potential of the model is illustrated through a practical industry-derived example modeling the operation of a hydro-power generator, in which a number of operation strategies are compared using several performance measures.
Population Specific Impact of Genetic Variants in KCNJ11 Gene to Type 2 Diabetes: A Case-Control and Meta-Analysis Study

Background and Objectives Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis. Methods A case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95% confidence interval (CI) was used to assess the association strength. Cochran's Q, I2 statistics were used to study heterogeneity between the eligible studies. Results KCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P = 0.04) and higher body mass index (BMI) (P = 0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR = 0.98, 95% CI = 0.83–1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians. Conclusion KCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups.
Pyrimidinoceptor‐mediated activation of phospholipase C and phospholipase A2 in RAW 264.7 macrophages

1 As well as the presence of P2Z purinoceptors previously found in macrophages, we identified pyrimidinoceptors in RAW 264.7 cells, which activate phospholipase C (PLC) and phospholipase A2 (PLA2). 2 The relative potency of agonists to stimulate inositol phosphate (IP) formation and arachidonic acid (AA) release was UTP = UDP >> ATP, ATPγS, 2MeSATP. For both signalling pathways, the EC50 values for UTP and UDP (3 μm) were significantly lower than that for ATP and all other analogues tested (> 100 μm). 3 UTP and UDP displayed no additivity in terms of IP formation and AA release at maximally effective concentrations. 4 UTP‐, but not ATP‐, evoked AA release was 60% inhibited by pertussis toxin (PTX), while stimulation of IP formation by both agonists was unaffected. Short‐term treatment with phorbol 12‐myristate 13‐acetate (PMA) led to a dose‐dependent inhibition of IP responses to UTP and UDP, but failed to affect the AA responses. Removal of extracellular Ca2+ inhibited the PI response to UTP, but abolished its AA response. 5 ATP‐induction of these two transmembrane signal pathways was decreased in high Mg2+‐containing medium but potentiated by the removal of extracellular Mg2+. 6 Suramin and reactive blue displayed equal potency to inhibit the IP responses of UTP and ATP. 7 Both UTP and UDP (0.1–100 μm) induced a sustained increase in [Ca2+]i which lasted for more than 10 min. 8 Taken together, these results indicate that in mouse RAW 264.7 macrophages, pyrimidinoceptors with specificity for UTP and UDP mediate the activation of PLC and cytosolic (c) PLA2. The activation of PLC is via a PTX‐insensitive G protein, whereas that of cPLA2 is via a PTX‐sensitive G protein‐dependent pathway. The sustained Ca2+ influx caused by UTP contributes to the activation of cPLA2. RAW 264.7 cells also possess P2Z purinoceptors which mediate ATP4‐‐induced PLC and PLA2 activation.
Immigration, Language, and Education: How Does Language Policy Structure Opportunity?

Background/Context According to U.S. Census figures, 11 million elementary and secondary students of immigrant families were enrolled in the public schools in October 2005, representing 20% of all students, and this figure is expected to grow in the coming years. Most of these students enter school as English learners (ELs), and most ELs have exceptionally low performance on measures of academic achievement and attainment. Purpose/Objective/Research Question/Focus of Study This article examines how language policy in the United States has shaped educational opportunities and outcomes for the nation's immigrant students. First, we examine the role of federal policy in shaping these students’ educational opportunities, showing how the changing political landscape in Washington has resulted in inconsistencies in funding and direction for states attempting to serve EL students. Then we focus on how two states with high concentrations of ELs— California and Texas—have responded to the needs of ELs, including the provision of bilingual education, the training and support of properly prepared teachers, and the assessments used to gauge their educational performance. Research Design The article uses secondary data sources. It draws on secondary data analysis to examine the growth of the immigrant and linguistic minority populations and their educational achievement; it draws on both historical analysis and secondary data analysis to review shifting federal policies; and it draws on demographic, achievement, and reclassification data in analyzing the education of ELs in California and Texas. Findings/Results We found that the changing political landscape in Washington has resulted in inconsistencies in funding and direction for states attempting to serve EL students. We also found that California and Texas appear to have different success rates with their EL students, with Texas reclassifying its ELs to fluent English status at higher rates and outperforming California with respect to National Assessment of Educational Progress scores for this same population. Conclusions/Recommendations The article concludes with the major recommendation that the federal government would do well to spearhead and fund a research agenda that addresses the truly important, and unanswered, questions around the education of ELs so that greater guidance can be given to the states in determining how to raise achievement and enhance the psychosocial development of these students.
Using a Bayesian approach to estimate and compare new Keynesian DSGE models for the Brazilian economy: the role for endogenous persistence

New Keynesian dynamic stochastic general equilibrium (DSGE) models have been developed for monetary policy analysis in open economies. For this purpose, the basic model must be enriched with the sources of nominal and real rigidities which are capable of explaining the observed output and inflation persistence. Under this perspective, we use the Bayesian approach to estimate and compare alternative model specifications for the Brazilian economy with respect to two endogenous persistence mechanisms widely supported by the international empirical literature: habit formation and price indexation. Using data for the inflation target period, we conclude for the relevance of both mechanisms, although the evidence is unexpectly less robust for price indexation. Furthermore, impulse-response functions are built to describe the dynamic effects of domestic and foreign real and monetary shocks.
Molecular insights into the historic demography of bowhead whales: understanding the evolutionary basis of contemporary management practices

Patterns of genetic variation observed within species reflect evolutionary histories that include signatures of past demography. Understanding the demographic component of species' history is fundamental to informed management because changes in effective population size affect response to environmental change and evolvability, the strength of genetic drift, and maintenance of genetic variability. Species experiencing anthropogenic population reductions provide valuable case studies for understanding the genetic response to demographic change because historic changes in the census size are often well documented. A classic example is the bowhead whale, Balaena mysticetus, which experienced dramatic population depletion due to commercial whaling in the late 19th and early 20th centuries. Consequently, we analyzed a large multi-marker dataset of bowhead whales using a variety of analytical methods, including extended Bayesian skyline analysis and approximate Bayesian computation, to characterize genetic signatures of both ancient and contemporary demographic histories. No genetic signature of recent population depletion was recovered through any analysis incorporating realistic mutation assumptions, probably due to the combined influences of long generation time, short bottleneck duration, and the magnitude of population depletion. In contrast, a robust signal of population expansion was detected around 70,000 years ago, followed by a population decline around 15,000 years ago. The timing of these events coincides to a historic glacial period and the onset of warming at the end of the last glacial maximum, respectively. By implication, climate driven long-term variation in Arctic Ocean productivity, rather than recent anthropogenic disturbance, appears to have been the primary driver of historic bowhead whale demography.
Supplemental Data S 1 The SRA Methyl-Cytosine-Binding Domain Links DNA and Histone Methylation

Plant Material The wild-type control in this study was the Columbia ecotype. kyp-2 and kyp-5 were isolated in the screen described in Jackson et al. [S1], and kyp-6 is a T-DNA insertion line obtained from the SALK Institute Genomic Analysis Laboratory (SALK_041474) [S2]. The met1-3 line was described in Saze et al. [S3]. The triple drm1 drm2 cmt3 mutant was made by crossing the SALK T-DNA insertions lines (CMT3, SALK_148381; DRM1, SALK_095534; DRM2, SALK_150863). All plant material (DNA for bisulfite sequencing and tissue for ChIPs) was isolated from the first-generation homozygous plants for both the met1-3 line and the drm1 drm2 cmt3 triple mutant.
Association of 3-Dimensional Cartilage and Bone Structure with Articular Cartilage Properties in and Adjacent to Autologous Osteochondral Grafts after 6 and 12 Months in a Goat Model

Objective: The articular cartilage of autologous osteochondral grafts is typically different in structure and function from local host cartilage and thereby presents a remodeling challenge. The hypothesis of this study was that properties of the articular cartilage of trochlear autografts and adjacent femoral condyle are associated with the 3-dimensional (3-D) geometrical match between grafted and contralateral joints at 6 and 12 months after surgery. Design: Autografts were transferred unilaterally from the lateral trochlea (LT) to the medial femoral condyle (MFC) in adult Spanish goats. Operated and contralateral nonoperated joints were harvested at 6 and 12 months and analyzed by indentation testing, micro–computed tomography, and histology to compare 1) histological indices of repair, 2) 3-D structure (articular surface deviation, bone-cartilage interface deviation, cartilage thickness), 3) indentation stiffness, and 4) correlations between stiffness and 3-D structure. Results: Cartilage deterioration was present in grafts at 6 months and more severe at 12 months. Cartilage thickness and normalized stiffness of the operated MFC were lower than the nonoperated MFC within the graft and proximal adjacent host regions. Operated MFC articular surfaces were recessed relative to the nonoperated MFC and exhibited lower cartilage stiffness with increasing recession. Sites with large bone-cartilage interface deviations, both proud and recessed, were associated with recessed articular surfaces and low cartilage stiffness. Conclusion: The effectiveness of cartilage repair by osteochondral grafting is associated with the match of 3-D cartilage and bone geometry to the native osteochondral structure.