Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms of protection of cationic lipid-DNA complexes during lyophilization.

Gene therapy using nonviral vectors offers advantages over viral methods. However, the instability of aqueous suspensions of cationic lipid-DNA complexes is a major problem that must be overcome to develop this therapeutic modality on a pharmaceutical scale. Disaccharides have been reported to protect lipid-DNA complexes during lyophilization, and recovery of transfection correlates with the retention of particle size. However, the mechanism by which disaccharides achieve this protection is not known. The purpose of this study was to investigate the protective mechanism by lyophilizing cationic lipid-DNA complexes with a variety of solutes that have different physical behaviors during the lyophilization process. In agreement with previous studies, disaccharides conferred protection to lipid-DNA complexes. By contrast, a large polymeric sugar, hydroxyethyl starch, did not protect as well. The level of protection by additives, such as mannitol, that crystallized during lyophilization was also less than that of the disaccharides, but some protection was nonetheless observed. These data suggest that water replacement plays a significant role in protecting complexes during lyophilization. A second mechanism that prevents aggregation by diluting complexes within freeze-concentrated solutions or dried cakes may also contribute to protection. Sample vitrification did not correlate with maintenance of transfection efficiency. Elucidation of the mechanism(s) by which cationic lipid-DNA complexes are protected during lyophilization will permit a rational approach to the development of stable, lyophilized formulations.
Enterprise to Computer: Star Trek chatbot

Human interactions and human-computer interactions are strongly influenced by style as well as content. Adding a persona to a chatbot makes it more human-like and contributes to a better and more engaging user experience. In this work, we propose a design for a chatbot that captures the "style" of Star Trek by incorporating references from the show along with peculiar tones of the fictional characters therein. Our Enterprise to Computer bot (E2Cbot) treats Star Trek dialog style and general dialog style differently, using two recurrent neural network Encoder-Decoder models. The Star Trek dialog style uses sequence to sequence (SEQ2SEQ) models (Sutskever et al., 2014; Bahdanau et al., 2014) trained on Star Trek dialogs. The general dialog style uses Word Graph to shift the response of the SEQ2SEQ model into the Star Trek domain. We evaluate the bot both in terms of perplexity and word overlap with Star Trek vocabulary and subjectively using human evaluators.
Syndromic Diagnosis of Malaria in Rural Sierra Leone and Proposed Additions to the National Integrated Management of Childhood Illness Guidelines for Fever

Many countries in Africa, including Sierra Leone, have adopted artemisinin-based combination therapy as first-line therapy for treatment of patients with malaria. Because laboratory testing is often unavailable in rural areas, the cost-benefit and viability of this approach may depend on accurately diagnosing malaria by using clinical criteria. We assessed the accuracy of syndromic diagnosis for malaria in three peripheral health units in rural Sierra Leone and determined factors that were associated with an accurate malaria diagnosis. Of 175 children diagnosed with malaria on syndromic grounds, 143 (82%) were confirmed by the Paracheck-Pf test. In a multivariate analysis, splenomegaly (P = 0.04) was the only clinical sign significantly associated with laboratory-confirmed malaria, and sleeping under a bed net was protective (P = 0.05). Our findings show that clinical malaria is diagnosed relatively accurately in rural Sierra Leone. Incorporating bed net use and splenomegaly into the national Integrated Management of Childhood Illness guidelines for evaluation of fever may further enhance diagnostic accuracy for malaria.
Lineage Specific Methylation of the Elf5 Promoter in Mammary Epithelial Cells

Recent characterization of mammary stem and progenitor cells has improved our understanding of the transcriptional network that coordinates mammary development; however, little is known about the mechanisms that enforce lineage commitment and prevent transdifferentiation in the mammary gland. The E‐twenty six transcription factor Elf5 forces the differentiation of mammary luminal progenitor cells to establish the milk producing alveolar lineage. Methylation of the Elf5 promoter has been proposed to act as a lineage gatekeeper during embryonic development. We used bisulphite sequencing to investigate in detail whether Elf5 promoter methylation plays a role in lineage commitment during mammary development. An increase in Elf5 expression was associated with decreasing Elf5 promoter methylation in differentiating HC11 mammary cells. Similarly, purified mammary epithelial cells from mice had increased Elf5 expression and decreased promoter methylation during pregnancy. Finally, analysis of epithelial subpopulations revealed that the Elf5 promoter is methylated and silenced in the basal, stem cell‐containing population relative to luminal cells. These results demonstrate that Elf5 promoter methylation is lineage‐specific and developmentally regulated in the mammary gland in vivo, and suggest that loss of Elf5 methylation specifies the mammary luminal lineage, while continued Elf5 methylation maintains the stem cell and myoepithelial lineages. STEM CELLS 2011;29:1611–1619
16S rDNA-based metagenomic analysis of dental plaque and lung bacteria in patients with severe acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are leading causes of mortality in hospital intensive care units. We sought to determine whether dental plaque biofilms might harbor pathogenic bacteria that can eventually cause lung infections in patients with severe AE-COPD. MATERIAL AND METHODS Paired samples of subgingival plaque biofilm and tracheal aspirate were collected from 53 patients with severe AE-COPD. Total bacterial DNA was extracted from each sample individually for polymerase chain reaction amplification and/or generation of bacterial 16S rDNA sequences and cDNA libraries. We used a metagenomic approach, based on bacterial 16S rDNA sequences, to compare the distribution of species present in dental plaque and lung. RESULTS Analysis of 1060 sequences (20 clones per patient) revealed a wide range of aerobic, anaerobic, pathogenic, opportunistic, novel and uncultivable bacterial species. Species indistinguishable between the paired subgingival plaque and tracheal aspirate samples (97-100% similarity in 16S rDNA sequence) were dental plaque pathogens (Aggregatibacter actinomycetemcomitans, Capnocytophaga sputigena, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) and lung pathogens (Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Streptococcus pneumoniae). Real-time polymerase chain reaction of 16S rDNA indicated lower levels of Pseudomonas aeruginosa and Porphyromonas gingivalis colonizing the dental plaques compared with the paired tracheal aspirate samples. CONCLUSION These results support the hypothesis that dental bacteria may contribute to the pathology of severe AE-COPD.
Disturbances in beta-cell function in impaired fasting glycemia.

In a cross-sectional study, we assessed beta-cell function and insulin sensitivity index (ISI) with hyperglycemic clamps (10 mmol/l) in 24 subjects with impaired fasting glycemia (IFG, fasting plasma glucose [FPG] between 6.1 and 7.0 mmol/l), 15 type 2 diabetic subjects (FPG >7.0 mmol/l), and 280 subjects with normal fasting glycemia (NFG, FPG <6.1 mmol/l). First-phase insulin release (0-10 min) was lower in IFG (geometric mean 541 pmol/l.10 min; 95% confidence interval [CI] 416-702 pmol/l.10 min) and in type 2 diabetes (geometric mean 376 pmol/l.10 min; 95% CI 247-572 pmol/l.10 min) than NFG (geometric mean 814 pmol/l.10 min; 95% CI 759-873 pmol/l.10 min) (P < 0.001). Second-phase insulin secretion (140-180 min) was also lower in IFG (geometric mean 251 pmol/l; 95% CI 198-318 pmol/l; P = 0.026) and type 2 diabetes (geometric mean 157 pmol/l; 95% CI 105-235 pmol/l; P < 0.001) than NFG (geometric mean 295 pmol/l; 95% CI 276-315 pmol/l). IFG and type 2 diabetic subjects had a lower ISI (0.15 plus minus 0.02 and 0.16 plus minus 0.02 micromol/kg fat-free mass [FFM]/min/pmol/l, respectively) than NFG (0.24 plus minus 0.01 micromol/kg FFM/min/pmol/l, P < 0.05). We found a stepwise decline in first-phase (and second-phase) secretion in NFG subjects with progressive decline in oral glucose tolerance (P < 0.05). IFG subjects with impaired glucose tolerance (IGT) had lower first-phase secretion than NFG subjects with IGT (P < 0.02), with comparable second-phase secretion and ISI. NFG and IFG subjects with a diabetic glucose tolerance (2-h glucose >11.1 mmol/l) had a lower ISI than their respective IGT counterparts (P < 0.05). We conclude that the early stages of glucose intolerance are associated with disturbances in beta-cell function, while insulin resistance is seen more markedly in later stages.
Effects of pH on uranium uptake and oxidative stress responses induced in Arabidopsis thaliana

Uranium (U) causes oxidative stress in Arabidopsis thaliana plants grown at pH 5.5. However, U speciation and its toxicity strongly depend on environmental parameters, for example pH. It is unknown how different U species determine U uptake and translocation within plants and how they might affect the oxidative defense mechanisms of these plants. The present study analyzed U uptake and oxidative stress‐related responses in A. thaliana (Columbia ecotype) under contrasted U chemical speciation conditions. The 18‐d‐old seedlings were exposed for 3 d to 25 µM U in a nutrient solution of which the pH was adjusted to 4.5, 5.5, 6.5, or 7.5. Results indicate that there is a different rate of U uptake and translocation at the different pHs, with high uptake and low translocation at low pH and lower uptake but higher translocation at high pH. After U exposure, an increased glutathione reductase activity and total glutathione concentration were observed in U‐exposed roots, pointing toward an important role for glutathione in the root defense system against U either by chelation or by antioxidative defense mechanisms. In leaves, antioxidative defense mechanisms were activated on U exposure, indicated by increased superoxide dismutase and catalase activity. As it seems that U toxicity is influenced by pH, it is important to consider site‐specific characteristics when making U risk assessments. Environ Toxicol Chem 2013;32:2125–2133. © 2013 SETAC
The quality changes in fresh frozen plasma of the blood donors at high altitude

Objective According to the international guidelines, fresh frozen plasma (FFP) is unanimously used to treat coagulation disorders. The quality of FFP is critical for the clinical transfusion. Till now, few studies have integratedly evaluated the differences of FFP from blood donors at between high altitude (HA) and low altitude (LA). Besides, there were no special quality standards for HA FFP in China. Materials and methods Up to 41 HA (Lhasa, 3700 m) and 46 LA (Chengdu, 500 m) blood donors were included in our study to estimate the differences of FFP from HA and LA blood donors. The concentration of total plasma proteins, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen (Fbg), factor (F) II, FV, FVII, FVIII, FIX, FX, FXI, FXII, D-dimer, protein C (PC), protein S (PS), antithrombin III (ATIII) and von Willebrand factor antigen (vWF:Ag) were determined, respectively. Results As compared with FFP of LA blood donors, the total protein content of HA blood donors showed a significant decrease (65.2±8.9 vs.57.2±6.3 g/L; p<0.001); PT, aPTT, TT were significantly increased (p<0.001); the levels of FII, FV, FVII, FVIII, FIX, FX, FXI, FXII and vWF:Ag were notably decreased (all p<0.05), whereas Fbg and D-dimer were dramaticly increased (p = 0.038). Additionly, in HA blood donors, vWF: Ag and FVIII:C of O-group was significantly lower (p<0.05) than that of non-O-group. It should be noted that FVIII:C of HA blood donors (0.64±0.10 IU/mL) was lower than the current Chinese quality requirements for FFP (≥ 0.7 IU/ml). No significant differences were observed in PC, PS and ATIII. Conclusion In general, our findings showed that the quality of FFP was significantly different between HA and LA blood donors, and the current Chinese quality requirements of FFP are not suitable for HA FFP. Therefore, setting up a special quality requirement for HA is quite necessary and meaningful.
Good accuracy of ultrasound estimations of fetal weight performed by midwives

Background. This study was undertaken to evaluate the quality of ultrasound estimation of fetal weight when performed by midwives experienced in ultrasound examinations. We also examined whether the accuracy was affected by fetal presentation, twin pregnancy or birth weight category. The results of 5 different formulas were compared to determine which was most accurate in our study population. Methods. The study population consisted of 620 fetuses in 607 pregnancies, on whom fetal weight estimations had been performed within 3 days prior to delivery. The group of twins (n = 27) was analysed separately. Results achieved by Hadlock 2 formula used in our unit were compared with 4 other widely used formulas for estimation of fetal weight. Results. With Hadlock 2 formula, mean absolute percent error was 6.2% and SD of error was 7.6% of mean birth weight. A total of 81% of estimates were within 10% of the actual birth weight. All the formulas tended to overestimate the weight of twins and fetuses weighing <2,500 g, and underestimate the weight of fetuses >4,000 g. Presentation of the fetus did not significantly influence the accuracy. The formula Hadlock 2, using 3 parameters (biparietal diameter, abdominal circumference and femur length) gave the highest ICC of 0.910. Conclusions. Ultrasound estimation of fetal weight performed by midwives is feasible and of similar accuracy as in the original studies. Major errors may occur both in small and large birth weight groups.
Propolis Improves Periodontal Status and Glycemic Control in Patients With Type 2 Diabetes Mellitus and Chronic Periodontitis: A Randomized Clinical Trial.

BACKGROUND Propolis is a natural resin made by bees from various plant sources and exerts antimicrobial, anti-inflammatory, immunomodulatory, antioxidant, and antidiabetic properties. The purpose of this study is to assess adjunctive benefit of propolis supplementation in individuals with chronic periodontitis (CP) and type 2 diabetes mellitus (DMt2) receiving scaling and root planing (SRP). METHODS A 6-month masked, randomized clinical trial comparing SRP with placebo (placebo + SRP group, n = 26) or SRP combined with a 6-month regimen of 400 mg oral propolis once daily (propolis + SRP group, n = 24) was performed in patients with long-standing DMt2 and CP. Treatment outcomes included changes in hemoglobin (Hb) A1c (primary outcome), fasting plasma glucose (FPG), serum N€-(carboxymethyl) lysine (CML), and periodontal parameters (secondary outcomes). RESULTS After 3 and 6 months, average HbA1c levels in the propolis group decreased significantly by 0.82% and 0.96% units, respectively (P <0.01); however, there were no significant differences in the placebo group. Likewise, FPG and CML levels were significantly reduced in the propolis group, but not in the placebo group. After therapy, periodontal parameters of CP were significantly improved in both groups. The propolis group showed significantly greater probing depth reduction and clinical attachment level gain than the control group after 3 and 6 months. CONCLUSION A 6-month regimen of 400 mg propolis once daily is a potentially viable adjunct to SRP that significantly reduces levels of HbA1c, FPG, and CML, and improves periodontal therapy outcome in people with DMt2 and CP.
High vitamin D status in younger individuals is associated with low circulating thyrotropin.

BACKGROUND Vitamin D is an immunomodulator and may affect autoimmune thyroid diseases. Vitamin D has also been shown to influence thyrocytes directly by attenuating thyrotropin (TSH)-stimulated iodide uptake and cell growth. However, it is unclear how vitamin D status is related to TSH at the population level. The goal of the present study was to investigate the relationship between vitamin D status and TSH levels according to thyroid autoantibodies in a population-based health survey in Thailand. METHODS A total of 2582 adults, aged 15-98 years, were randomly selected according to the geographical region from the Thailand 4th National Health Examination Survey sample. By study design, the sexes were equally represented. Serum levels of 25-hydroxyvitamin D [25(OH)D], TSH, the thyroid peroxidase antibody (TPOAb), and the thyroglobulin antibody (TgAb) were measured in all subjects. RESULTS The mean age was 55.0±0.4 (SE) years. In subjects positive for serum TgAb, serum TSH levels were higher, whereas total serum 25(OH)D levels were lower. In addition, the prevalence of vitamin D insufficiency in TgAb-positive subjects was significantly higher than that observed in TPOAb- and TgAb-negative subjects, whether based on cutoff values of 20 or 30 ng/mL: 8.3% vs. 5.6%, p<0.05; or 47.6% vs. 42.0%, p<0.05, respectively. However, vitamin D status was not associated with positive TPOAb and/or TgAb after controlling for sex and age. To explore the probable interaction between vitamin D status and age on serum TSH, analyses were performed according to age tertiles; it was found that higher 25(OH)D levels were independently associated with lower TSH, but only in subjects in the lowest age tertile. CONCLUSIONS This population-based study showed that high vitamin D status in younger individuals is associated with low circulating TSH.
Hurricanes accelerated the Florida–Bahamas lionfish invasion

In this study, we demonstrate how perturbations to the Florida Current caused by hurricanes are relevant to the spread of invasive lionfish from Florida to the Bahamas. Without such perturbations, this current represents a potential barrier to the transport of planktonic lionfish eggs and larvae across the Straits of Florida. We further show that once lionfish became established in the Bahamas, hurricanes significantly hastened their spread through the island chain. We gain these insights through: (1) an analysis of the direction and velocity of simulated ocean currents during the passage of hurricanes through the Florida Straits and (2) the development of a biophysical model that incorporates the tolerances of lionfish to ocean climate, their reproductive strategy, and duration that the larvae remain viable in the water column. On the basis of this work, we identify 23 occasions between the years 1992 and 2006 in which lionfish were provided the opportunity to breach the Florida Current. We also find that hurricanes during this period increased the rate of spread of lionfish through the Bahamas by more than 45% and magnified its population by at least 15%. Beyond invasive lionfish, we suggest that extreme weather events such as hurricanes likely help to homogenize the gene pool for all Caribbean marine species susceptible to transport.
How Glucosinolates Affect Generalist Lepidopteran Larvae: Growth, Development and Glucosinolate Metabolism

Multiple lepidopteran larvae feed successfully on plants containing glucosinolates despite the diverse array of toxic and deterrent breakdown products, such as isothiocyanates (ITCs), formed upon plant damage. While much is known about how specialist lepidopterans metabolize and tolerate glucosinolates, there is little information about the metabolic fate of these plant defense compounds in specialized herbivores. Employing 13C- and 14C-labeled 4-methylsulfinylbutyl glucosinolate (glucoraphanin), we identified and quantified the major detoxification products of glucosinolates and ITCs in selected specialized and generalist larvae. While specialists prevented glucosinolate hydrolysis or diverted hydrolysis to form nitriles, hydrolysis in generalists proceeded to toxic ITCs, of which a portion were conjugated to glutathione. However, a large amount of ITCs remained unmodified, which may have led to the observed negative effects on growth and development. The performance of two generalist-feeding caterpillars, Spodoptera littoralis (African cotton leafworm) and Mamestra brassicae (cabbage moth) on Arabidopsis thaliana Col-0 and various glucosinolate-deficient mutants was investigated from hatching until pupation. We found that glucosinolates negatively affected larval growth and development, but not survival, with aliphatic glucosinolates having stronger effects than indolic glucosinolates, and the combination of the two glucosinolate types being even more detrimental to growth and development. Curiously, last instar larvae grew better on wild type than on non-glucosinolate-containing plant lines, but this could not be attributed to a change in detoxification rate or feeding behavior. Glucosinolates thus appear to be effective defenses against generalist lepidopteran herbivores at least during most stages of larval development. Nevertheless, the reversal of negative effects in the oldest instar is intriguing, and further investigation of this phenomenon may shed light on how generalists adjust their physiology to feed on diets with many different types of plant defense compounds.
α-Synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins

α-Synuclein (αS) is a 140-residue neuronal protein that forms insoluble cytoplasmic aggregates in Parkinson's disease (PD) and several other neurodegenerative disorders. Two missense mutations (A53T and A30P) are linked to rare forms of familial PD. The normal function of αS is unknown, and cultured cell systems that model its modification from soluble monomers to aggregated forms have not been reported. Through a systematic centrifugal fractionation of mesencephalic neuronal cell lines and transgenic mouse brains expressing wild-type or A53T human αS, we observed unusual, previously unrecognized species of αS that migrate well above the 17-kDa monomeric form in denaturing gels. Incubation at 65°C of high-speed cytosols from cells or brains revealed a modified αS species migrating at ≈36 kDa and an extensive higher molecular mass αS-reactive smear. Extraction of the cytosols with chloroform/methanol or with a resin (Lipidex 1000) that binds fatty acids resulted in a similar pattern of higher molecular mass αS forms. On the basis of this effect of delipidation, we reexamined the primary structure of αS and detected a motif at the N and C termini that is homologous to a fatty acid-binding protein signature. In accord, we found that purified human αS binds oleic acid, with an apparent Kd of 12.5 μM. We also observed an enhanced association of A53T αS with microsomal membranes in both mesencephalic cells and transgenic mouse brains. We conclude that αS has biochemical properties and a structural motif that suggest it is a novel member of the fatty acid-binding protein family and may thus transport fatty acids between the aqueous and membrane phospholipid compartments of the neuronal cytoplasm.