Miracle-dz/UniFAR-FTUs huggingface dataset:
RoxB Is a Novel Type of Rubber Oxygenase That Combines Properties of Rubber Oxygenase RoxA and Latex Clearing Protein (Lcp)

ABSTRACT Only two types of rubber oxygenases, rubber oxygenase (RoxA) and latex clearing protein (Lcp), have been described so far. RoxA proteins (RoxAs) are c-type cytochromes of ≈70 kDa produced by Gram-negative rubber-degrading bacteria, and they cleave polyisoprene into 12-oxo-4,8-dimethyltrideca-4,8-diene-1-al (ODTD), a C15 oligo-isoprenoid, as the major end product. Lcps are common among Gram-positive rubber degraders and do not share amino acid sequence similarities with RoxAs. Furthermore, Lcps have much smaller molecular masses (≈40 kDa), are b-type cytochromes, and cleave polyisoprene to a mixture of C20, C25, C30, and higher oligo-isoprenoids as end products. In this article, we purified a new type of rubber oxygenase, RoxBXsp (RoxB of Xanthomonas sp. strain 35Y). RoxBXsp is distantly related to RoxAs and resembles RoxAs with respect to molecular mass (70.3 kDa for mature protein) and cofactor content (2 c-type hemes). However, RoxBXsp differs from all currently known RoxAs in having a distinctive product spectrum of C20, C25, C30, and higher oligo-isoprenoids that has been observed only for Lcps so far. Purified RoxBXsp revealed the highest specific activity of 4.5 U/mg (at 23°C) of all currently known rubber oxygenases and exerts a synergistic effect on the efficiency of polyisoprene cleavage by RoxAXsp. RoxB homologs were identified in several other Gram-negative rubber-degrading species, pointing to a prominent function of RoxB for the biodegradation of rubber in Gram-negative bacteria. IMPORTANCE The enzymatic cleavage of rubber (polyisoprene) is of high environmental importance given that enormous amounts of rubber waste materials are permanently released (e.g., by abrasion of tires). Research from the last decade has discovered rubber oxygenase A, RoxA, and latex clearing protein (Lcp) as being responsible for the primary enzymatic attack on the hydrophobic and water-insoluble biopolymer poly(cis-1,4-isoprene) in Gram-negative and Gram-positive rubber-degrading bacteria, respectively. Here, we provide evidence that a third type of rubber oxygenase is present in Gram-negative rubber-degrading species. Due to its characteristics, we suggest the designation RoxB for the new type of rubber oxygenase. Bioinformatic analysis of genome sequences indicates the presence of roxB homologs in other Gram-negative rubber degraders.
Varicella vaccination - the global experience

ABSTRACT Introduction: Varicella, although a frequently benign childhood disease, nevertheless represents a considerable health burden. WHO recommends including varicella vaccines in universal routine vaccination programs, and maintaining coverage >80%. Many countries have successfully introduced varicella vaccination and have benefited from lower disease burden, but many others have not adopted the vaccine. Reasons include cost commitment for a ‘mild childhood disease’ or concerns that vaccination will shift varicella to older age groups or increase herpes zoster incidence. Areas covered: This literature review summarizes the effectiveness and epidemiological impact of varicella immunization programs. Expert commentary: Varicella vaccines are immunogenic with acceptable safety profiles. One and two dose schedules are highly effective against varicella and large reductions in disease incidence, particularly moderate-severe disease, have been widely reported. There is currently no evidence to suggest that the introduction of varicella vaccination results in a shift of varicella disease burden to older age groups. Although epidemiological studies have shown an increased incidence of herpes zoster since the vaccines were launched, there are many other contributing factors, and indeed, this secular trend was evident before their introduction. In conclusion, varicella vaccination easily fits into existing immunization programs and significantly reduces the often underestimated burden of varicella.
Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Purpose: The FLT3 cell-surface receptor tyrosine kinase (CD135) is expressed in a majority of both acute lymphoid leukemia (ALL) and myeloid leukemia (AML). However, the prognostic significance of CD135 expression in AML remains unclear. We therefore evaluated the association between FLT3 surface expression and disease characteristics and outcomes in pediatric patients with AML. Experimental Design: We analyzed FLT3 receptor expression on AML blasts by multi-dimensional flow cytometry and its association with disease characteristics, clinical outcomes, and FLT3 transcript level in 367 children with AML treated on the Children's Oncology Group trial AAML0531. Results: There was high variability in blast CD135 cell-surface expression across specimens. CD135 expression measured by flow cytometry was not correlated with FLT3 transcript expression determined by quantitative RT-PCR. Overall, CD135 expression was not significantly different for patients with FLT3/WT, FLT3/ITD, or FLT3/ALM (P = 0.25). High cell-surface CD135 expression was associated with FAB M5 subtype (P < 0.001), KMT2A rearrangements (P = 0.009), and inversely associated with inv(16)/t(16;16) (P < 0.001). Complete remission rate, overall survival, disease-free survival, and relapse rates were not significantly different between patients with low and high CD135 expression. Conclusions: FLT3 cell-surface expression did not vary by FLT3 mutational status, but high FLT3 expression was strongly associated with KMT2A rearrangements. Our study found that there was no prognostic significance of FLT3 cell surface expression in pediatric AML. Clin Cancer Res; 23(14); 3649–56. ©2017 AACR.
The Escherichia coli rhaSR-PrhaBAD Inducible Promoter System Allows Tightly Controlled Gene Expression over a Wide Range in Pseudomonas aeruginosa

ABSTRACT The araC-ParaBAD inducible promoter system is tightly controlled and allows gene expression to be modulated over a wide range in Escherichia coli, which has led to its widespread use in other bacteria. Although anecdotal evidence suggests that araC-ParaBAD is leaky in Pseudomonas aeruginosa, neither a thorough analysis of this inducible promoter system in P. aeruginosa nor a concerted effort to identify alternatives with improved functionality has been reported. Here, we evaluated the functionality of the araC-ParaBAD system in P. aeruginosa. Using transcriptional fusions to a lacZ reporter gene, we determined that the noninduced expression from araC-ParaBAD is high and cannot be reduced by carbon catabolite repression as it can in E. coli. Modulating translational initiation by altering ribosome-binding site strength reduced the noninduced activity but also decreased the maximal induced activity and narrowed the induction range. Integrating the inducible promoter system into the posttranscriptional regulatory network that controls catabolite repression in P. aeruginosa significantly decreased the noninduced activity and increased the induction range. In addition to these improvements in the functionality of the araC-ParaBAD system, we found that the lacI q-Ptac and rhaSR-PrhaBAD inducible promoter systems had significantly lower noninduced expression and were inducible over a broader range than araC-ParaBAD. We demonstrated that noninduced expression from the araC-ParaBAD system supported the function of genes involved in antibiotic resistance and tryptophan biosynthesis in P. aeruginosa, problems that were avoided with rhaSR-PrhaBAD. rhaSR-PrhaBAD is tightly controlled, allows gene expression over a wide range, and represents a significant improvement over araC-ParaBAD in P. aeruginosa. IMPORTANCE We report the shortcomings of the commonly used Escherichia coli araC-ParaBAD inducible promoter system in Pseudomonas aeruginosa, successfully reengineered it to improve its functionality, and show that the E. coli rhaSR-PrhaBAD system is tightly controlled and allows inducible gene expression over a wide range in P. aeruginosa.
Preclinical Development of a Nontoxic Oral Formulation of Monoethanolamine, a Lipid Precursor, for Prostate Cancer Treatment

Purpose: Most currently available chemotherapeutic agents target rampant cell division in cancer cells, thereby affecting rapidly dividing normal cells resulting in toxic side-effects. This nonspecificity necessitates identification of novel cellular pathways that are reprogrammed selectively in cancer cells and can be exploited to develop pharmacologically superior and less toxic therapeutics. Despite growing awareness on dysregulation of lipid metabolism in cancer cells, targeting lipid biosynthesis is still largely uncharted territory. Herein, we report development of a novel nontoxic orally deliverable anticancer formulation of monoethanolamine (Etn) for prostate cancer by targeting the Kennedy pathway of phosphatidylethanolamine (PE) lipid biosynthesis. Experimental Design: We first evaluated gastrointestinal tract stability, drug–drug interaction liability, pharmacokinetic, and toxicokinetic properties of Etn to evaluate its suitability as a nontoxic orally deliverable agent. We next performed in vitro and in vivo experiments to investigate efficacy and mechanism of action. Results: Our data demonstrate that Etn exhibits excellent bioavailability, gastrointestinal tract stability, and no drug–drug interaction liability. Remarkably, orally fed Etn inhibited tumor growth in four weeks by approximately 67% in mice bearing human prostate cancer PC-3 xenografts without any apparent toxicity. Mechanistically, Etn exploits selective overexpression of choline kinase in cancer cells, resulting in accumulation of phosphoethanolamine (PhosE), accompanied by downregulation of HIF-1α that induces metabolic stress culminating into cell death. Conclusions: Our study provides first evidence for the superior anticancer activity of Etn, a simple lipid precursor formulation, whose nontoxicity conforms to FDA-approved standards, compelling its clinical development for prostate cancer management. Clin Cancer Res; 23(14); 3781–93. ©2017 AACR.
Pre-eclampsia and risk of subsequent hypertension: in an American Indian population

ABSTRACT Background and Objectives: Pre-eclampsia (PE) shares a number of proposed pathophysiologic mechanisms related to those implicated in cardiovascular disease (CVD), such as endothelial dysfunction, inflammation, insulin resistance, and impaired renal regulation. PE has also been associated with subsequent hypertension, CVD, and related mortality in later life. Methods: At follow-up, the four most recent blood pressures, body mass index (BMI), and use of hypertensive medications were recorded from clinic visits of 130 PE cases and 289 normal pregnancies. Student’s t test, Chi-square testing, multivariate linear, and logistic regression were used in analysis. Results: Follow-up measurements occurred a mean of 13.11 years post PE pregnancy. Multivariate linear regression showed a significant and independent association between current systolic blood pressure and previous history of PE (β = 4.47, p = 0.04), while adjusting for age, BMI, and blood pressure from 1 year prior to and up to the 20th week of gestation. A similarly adjusted multivariate logistic regression model found an odds ratio of 3.43, 95% CI 1.83–6.43, p = 0.001 for subsequent hypertension. Logistic regression analysis of the quartile with follow-up of less than 7.19 years also shows independent association of prior PE with subsequent hypertension. Discussion and Conclusions: PE appears to confer risk of subsequent hypertension on this cohort of American Indian women within as little as 8 years. This risk is independent of additional risk factors such as increased age, BMI, and blood pressure prior to 20 weeks of gestation. There is evidence of increased risk among those with more severe PE.
EXPERIMENTAL INVESTIGATIONS ON THE PREMIXED FLAMES STABILIZED ON WIRE MESH MATERIALS

Experiments were performed to identify the combustion characteristics of the premixed flames stabilized on the Inconel and Kanthal wire woven mesh materials. NOx emissions linearly increased at lower firing rates, followed by a rapid increase at higher firing rates. At the lower firing rates, the prompt NOx mechanism was the major route, and the thermal NOx formation became dominant at the higher firing rates due to an increase in gas temperatures. The CO concentrations generally decreased to reach the minimum and increased again with firing rates. The wire surface temperatures rapidly increased at lower firing rates, suggesting that the heat generated from the combustion process was effectively dissipated from the materials by radiation. The gradual, linear increase in the surface temperatures at higher firing rates supported that the flame was detached from the materials due to excessive heat from combustion. These behaviors of the flame were thought to be responsible for the trends of the CO and NOx formations. The pressure drop in the material was dominated by the mesh size, which determined the velocity of unburned mixture, rather than the material properties. The coefficients of the Forchheimer equation were deduced from the measured pressure drop. The Inconel 24×24 and 26×26 meshes showed the best performance in the materials tested, in terms of the NOx and CO emissions and pressure drop.Copyright © 2008 by ASME
Anticipatory Eye Movements While Watching Continuous Action Across Shots in Video Sequences: A Developmental Study.

Eye movements were recorded as 12-month-olds (n = 15), 4-year-olds (n = 17), and adults (n = 19) watched a 15-min video with sequences of shots conveying continuous motion. The central question was whether, and at what age, viewers anticipate the reappearance of objects following cuts to new shots. Adults were more likely than younger viewers to make anticipatory eye movements. Four-year-olds responded to transitions more slowly and tended to fixate the center of the screen. Infants' eye movement patterns reflected a tendency to react rather than anticipate. Findings are consistent with the hypothesis that adults integrate content across shots and understand how space is represented in edited video. Results are interpreted with respect to a developing understanding of film editing due to experience and cognitive maturation.
MicroRNA-145 influences the balance of Th1/Th2 via regulating RUNX3 in asthma patients

ABSTRACT Aim of the Study: To delineate the underlying mechanism of microRNA-145 modulate the balance of Th1/Th2 via targeting RUNX3 in asthma patients. Materials and Methods: Peripheral blood samples were collected from asthma patients and healthy controls. CD4+ T cells were isolated and cultured. Using quantitative PCR detect, the level of microRNA-145 and RUNX3 mRNA level in the CD4+ T cells from asthma patients and healthy controls, meanwhile, western blot was used to detect the RUNX3 protein level. Th1 or Th2 related cytokines were measured by enzyme-linked immunosorbent assay. Dual-Luciferase Reporter Assay was performed to confirm the correlation between microRNA-145 and RUNX3. MicroRNA-145 mimic or inhibitor was transfected in the CD4+ T cells and the changes of RUNX3 level, Th1 or Th2 related cytokines and the percentage of Th1 and Th2 were observed after transfection. Results: MicroRNA-145 level of CD4+ T cells was higher with a lower RUNX3 expression in asthma patients. There is negative correlation between microRNA-145 and RUNX3. Th2 hyperactivity and Th1 deficiency was detected in the CD4+ T cells of asthma patients. Dual-Luciferase Reporter Assay has shown that RUNX3 is a target of microRNA. Up-regulation or down-regulation of miR-145 level caused RUNX3 expression changes in CD4+ T cells and influence the related cytokines. Inhibition of microRNA-145 may reverse the imbalance of Th1/Th2 in asthma patients. Conclusion: MicroRNA-145 could regulate the balance of Th1/Th2 through targeting the RUNX3 in asthma patients. MicroRNA-145 and RUNX3 may be used as biomarkers or targets in the diagnosis or therapy of asthma.
Dissipative control for state-saturated discrete time-varying systems with randomly occurring nonlinearities and missing measurements

In this paper, the dissipative control problem is investigated for a class of discrete time-varying systems with simultaneous presence of state saturations, randomly occurring nonlinearities as well as multiple missing measurements. In order to render more practical significance of the system model, some Bernoulli distributed white sequences with known conditional probabilities are adopted to describe the phenomena of the randomly occurring nonlinearities and the multiple missing measurements. The purpose of the addressed problem is to design a time-varying output-feedback controller such that the dissipativity performance index is guaranteed over a given finite-horizon. By introducing a free matrix with its infinity norm less than or equal to 1, the system state is bounded by a convex hull so that some sufficient conditions can be obtained in the form of recursive nonlinear matrix inequalities. A novel controller design algorithm is then developed to deal with the recursive nonlinear matrix inequalities. Furthermore, the obtained results are extended to the case when the state saturation is partial. Two numerical simulation examples are provided to demonstrate the effectiveness and applicability of the proposed controller design approach.
Synthesis, Characterization and Biological Activities of New Symmetric Bis-1,2,3-Triazoles with Click Chemistry.

BACKGROUND 1,2,3-Triazole and its derivatives have important biological activities such as antimicrobial, anti-allergic, analgesic, anti-HIV, antiinflammatory, anticancer, antimalarial and antituberculosis. Other significant triazole derivatives are 1,2,4-triazoles which play a very important role in the medicinal chemistry due to the antiinflammatory, antimicrobial, antimigraine, anticancer, antimicrobial and antimycotic activities. In this study, we aimed to synthesize a new series of bis-1,2,3-triazole derivatives including 1,2,4-triazole to obtain more effective biological activities. METHODS In this study, a new series of bis-1,2,3-triazole compounds (9,10,11) were synthesized. Antimicrobial Activity: Disc diffusion method was used. Enzyme Inhibition: α-Glucosidase Inhibition was investigated. Antioxidant Activities: DPPH Radical Scavenging, Phosphomolybdenum- Reducing Antioxidant Power (PRAP) and Ferrous Ion-Chelating methods were used. RESULTS Compounds 9a, 9c, 9e, 9f, 10a, 10b, 10d, 11a, 11b and 11f showed significant antibacterial and antifungal activity against all the strains tested. Compound 9g exhibited the highest AChE inhibition. Compounds 10f, 11a and 11g showed remarkable activity against the BuChE enzyme. Compound 10f has the highest antioxidant activities. CONCLUSION The compounds 9a, 9c, 9e, 9f, 10a, 10b, 10d, 11a, 11b and 11f exhibit the best antimicrobial activity against the bacteria and fungi C.albicans, Y. enterocolitica, E. coli, Candida albicans, Yersinia enterocolitica. Compound 9g exhibit the highest AChE inhibition with 72.67 ± 3.92% at 100 µg/mL. Compounds 10f, 11a and 11g showed remarkable activity against the BuChE enzyme compared to galantamine. Many of the compounds exhibited significant α-glucosidase inhibition activities. Compound 10f has the highest antioxidant activities (DPPH, PRAP, ferrous ionchelating) with 27.71 ± 0.85%, 0.689 ± 0.005, 42.07 ± 2.48 at 100 µg/mL, respectively.
Single-Epoch Supernova Classification with Deep Convolutional Neural Networks

Supernovae Type-Ia (SNeIa) play a significant role in exploring the history of the expansion of the Universe, since they are the best-known standard candles with which we can accurately measure the distance to the objects. Finding large samples of SNeIa and investigating their detailed characteristics have become an important issue in cosmology and astronomy. The current photometric supernova surveys produce vastly more candidates than can be followed up spectroscopically, highlighting the need for effective classification methods. Existing methods relied on a photometric approach that first measures the luminance of supernova candidates precisely and then fits the results to a parametric function of temporal changes in luminance. However, it inevitably requires multi-epoch observations and complex luminance measurements. In this work, we present a novel method for classifying SNeIa simply from single-epoch observation images without any complex measurements, by effectively integrating the state-of-the-art computer vision methodology into the standard photometric approach. Our method first builds a convolutional neural network for estimating the luminance of supernovae from telescope images, and then constructs another neural network for the classification, where the estimated luminances and observation dates are used as features for classification. Both of the neural networks are integrated into a single deep neural network to classify SNeIa directly from observation images. Experimental results show the effectiveness of the proposed method and reveal classification performance comparable to existing photometric methods with multi-epoch observations.
Cognitive Impairment, Alzheimer’s Disease, and Other Dementias in the Lives of Lesbian, Gay, Bisexual and Transgender (LGBT) Older Adults and Their Caregivers: Needs and Competencies

Cognitive impairment, Alzheimer’s disease, and other dementias are important health concerns for older adults. As a marginalized and growing segment of the older adult population, lesbian, gay, bisexual, and transgender (LGBT) older adults face distinct risk factors related to cognitive impairment and dementias, including social isolation, discrimination, barriers to health care access, limited availability of and support for caregivers, and higher rates of certain chronic illnesses. We examine cognitive impairment and dementias among LGBT older adults, describe their unique risk factors, and outline key competencies for health care and human service providers to ensure culturally relevant care for LGBT older adults experiencing cognitive impairment, Alzheimer’s disease, or other dementias, as well as their caregivers, families, and communities. Implications include developing an awareness of the context of LGBT older adults’ lives and relationships, the importance of early detection and support, and the development of policies and practices that promote community-level advocacy and education.
Different Clinical Presentations of the Same Epidemic Keratoconjunctivitis Outbreak in Premature Babies and Their Parents

ABSTRACT Purpose: This study aims to report the differences in the findings of epidemic keratoconjunctivitis (EKC) between premature babies and their families at an outbreak of viral conjunctivitis. Methods: In this prospective observational study, premature babies (25 patients) who were diagnosed with EKC and the family members (30 patients, mother, father, or grandmother/father) who had EKC after contacting them were monitored closely. Patients were divided into two groups as preterm babies (group 1) and adults (group 2). Results: The present study investigated particularly subepithelial corneal infiltrates (SEI) occurrence after EKC, which was searched for at each visit in the 2nd week, 1st month, and 3rd month after EKC. Distribution of SEI in two groups was statistically significant at each visit (<0.0001). There was more SEI in group 2. Conclusions: None of the preterm cases were found to have SEI after EKC.