Miracle-dz/UniFAR-FTUs huggingface dataset:
Cdt1 Forms a Complex with the Minichromosome Maintenance Protein (MCM) and Activates Its Helicase Activity*

Mcm4/6/7 forms a complex possessing DNA helicase activity, suggesting that Mcm may be a central component for the replicative helicase. Although Cdt1 is known to be essential for loading of Mcm onto the chromatin, its precise role in pre-RC formation and replication initiation is unknown. Using purified proteins, we show that Cdt1 forms a complex with Mcm4/6/7, Mcm2/3/4/5/6/7, and Mcm2/4/6/7 in glycerol gradient fractionation through interaction with Mcm2 and Mcm4/6. In the glycerol gradient fractionation, Mcm4/6/7-Cdt1 forms a complex (speculated to be a (Mcm4/6/7)2-Cdt13 assembly) in the presence of ATP, which is significantly larger than the Mcm4/6/7-Cdt1 complex generated in its absence. Furthermore, DNA binding and helicase activities of Mcm4/6/7 are significantly stimulated by Cdt1 protein in vitro. We generd a Cdt1 mutant, which fails to stimulate DNA binding and helicase activities of4/6/7. This mutant Cdt1 showed reduced interaction with Mcm and is deficient in the formation of a high molecular weight complex with Mcm. Thus, a productive interaction between Cdt1 and MCM appears to be essential for efficient loading of MCM onto template DNA, as well as for the efficient unwinding reaction.
Opinion mining and sentiment analysis on online customer review

The opinion mining is very much essential in e-commerce websites, furthermore advantageous with individual. An ever increasing amount of results are stored in the web as well as the amount of people would acquiring items from web are increasing. As a result, the users' reviews or posts are increasing day by day. The reviews toward shipper sites express their feeling. Any organization for example, web forums, discourse groups, blogs etc., there will be an extensive add up for information. Records identified with items on the Web, which are functional to both makers and clients. The process of finding user opinion about the topic or product or problem is called as opinion mining. It can also be defined as the process of automatic extraction of knowledge by means of opinions expressed by the user who is currently using the product about some product is called as opinion mining. Analyzing the emotions from the extracted opinions is defined as Sentiment Analysis. The goal of opinion mining and Sentiment Analysis is to make computer able to recognize and express emotion. This work concentrates on mining reviews from the websites like Amazon, which allows user to freely write the view. It automatically extracts the reviews from the website. It also uses algorithm such as Naïve Bayes classifier, Logistic Regression and SentiWordNet algorithm to classify the review as positive and negative review. At the end we have used quality metric parameters to measure the performance of each algorithm.
Comparison of Transgastric NOTES and Laparoscopic Peritoneoscopy for Detection of Peritoneal Metastases

Background:Transgastric peritoneoscopy (TGP) may be a future alternative to the diagnostic laparoscopy (LAP). Objective:To create a model of peritoneal metastases for development of TGP and to employ this model to compare TGP to LAP. Methods:Small beads were stapled in porcine peritoneal cavities to simulate metastases. Using a noninferiority design a sample size of 64 beads was determined, which were divided over 12 animals. Randomization was performed for number and location of beads. LAP was performed by one of 2 blinded surgeons. TGP was then performed in the same pig using either standard endoscopic accessories (TGP-s) or a specially designed toolkit (TGP-t) in randomized order by 1 of 2 blinded endoscopists. Primary outcome was number of beads found and touched during peritoneoscopy. Results:Locations of beads included: abdominal peritoneum (14 beads), diaphragm (11), surface of liver and hepatoduodenal ligament (32), and miscellaneous sites (7). LAP detected 61 beads (yield = 95%), TGP-s 40 beads (63%), and TGP-t 40 beads (63%). TGP-s and TGP-t were both inferior in comparison with LAP (P = 0.8465 and P = 0.7440 respectively). TGP-s and TGP-t were similar in number, distribution and time to detect beads. TGP was superior for detecting beads on the abdominal and diaphragmatic peritoneum than for the liver, namely TGP-s: 23/25 (92%) versus 12/32 (38%) (P < 0.001); TGP-t: 25/25 (100%) versus 11/32 (34%) (P < 0.001). Conclusion:In this first prospective, blinded, comparative trial TGP was inferior to LAP for the detection of simulated metastases. Future development for NOTES peritoneoscopy should focus on improved access to the region of the liver and enhanced endoscopic optics and performance.
Long-term adherence to continuous positive airway pressure in patients with rapid eye movement-only obstructive sleep apnea: a prospective cohort study.

Background Obstructive sleep apnea (OSA) during rapid eye movement (REM) sleep is a special form of OSA that occurs predominantly during REM sleep. No study has assessed the long-term adherence to continuous positive airway pressure (CPAP) among patients with REM-only OSA. To objectively assess the long-term adherence to CPAP therapy among patients with REM-predominant (REM-only) OSA. Methods This was a prospective observational cohort study that included consecutive patients who were diagnosed with OSA. Patients were divided into the following two groups: (I) REM-only OSA [an apnea hypopnea index (AHI) of ≥5, with a REM-AHI/NREM-AHI of >2, an NREM-AHI of <15, and a minimum of 15 min of REM-sleep duration], and (II) non-stage specific OSA. Follow-up was performed at 1, 6 and 12 months after the initiation of CPAP-therapy. Results The study included 175 patients; 30 met the criteria for REM-only OSA, and the remaining patients constituted the non-stage specific OSA group. The number of hours of CPAP use per day was significantly lower in the REM-only OSA group at 1, 6 and 12 months compared to the non-stage specific OSA group. At 12 months, the number of hours used per day was 3.8±1.8 and 5.1±2.1 hours in the REM-only and non-stage specific OSA groups, respectively (P=0.003). Approximately 80% of the enrolled participants in both groups were still using CPAP at the end of the study; 23.3% of REM-only OSA patients met the criteria for good adherence (>4 hours/day), and 56.7% met the criteria for partial adherence. Conclusions CPAP adherence is lower among patients with REM-only OSA compared to patients with non-stage specific OSA.
Interactions between Climate and Local Air Pollution Policies: The Case of European Passenger Cars

Many European countries have adopted carbon dioxide–based (CO2-based) vehicle taxes to help reduce transportation sector emissions. The literature has shown that these policies reduce CO2 emissions but has not considered whether they affect emissions that harm local air quality. This paper analyzes whether CO2-based taxes have an unintended consequence of raising emissions of nitrogen oxides (NOx) and particulates, which harm local air quality. Using highly detailed data on European new vehicle registrations from 2002 through 2010, I estimate the effects of fuel costs and vehicle taxes on consumer vehicle choices. The CO2-based vehicle taxes reduce CO2 emissions but increase NOx and particulates emissions. The environmental harms from the NOx and particulates emissions roughly offset the benefits of the lower CO2 emissions. Because of the estimated substitution patterns, fuel-based CO2 taxes introduce milder trade-offs than do vehicle taxes.
Exchanging the Yellow Fever Virus Envelope Proteins with Modoc Virus prM and E Proteins Results in a Chimeric Virus That Is Neuroinvasive in SCID Mice

ABSTRACT A chimeric flavivirus infectious cDNA was constructed by exchanging the premembrane (prM) and envelope (E) genes of the yellow fever virus vaccine strain 17D (YF17D) with the corresponding genes of Modoc virus (MOD). This latter virus belongs to the cluster of the “not-known vector” flaviviruses and is, unlike YF17D, neuroinvasive in SCID mice. Replication of in vitro-transcribed RNA from this chimeric flavivirus was shown by [3H]uridine labeling and RNA analysis. Expression of the MOD prM and E proteins was monitored by radioimmunoprecipitation and revealed that the MOD proteins were correctly and efficiently produced from the chimeric precursor protein. The MOD E protein was shown to be N-linked glycosylated, whereas prM, as predicted from the genome sequence, did not contain N-linked carbohydrates. In Vero cells, the chimeric virus replicated with a similar efficiency as the parental viruses, although it formed smaller plaques than YF17D and MOD. In SCID mice that had been infected intraperitoneally with the chimeric virus, the viral load increased steadily until death. The MOD/YF virus, like MOD from which it had acquired the prM and E structural proteins, but unlike YF, proved neuroinvasive in SCID mice. Animals developed neurological symptoms about 15 days after inoculation and died shortly thereafter. The distribution of MOD/YF RNA in the brain of infected mice was similar to that observed in MOD-infected mice. The observations provide compelling evidence that the determinants of neuroinvasiveness of flaviviruses are entirely located in the envelope proteins prM and E.
Neutral amino acid transport at the human blood-brain barrier.

Transport regulates nutrient availability in the brain, and many pathways of brain amino acid metabolism are influenced by precursor supply. Therefore, amino acid transport through the blood-brain barrier (BBB) plays an important rate-affecting role in brain metabolism. Information on the Km of BBB amino acid transport provides the quantitative basis for understanding the physiological importance of BBB transport competition effects. For example, the uniquely low Km values of BBB amino acid transport as compared to other organs in the rat provides the basis for the selective vulnerability of the rat brain to changes in amino acid supply caused by nutritional factors. The development of amino acid imbalances in the human brain in parallel with amino acid imbalances in blood is likely to occur if the Km of BBB neutral amino acid transport in humans is low, e.g., 25-100 microM, as is the case for the rat. A new model system of the human BBB, the isolated human brain capillary, has been developed. Recent studies with this system indicate that the Km of phenylalanine transport into human brain microvessels is approximately the same as that found during in vivo studies with laboratory rats. These results support the emerging hypothesis that the human brain, like the rat brain, is subject to acute regulation by dietary-related amino acid imbalances, and that the major site of this regulation is the amino acid transport system at the BBB.
Why learning is central to sustained innovation

The term lean product development is relatively new, but the underlying concepts have been around for more than three decades. Operational excellence is not achieved by just applying so-called lean practices to every process. More than anything, it requires cultivating an aptitude and an expectation for continuous improvement within every employee. People, not processes, make great products. Rather than being a state, lean is really a process by which companies can simultaneously improve product design, manufacturing capability, and supply chain efficiency. In new product development, lean is about advancing developer skills through technical training and methods of collaboration so that each developer is able to design, develop, and deliver better products and services. What lean does try to specify are the things that should be fixed and the things that should be flexible. By making these determinations early, engineers know where they have flexibility and where they must operate within fixed constraints.
Network meta‐analysis of lorcaserin and oral hypoglycaemics for patients with type 2 diabetes mellitus and obesity

In addition to weight loss, randomized controlled trials have shown improvement in glycaemic control in patients taking lorcaserin. The aim of this study aim was to compare adding lorcaserin or other glucose lowering medications to metformin on weight and glycaemic control. A systematic review and network meta‐analysis of randomized controlled trials were conducted. Included studies (published 1990–2014) were of lorcaserin or glucose lowering medications in type 2 diabetic patients compared to placebo or different active treatments. Studies had to report ≥1 key outcome (change in weight or HbA1c, % HbA1c <7, hypoglycaemia). Direct meta‐analysis was performed using DerSimonian and Laird random effects models, and network meta‐analysis with Bayesian Markov‐chain Monte Carlo random effects models; 6552 articles were screened and 41 included. Lorcaserin reduced weight significantly more than thiazolidinediones, glinides, sulphonylureas and dipeptidyl peptidase‐4 inhibitors, some of which may have led to weight gain. There were no significant differences in weight change between lorcaserin and alpha‐glucoside inhibitors, glucagon‐like peptide‐1 agonists and sodium/glucose cotransporter 2 inhibitors. Network meta‐analysis showed lorcaserin was non‐inferior to all other agents on HbA1c reduction and % achieving HbA1c of <7%. The risk of hypoglycaemia was not significantly different among studied agents except that sulphonylureas were associated with higher risk of hypoglycaemia than lorcaserin. Although additional studies are needed, this analysis suggests in a population of patients with a body mas index of ≥27 who do not achieve glycaemic control on a single agent, lorcaserin may be added as an alternative to an add‐on glucose lowering medication.
A new Pseudomonas vaccine: Preliminary trial on human volunteers

SUMMARY Fifteen healthy volunteers were given three weekly subcutaneous injections of a new polyvalent Pseudomonas aeruginosa vaccine (PEV-01). Four doses – 1·0 RHD (manufacturer's recommended human dose), 0·75 RHD, 0·5 RHD and 0·1 RHD – were used in separate groups of volunteers. Blood samples taken before each of the injections and one taken 7 days after the last injection were examined for immune response to the vaccine and for possible adverse clinical, biochemical and haematological effects. Raised titres of antibody in serum of volunteers given 0·5–1·0 RHD vaccine were shown, often by the seventh day, in passive haemagglutination tests against all of the 16 serotypes of Ps. aeruginosa represented in the vaccine; serum from volunteers who received 0·1 RHD usually showed a reduced antibody titre. Tests of mouse protection by serum against intraperitoneal challenge with Ps. aeruginosa P14 showed increased titres of mouse protective antibody in the blood of volunteers given 1·0, 0·75 or 0·5 RHD of vaccine but a reduced mouse-protective titre in two out of three sera from volunteers given 0·1 RHD vaccine. There was a suggestion of enhanced phagocytic ingestion and intracellular killing of two strains of Ps. aeruginosa by the blood of vaccinated volunteers, and more definite enhancement of ingestion of inert latex particles, which were less well ingested than were the bacterial cells by phagocytes from unvaccinated volunteers. Apart from slight or moderate local reactions and a transient rise of temperature in some volunteers, there were no clinical, biochemical or haematological abnormalities in the vaccinated volunteers.
Factors determining English test score of high school students in rural Nepal

Due to globalization and internationalization of education, the importance of English language has been growing consistently. Like many other countries around the globe, English is taught as a compulsory subject from the primary level in Nepal. Despite continuous public and private efforts, achievement in English education is not satisfactory, especially in rural areas, due to numerous socio-cultural and other factors. Thus, this article explores some important determinants of English achievement of high school students in Rural Nepal. Through the questionnaire responses of 407 students from the four villages of Sindhupalchok district, which is explored using Cremer’s V analysis, a strong association between students' English test score and their socio-cultural, family, school and personal factors was found.
Tourism growth and income inequality: does Kuznets Curve hypothesis exist in top tourist arrival countries

ABSTRACT This study examines the relationship between tourism and the income inequality in top 43 tourist arrival countries by using the data over the period of 1995–2015. We have applied advanced econometric techniques which include cross-sectional augmented IPS (CIPS) unit root test, bootstrap co-integration, Pedroni co-integration, fully modified ordinary least squares, and heterogeneous panel causality technique. The results confirm that all the variables are co-integrated in the long run. The result also shows that the tourism has a positive effect on income inequality in full and the region-wise sample. Furthermore, the Kuznets curve hypothesis is also tested and found its existence. This concludes that if the examined countries increase their tourism revenue this will help them to reduce income inequality. This study gives valuable policy implications for the government and the policy-makers.
Sustained activation of c‐jun‐N‐terminal kinase plays a critical role in arsenic trioxide‐induced cell apoptosis in multiple myeloma cell lines

Multiple myeloma (MM) is a presently incurable B‐cell malignancy, and newer biologically based therapies are needed. Arsenic trioxide (ATO) has been established as a therapeutic agent for relapsed acute promyelocytic leukemia patients, and has been used for MM patients in clinical trials. In this study, we investigated the role of c‐jun‐N‐terminal kinase (JNK) in ATO‐induced apoptosis in MM lines. The exogenous interleukin (IL)‐6 dependent MM line, ILKM‐3, and independent MM lines, U266 and XG‐7, were treated with a therapeutic concentration of ATO with or without JNK inhibitor 1 (a JNK‐specific inhibitor) and anisomycin (a JNK activator). Their cell growth, cell cycle, JNK activation and NF‐κB activation were investigated. ATO induced apoptosis in U266 and ILKM‐3 regardless of their exogenous IL‐6 dependency. This apoptosis, accompanied with decreased mitochondrial transmembrane potential, sustained activation of JNK but not cell cycle arrest. Pretreatment of JNK inhibitor prevented ATO‐induced apoptosis in ATO‐sensitive lines. Combined treatment with ATO and anisomycin induced sustained activation of JNK and apoptosis in the ATO‐insensitive MM line, XG‐7. Results of various time period treatments of ATO showed that sustained activation of JNK was needed in ATO‐induced apoptosis in MM. IkBα phosphorylation was not associated with ATO‐sensitivity of MM lines. These findings suggest that sustained activation of JNK plays a critical role in ATO‐induced apoptosis in MM cell lines. Cotreatment with ATO and the agent, which can induce sustained activation of JNK, might improve the outcome in MM therapy. (Cancer Sci 2006; 97)
Brief Report: The Effect of Antiretroviral Therapy and CD4 Count on Markers of Infectiousness in HIV-Associated Tuberculosis

Abstract:Clinical features of tuberculosis influence infectiousness. This cross-sectional study examined the effect of combination antiretroviral therapy (cART) and CD4 on sputum smear-positivity (SS+) and pulmonary cavitation among 1589 (1185/1589 HIV-positive) miners in South Africa. Proportions SS+ varied nonlinearly by CD4 with greatest proportions SS+ (55.3%) in the lowest stratum (<100 cells/&mgr;L). Adjusted prevalence ratio for SS+; on vs. off cART was 0.90 (95% confidence interval: 0.73 to 1.11). Proportions with cavitation varied linearly with CD4, with no independent cART effect (adjusted prevalence ratio 1.17; 95% confidence interval: 0.80 to 1.71). cART did not independently affect SS+ or cavitation but may increase infectiousness through CD4 recovery.
Mobilized allogeneic peripheral stem/progenitor cell apheresis with Spectra Optia v.5·0, a novel, automatic interface‐controlled apheresis system: results from the first feasibility trial

Background and Objectives G‐CSF mobilized peripheral blood stem/progenitor cells are frequently used for allogeneic transplantation. Available manual apheresis systems generate stem cell products of consistently high quality. Short‐comings include need for continuous interface monitoring/adjustment, interface instability in donors with inconsistent blood flow, high collection variability, high platelet loss, and failure to electronically document apheresis parameters.
Quantifying residual ionospheric errors in GNSS radio occultation bending angles based on ensembles of profiles from end-to-end simulations

Abstract. The radio occultation (RO) technique using signals from the Global Navigation Satellite System (GNSS), in particular from the Global Positioning System (GPS) so far, is currently widely used to observe the atmosphere for applications such as numerical weather prediction and global climate monitoring. The ionosphere is a major error source in RO measurements at stratospheric altitudes, and a linear ionospheric correction of dual-frequency RO bending angles is commonly used to remove the first-order ionospheric effect. However, the residual ionospheric error (RIE) can still be significant so that it needs to be further mitigated for high-accuracy applications, especially above about 30 km altitude where the RIE is most relevant compared to the magnitude of the neutral atmospheric bending angle. Quantification and careful analyses for better understanding of the RIE is therefore important for enabling benchmark-quality stratospheric RO retrievals. Here we present such an analysis of bending angle RIEs covering the stratosphere and mesosphere, using quasi-realistic end-to-end simulations for a full-day ensemble of RO events. Based on the ensemble simulations we assessed the variation of bending angle RIEs, both biases and standard deviations, with solar activity, latitudinal region and with or without the assumption of ionospheric spherical symmetry and co-existing observing system errors. We find that the bending angle RIE biases in the upper stratosphere and mesosphere, and in all latitudinal zones from low to high latitudes, have a clear negative tendency and a magnitude increasing with solar activity, which is in line with recent empirical studies based on real RO data although we find smaller bias magnitudes, deserving further study in the future. The maximum RIE biases are found at low latitudes during daytime, where they amount to within −0.03 to −0.05 μrad, the smallest at high latitudes (0 to −0.01 μrad; quiet space weather and winter conditions). Ionospheric spherical symmetry or asymmetries about the RO event location have only a minor influence on RIE biases. The RIE standard deviations are markedly increased both by ionospheric asymmetries and increasing solar activity and amount to about 0.3 to 0.7 μrad in the upper stratosphere and mesosphere. Taking also into account the realistic observation errors of a modern RO receiving system, amounting globally to about 0.4 μrad (unbiased; standard deviation), shows that the random RIEs are typically comparable to the total observing system error. The results help to inform future RIE mitigation schemes that will improve upon the use of the linear ionospheric correction of bending angles and also provide explicit uncertainty estimates.