Miracle-dz/UniFAR-FTUs huggingface dataset:
Rational design of a flavivirus vaccine through abolishing 1 viral RNA 2 ′-O methylation

8 Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 9 100071, China; State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, 10 China; Novartis Institute for Tropical Diseases, Singapore; Center for Biomaterials 11 and Biopathways, Department of Chemistry, Zhejiang University, Hangzhou 310027, 12 China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese 13 Academy of Science, Wuhan 430071, China; Shanghai Institute for Pasteur, Chinese 14 Academy of Science, Shanghai, China; Singapore Immunology Network, ASTAR 15 (Agency for Science, Technology and Research), Singapore 16
Simplified method for confirmation of PCR products.

The products of polymerase chain reaction (PCR) (1) are usually visualized by agarose or polyacrylamide gel electrophoresis followed by ethidium bromide staining. However, depending on the purpose of experiment, it sometimes needs to be shown whether the amplified DNA originated from target region or not. In that case a labelled oligonucleotide probe complementary to an appropriate internal sequence between the two normal primers is prepared and used as a probe for Southern hybridization (2). Another method uses a second PCR with another primer in the target sequence (3). The product is verified by restriction endonuclease digestion. However, confirmation by these methods is time-consuming, especially the Southern hybridization analysis. A new method of PCR using three primers is demonstrated in the present report. Amplification of DNA was performed based on the method described by Saiki et al. (1). Template DNAs were isolated from Mycoplasma hominis, M.pneumoniae, and Escherichia coli by the method of Marmur (4). Primers were obtained from 3 regions in 16S ribosomal RNA (rRNA) sequence of Mycoplasma species (Fig. 1). Two primers, B-1 and Mp-7, were demonstrated to be well-conserved regions among many bacterial 16S rRNAs (5), and used as outer primers in the present study. An inside primer, Mp-6, was shown to be specific for M.pneumoniae. A 50 Al of reaction buffer (10 mM Tris-Cl, 50 mM KCI, 1.5 mM MgCl2, 0.01% gelatin, pH 8.3) containing 200 ,iM dNTPs, 100 ng of template DNA, 2.5 units Taq polymerase (Stratagene, California, USA) and 1 AM outer primers
Proton pump inhibitors: predisposers to Alzheimer disease?

The abnormal processing of amyloid‐β peptide (Aβ) and resultant formation of fibrillar Aβ (fAβ) are major events in the pathogenesis of Alzheimer disease (AD). Microglia as the phagocytic cells of the brain can engulf and digest fAβ within their acidic lysosomes. The lysosomes of AD patients are less acidic and therefore less capable of clearance of fAβ. Vacuolar proton pumps (V‐ATPases) which are found abundantly in microglia and macrophages, acidify lysosomes by pumping protons into these structures. Proton pump inhibitors (PPIs) can inhibit V‐ATPases of the lysosomes. These drugs are shown to penetrate the blood–brain barrier in animals. PPIs are consumed for long periods in conditions such as gastroesophageal reflux disease, with the resultant exposure of the human brain to the substantial amounts of PPIs. We hypothesize that by blocking the V‐ATPases on microglial lysosomes, PPIs may basify lysosomes and hamper degradation of fAβ. Chronic consumption of PPIs may thus be a risk factor for AD.
Evaluation of an intervention aimed at improving voluntary incident reporting in hospitals

Objectives: To assess the effectiveness of an intervention package comprising intense education, a range of reporting options, changes in report management and enhanced feedback, in order to improve incident-reporting rates and change the types of incidents reported. Design, setting and participants: Non-equivalent group controlled clinical trial involving medical and nursing staff working in 10 intervention and 10 control units in four major cities and two regional hospitals in South Australia. Main outcome measures: Comparison of reporting rates by type of unit, profession, location of hospital, type of incident reported and reporting mechanism between baseline and study periods in control and intervention units. Results: The intervention resulted in significant improvement in reporting in inpatient areas (additional 60.3 reports/10 000 occupied bed days (OBDs); 95% CI 23.8 to 96.8, p<0.001) and in emergency departments (EDs) (additional 39.5 reports/10 000 ED attendances; 95% CI 17.0 to 62.0, p<0.001). More reports were generated (a) by doctors in EDs (additional 9.5 reports/10 000 ED attendances; 95% CI 2.2 to 16.8, p = 0.001); (b) by nurses in inpatient areas (additional 59.0 reports/10 000 OBDs; 95% CI 23.9 to 94.1, p<0.001) and (c) anonymously (additional 20.2 reports/10 000 OBDs and ED attendances combined; 95% CI 12.6 to 27.8, p<0.001). Compared with control units, the study resulted in more documentation, clinical management and aggression-related incidents in intervention units. In intervention units, more reports were submitted on one-page forms than via the call centre (1005 vs 264 reports, respectively). Conclusions: A greater variety and number of incidents were reported by the intervention units during the study, with improved reporting by doctors from a low baseline. However, there was considerable heterogeneity between reporting rates in different types of units.
Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia.

PURPOSE Troxacitabine has activity in refractory myeloid leukemia, either as a single agent or when combined with cytarabine (ara-C) or with idarubicin. A prospective, randomized study was conducted in patients aged 50 years or older with untreated, adverse karyotype, acute myeloid leukemia (AML) to assess troxacitabine-based regimes as induction therapy. PATIENTS AND METHODS Patients were randomized to receive idarubicin and ara-C (IA) versus troxacitabine and ara-C (TA) versus troxacitabine and idarubicin (TI). A Bayesian design was used to adaptively randomly assign patients to treatment. Thus, although there was initially an equal chance for randomization to IA, TA, or TI, treatment arms with a higher success rate progressively received a greater proportion of patients. RESULTS Thirty-four patients were treated. Randomization to TI stopped after five patients and randomization to TA stopped after 11 patients. Defining success as complete remission (CR) that occurred within 49 days of starting treatment, success rates were 55% (10 of 18 patients) with IA, 27% (three of 11 patients) with TA, and 0% (zero of five patients) with TI. Because three CRs occurred after day 49, final CR rates were 55% (10 of 18 patients) with IA, 45% (five of 11 patients) with TA, and 20% (one of five patients) with TI. The probability that TA was inferior to IA was 70%, with a 5% probability that TA would have a 20% higher CR rate than IA. Survival was equivalent with all three regimens. CONCLUSION Neither troxacitabine combination was superior to IA in elderly patients with previously untreated adverse karyotype AML.
The treatment of diabetic gastroparesis with botulinum toxin

OBJECTIVE Gastroparesis is a disorder of delayed gastric emptying that is often chronic in nature. Up to 50% of type 1 diabetic subjects have symptoms of gastroparesis, which include nausea, vomiting, and early satiety. Elevated pyloric pressures may be responsible for delayed gastric emptying in diabetic subjects. Botulinum toxin inhibits the release of acetylcholine and produces transient paralysis when injected into smooth muscle. The aim of this study was to determine whether injection of the pylorus with botulinum toxin in patients with diabetic gastroparesis improves symptoms of gastroparesis, alters gastric emptying scan time, and/or changes weight and insulin use. RESEARCH DESIGN AND METHODS This was an open-label trial with age- and sex-matched control subjects from a tertiary care referral center for patients with gastroparesis. Eight type 1 diabetic subjects (six women and two men; mean age 41 years; mean years with diabetes 25.3) who had failed standard therapy were enrolled. Intervention consisted of injection of the pylorus with 200 units of botulinum toxin during upper endoscopy. Symptoms, antropyloric manometry, gastric emptying scan times, weight, and insulin use were all recorded before intervention and during a 12-week follow-up period. RESULTS Seven of the eight patients completed the full 12-week follow-up period. No complications were noted. Mean symptom scores declined from 27 to 12.1 (P < 0.01), whereas the SF-36 physical functioning domain also improved (P < 0.05). Four patients noted an increase in insulin use of >5 units/day. Six of the seven patients gained weight (P = 0.05). Gastric emptying scan time improved in four patients. CONCLUSIONS Botulinum toxin injection of the pylorus is safe and improves symptoms in patients with diabetic gastroparesis. These results warrant further investigation with a large, double-blind, placebo-controlled trial.
Functional Differences Between Growth Plate Apoptotic Bodies and Matrix Vesicles

Mineralization often occurs in areas of apoptotic changes. Our findings indicate that physiological mineralization is mediated by matrix vesicles. These matrix vesicles use mechanisms to induce mineralization that are different from the mechanisms used by apoptotic bodies released from apoptotic cells. Therefore, different therapeutic approaches must be chosen to inhibit pathological mineralization depending on the mechanism of mineralization (matrix vesicles versus apoptotic bodies).
Sister Chromatid Exchanges Are Mediated by Homologous Recombination in Vertebrate Cells

ABSTRACT Sister chromatid exchange (SCE) frequency is a commonly used index of chromosomal stability in response to environmental or genetic mutagens. However, the mechanism generating cytologically detectable SCEs and, therefore, their prognostic value for chromosomal stability in mitotic cells remain unclear. We examined the role of the highly conserved homologous recombination (HR) pathway in SCE by measuring SCE levels in HR-defective vertebrate cells. Spontaneous and mitomycin C-induced SCE levels were significantly reduced for chicken DT40 B cells lacking the key HR genes RAD51 and RAD54but not for nonhomologous DNA end-joining (NHEJ)-defectiveKU70−/− cells. As measured by targeted integration efficiency, reconstitution of HR activity by expression of a human RAD51 transgene restored SCE levels to normal, confirming that HR is the mechanism responsible for SCE. Our findings show that HR uses the nascent sister chromatid to repair potentially lethal DNA lesions accompanying replication, which might explain the lethality or tumorigenic potential associated with defects in HR or HR-associated proteins.
Ionizing Radiation Damage to the Folded Chromosome of Escherichia coli K-12: Repair of Double-Strand Breaks in Deoxyribonucleic Acid

The extremely gentle lysis and unfolding procedures that have been developed for the isolation of nucleoid deoxyribonucleic acid (DNA; K. M. Ulmer et al., J. Bacteriol. 138:475–485, 1979) yield undamaged, replicating genomes, thus permitting direct measurement of the formation and repair of DNA double-strand breaks at biologically significant doses of ionizing radiation. Repair of ionizing radiation damage to folded chromosomes of Escherichia coli K-12 strain AB2497 was observed within 2 to 3 h of post-irradiation incubation in growth medium. Such behavior was not observed after post-irradiation incubation in growth medium of a recA13 strain (strain AB2487). A model based on recombinational repair is proposed to explain the formation of 2,200 to 2,300S material during early stages of incubation and to explain subsequent changes in the gradient profiles. Association of unrepaired DNA with the plasma membrane is proposed to explain the formation of a peak of rapidly sedimenting material (greater than 3,100S) during the later stages of repair. Direct evidence of repair of double-strand breaks during post-irradiation incubation in growth medium was obtained from gradient profiles of DNA from ribonuclease-digested chromosomes. The sedimentation coefficient of broken molecules was restored to the value of unirradiated DNA after 2 to 3 h of incubation, and the fraction of the DNA repaired in this fashion was equal to the fraction of cells that survived at the same dose. An average of 2.7 double-strand breaks per genome per lethal event was observed, suggesting that one to two double-strand breaks per genome are repairable in E. coli K-12 strain AB2497.
Dorsal hand vein Biometric authentication using complex Walsh transform

People are depending on information very much and it is becoming essential to carry out different activities every day. The degree of security in many situations becoming critical and need to be paid attention because of increase of crime rate with sophisticated technology. To increase the privacy and safety of information care must be taken to protect the information. Individual authentication is achieved using Biometric traits in different fields. As biometric authentication, there are methods using finger print, iris, and voice and so on. For the disadvantages of other biometric recognition methods, dorsal hand vein pattern has emerged as new biometric because the vascular structure is unique to every individual. The vein is the inner features of body and can't be fabricated and they are lasting. So it can be used for identification of individuals in highly secured areas. In this project, a new approach is proposed for extracting critical features from the dorsal hand vein pattern using the concepts of Walsh transform and Euclidean distance similarity measure. The proposed methodology has been tested on a dataset of 100 dorsal hand vein images and the experimental results are found to be promising.
Small-animal and endoscopic PET detector modules based on multichannel digital silicon photomultipliers

In time-of-flight (TOF) positron emission tomography (PET), the coincidence resolving time (CRT) has a strong influence on the overall performance. Multichannel digital silicon photomultipliers (MD-SiPMs) are able to obtain several timestamps for gamma photon timemark estimation. Using this feature, the CRT is improved and the system robustness is significantly increased by utilizing multiple photoelectron timestamps. In addition, the PET instrumentation chain is simplified because of the intrinsic digitization and integrated functionality of the MD-SiPM. The main objective of this work is to demonstrate the possibility of building a complete highly-miniaturized PET detector module for endoscopic applications. In addition, we show that it's possible to operate simultaneously several MD-SiPM array chips in order to build a small-animal PET detector modules. We present the implementation of two PET detector modules that are based on MD-SiPMs: a small animal and an endoscopic PET detector modules. The small animal PET detector module consists of 2×4 monolithic MD-SiPM array chips. In addition, this module includes a low-cost field programmable gate array (FPGA), a temperature controlling system and data transfer interfaces. The endoscopic PET detector module comprises a single monolithic array of 9×18 MD-SiPM and a small form-factor FPGA. In this module, a remarkable level of compactness is achieved. Eventually, a thermal characterization and a preliminary radiation measurement are presented.
“Starkfest” Vision and Clinic Science Special Issue: Abnormal Transient Myopia in Symptomatic Individuals after Sustained Nearwork

After a sustained period of nearwork, some patients report slightly blurred distance vision for several seconds or even minutes. This presumed large and prolonged “abnormal transient myopia” has never been objectively documented. A Canon R-1 infrared autorefractor was used to assess distance refractive state every 2 s before and immediately after a binocular near task in three such individuals. Results showed a large post-task myopic shift, slowed baseline decay, and increased response variability as compared with that found in asymptomatic visually normal individuals. These findings suggested that this transient distance blur was related to the increased transient myopia resulting from one or more possible abnormalities related to the accommodative system.
Smoke intake among smokers is higher in lower socioeconomic groups

OBJECTIVE To analyse socioeconomic differences in serum thiocyanate concentrations among current smokers, and whether such differences persist after adjustment for the number of cigarettes smoked. SETTING General population of six districts of the Czech Republic in 1992. PARTICIPANTS 451 male and 282 female current smokers. MAIN OUTCOME MEASURE Serum concentration of thiocyanate. RESULTS There was a clear educational gradient in serum thiocyanate among male smokers; car ownership and crowding were not related to thiocyanate. Age adjusted mean concentrations in men with primary, vocational, secondary, and university education were 168.6, 158.2, 148.2, and 141.8 μmol/l, respectively (p for trend 0.032). Adjustment for the average daily number of cigarettes explained a part of this gradient. Socioeconomic differences in serum thiocyanate were not seen in women. CONCLUSION The strong gradient in men suggests that smokers from lower socioeconomic groups have a preference for higher smoke intake and so may be more nicotine dependent. This finding, if confirmed, would have important implications for anti-smoking programmes.
Functional Balancing of the Hypoxia Regulators RAP2.12 and HRA1 Takes Place in vivo in Arabidopsis thaliana Plants

Plants are known to respond to variations in cellular oxygen availability and distribution by quickly adapting the transcription rate of a number of genes, generally associated to improved energy usage pathways, oxygen homeostasis and protection from harmful products of anaerobic metabolism. In terrestrial plants, such coordinated gene expression program is promoted by a conserved subfamily of ethylene responsive transcription factors called ERF-VII, which act as master activators of hypoxic gene transcription. Their abundance is directly regulated by oxygen through a mechanism of targeted proteolysis present under aerobic conditions, which is triggered by ERF-VII protein oxidation. Beside this, in Arabidopsis thaliana, the activity of the ERF-VII factor RAP2.12 has been shown to be restrained and made transient by the hypoxia-inducible transcription factor HRA1. This feedback mechanism has been proposed to modulate ERF-VII activity in the plant under fluctuating hypoxia, thereby enhancing the flexibility of the response. So far, functional balancing between RAP2.12 and HRA1 has been assessed in isolated leaf protoplasts, resulting in an inverse relationship between HRA1 amount and activation of RAP2.12 target promoters. In the present work, we showed that HRA1 is effective in balancing RAP2.12 activity in whole arabidopsis plants. Examination of a segregating population, generated from RAP2.12 and HRA1 over-expressing plants, led to the first quantitative proof that, over a range of either transgene expression levels, HRA1 counteracts the phenotypic and transcriptional effects of RAP2.12. This report supports the occurrence of fine-tuned regulation of the hypoxic response under physiological growth conditions.
Depression of Atrioventricular Sensitivity in the Dog by Successive Brief Bursts of Vagal Stimulation

When identical, successive single vagal stimulations, separated in time (T) by 2–60 seconds, are applied in the dog, the peak change in atrioventricular conduction time for the second stimulus, ΔAV2, is less than that of the first, ΔAV1, that is, the ratio ΔAV2/ΔAV, < 1.0 (the mean minimum ΔAV2/ΔAV, = 0.52). It was further determined that at any one given T, the actual value of ΔAV2/ΔAV, also was a function of the first stimulus amplitude. The same dependence of ΔAV2/ΔAV1 on the first stimulus amplitude was found when the amplitude was varied either by (1) changing the number of vagal fibers stimulated for both the first and second response, but at a constant AD (the delay in the cardiac cycle at which the stimulus was given), or (2) by stimulating the same number of fibers but changing AD for both the first and second response. Also the same characteristic of ΔAV2/ΔAV1 plotted vs. T was found either (1) when both the first and second responses were produced by stimulation of the same nerve, or (2) when stimulation of the nerve from one side produced the first response and the alternate side the second response. These data suggest that the reason for this ΔAV2/ΔAV1 time-dependent effect lies in changes in receptor responsiveness or in acetylcholine inactivation, but not in mechanisms purely internal to the nerve terminal associated with synthesis, storage, or release of acetylcholine.
Microtubule assembly by the Apc protein is regulated by importin-β—RanGTP

Mutations in the tumour suppressor Adenomatous polyposis coli (Apc) initiate most sporadic colorectal cancers. Apc is implicated in regulating microtubule (MT) dynamics in interphase and mitosis. However, little is known about the underlying mechanism or regulation of this Apc function. We identified importin-β as a binding partner of Apc that regulates its effect on MTs. Apc binds importin-β in vitro and in Xenopus egg extracts, and RanGTP inhibits this interaction. The armadillo-like repeat domain of importin-β binds to the middle of Apc, where it can compete with β-catenin. In addition, two independent sites in the C terminus of Apc bind the N-terminal region of importin-β. Binding to importin-β reduces the ability of Apc to assemble and bundle MTs in vitro and to promote assembly of microtubule asters in Xenopus egg extracts, but does not affect the binding of Apc to MTs or to EB1. Depletion of Apc decreases the formation of cold-stable spindles in Xenopus egg extracts. Importantly, the ability of purified Apc to rescue this phenotype was reduced when it was constitutively bound to importin-β. Thus, importin-β binds to Apc and negatively regulates the MT-assembly and spindle-promoting activity of Apc in a Ran-regulatable manner.
Differential Gene Regulation by the Two Progesterone Receptor Isoforms in Human Breast Cancer Cells*

The PR-A and PR-B isoforms of progesterone receptors (PR) have different physiological functions, and their ratio varies widely in breast cancers. To determine whether the two PR regulate different genes, we used human breast cancer cell lines engineered to express one or the other isoform. Cells were treated with progesterone in triplicate, time-separated experiments, allowing statistical analyses of microarray gene expression data. Of 94 progesterone-regulated genes, 65 are uniquely regulated by PR-B, 4 uniquely by PR-A, and only 25 by both. Almost half the genes encode proteins that are membrane-bound or involved in membrane-initiated signaling. We also find an important set of progesterone-regulated genes involved in mammary gland development and/or implicated in breast cancer. This first, large scale study of PR gene regulation has important implications for the measurement of PR in breast cancers and for the many clinical uses of synthetic progestins. It suggests that it is important to distinguish between the two isoforms in breast cancers and that isoform-specific genes can be used to screen for ligands that selectively modulate the activity of PR-A or PR-B. Additionally, use of natural target genes, rather than “consensus” response elements, for transcription studies should improve our understanding of steroid hormone action.