Chemical-free inactivated whole influenza virus vaccine prepared by ultrashort pulsed laser treatment

There is an urgent need for rapid methods to develop vaccines in response to emerging viral pathogens. Whole inactivated virus (WIV) vaccines represent an ideal strategy for this purpose; however, a universal method for producing safe and immunogenic inactivated vaccines is lacking. Conventional pathogen inactivation methods such as formalin, heat, ultraviolet light, and gamma rays cause structural alterations in vaccines that lead to reduced neutralizing antibody specificity, and in some cases, disastrous T helper type 2-mediated immune pathology. We have evaluated the potential of a visible ultrashort pulsed (USP) laser method to generate safe and immunogenic WIV vaccines without adjuvants. Specifically, we demonstrate that vaccination of mice with laser-inactivated H1N1 influenza virus at about a 10-fold lower dose than that required using conventional formalin-inactivated influenza vaccines results in protection against lethal H1N1 challenge in mice. The virus, inactivated by the USP laser irradiation, has been shown to retain its surface protein structure through hemagglutination assay. Unlike conventional inactivation methods, laser treatment did not generate carbonyl groups in protein, thereby reducing the risk of adverse vaccine-elicited T helper type 2 responses. Therefore, USP laser treatment is an attractive potential strategy to generate WIV vaccines with greater potency and safety than vaccines produced by current inactivation techniques

First- and Second-trimester Down Syndrome Screening: Current Strategies and Clinical Guidelines

SummaryDown syndrome (DS) is the most common human disease caused by a structural chromosome defect. The original screening test for DS was maternal age or a history of a previously affected infant. Maternal serum screening has been incorporated into routine prenatal checkup in Taiwan since 1994. We used free β-human chorionic gonadotropin and α-fetoprotein (double test) as the serum markers, and this was carried out between the 15 to 20th week of gestation. The overall detection rate was 56% and was compatible with studies of Caucasian populations. The impact of double tests in Taiwan has shown itself by a dramatic lowering of the rate of DS live birth from 0.63 before screening to 0.16 per 1,000 live births at present. However, because of its relatively low detection rate and poor cost-effectiveness, the double test is not justified as a routine screening tool currently. First-trimester combined test is now becoming more widely available and provides increased sensitivity when detecting DS; it has a detection rate of approximately 85% with a false-positive rate of 5%. Nuchal translucency measurement requires ongoing quality control and sufficient certificated obstetricians; therefore, first-trimester ultrasound is limited only in designated centers. The quadruple test, having comparable detection rate, should be considered for incorporation into second-trimester screening in Taiwan in the near future. Other screening approaches and combinations have also been utilized in the Western countries. In this review, we outline the various options with respect to DS screening and hope that this will provide practical information for physicians offering such screenings. [Taiwan J Obstet Cynecol 2008;47(2):157-1 62

“I can’t see an end in sight.” How the COVID-19 pandemic may influence suicide risk: a qualitative study

<jats:p> Zusammenfassung: Theoretischer Hintergrund: Das Ziel der vorliegenden Studie war es, eine deutschsprachige Adaptation der Bergen Study Addiction Scale (BStAS), einer Skala zur Erfassung von exzessivem Studierverhalten, zu entwickeln und zu validieren. Methode: Die Daten von 615 Studierenden wurden analysiert. Die Dimensionalität der BStAS wurde mittels konfirmatorischer Faktorenanalyse überprüft. Außerdem wurden Korrelations- und hierarchische Regressionsanalysen durchgeführt, um Zusammenhänge von exzessivem Studierverhalten mit Persönlichkeit und Gesundheit zu untersuchen. Ergebnisse: Der Vergleich mit Dynamic Fit Index Cutoffs deutete auf eine moderate Missspezifikation des einfaktoriellen Modells hin. Wie erwartet war exzessives Studierverhalten positiv mit wöchentlichen Lernstunden, Neurotizismus, wahrgenommenem Stress, psychosomatischen Beschwerden und Schlafproblemen assoziiert und hing negativ mit Lebenszufriedenheit zusammen. Schlussfolgerung: Es ist fraglich, ob alle Items der BStAS Aspekte einer Verhaltenssucht erfassen. Die Ergebnisse legen dennoch nahe, dass die BStAS ein Studierverhalten misst, das in Bezug auf physische und psychische Gesundheit von Relevanz ist. </jats:p&gt

Identification of novel DNA methylation inhibitors via a two-component reporter gene system

<p>Abstract</p> <p>Background</p> <p>Targeting abnormal DNA methylation represents a therapeutically relevant strategy for cancer treatment as demonstrated by the US Food and Drug Administration approval of the DNA methyltransferase inhibitors azacytidine and 5-aza-2'-deoxycytidine for the treatment of myelodysplastic syndromes. But their use is associated with increased incidences of bone marrow suppression. Alternatively, procainamide has emerged as a potential DNA demethylating agent for clinical translation. While procainamide is much safer than 5-aza-2'-deoxycytidine, it requires high concentrations to be effective in DNA demethylation in suppressing cancer cell growth. Thus, our laboratories have embarked on the pharmacological exploitation of procainamide to develop potent DNA methylation inhibitors through lead optimization.</p> <p>Methods</p> <p>We report the use of a DNA methylation two-component enhanced green fluorescent protein reporter system as a screening platform to identify novel DNA methylation inhibitors from a compound library containing procainamide derivatives.</p> <p>Results</p> <p>A lead agent IM25, which exhibits substantially higher potency in <it>GSTp1 </it>DNA demethylation with lower cytotoxicity in MCF7 cells relative to procainamide and 5-aza-2'-deoxycytidine, was identified by the screening platform.</p> <p>Conclusions</p> <p>Our data provide a proof-of-concept that procainamide could be pharmacologically exploited to develop novel DNA methylation inhibitors, of which the translational potential in cancer therapy/prevention is currently under investigation.</p

A 9 bp cis-element in the promoters of class I small heat shock protein genes on chromosome 3 in rice mediates L-azetidine-2-carboxylic acid and heat shock responses

In rice, the class I small heat shock protein (sHSP-CI) genes were found to be selectively induced by L-azetidine-2-carboxylic acid (AZC) on chromosome 3 but not chromosome 1. Here it is shown that a novel cis-responsive element contributed to the differential regulation. By serial deletion and computational analysis, a 9 bp putative AZC-responsive element (AZRE), GTCCTGGAC, located between nucleotides –186 and –178 relative to the transcription initiation site of Oshsp17.3 was revealed. Deletion of this putative AZRE from the promoter abolished its ability to be induced by AZC. Moreover, electrophoretic mobility shift assay (EMSA) revealed that the AZRE interacted specifically with nuclear proteins from AZC-treated rice seedlings. Two AZRE–protein complexes were detected by EMSA, one of which could be competed out by a canonical heat shock element (HSE). Deletion of the AZRE also affected the HS response. Furthermore, transient co-expression of the heat shock factor OsHsfA4b with the AZRE in the promoter of Oshsp17.3 was effective. The requirement for the putative AZRE for AZC and HS responses in transgenic Arabidopsis was also shown. Thus, AZRE represents an alternative form of heat HSE, and its interaction with canonical HSEs through heat shock factors may be required to respond to HS and AZC

Low Cost Seismic Network Practical Applications for Producing Quick Shaking Maps in Taiwan

Two major earthquakes of ML greater than 6.0 occurred in Taiwan in the first half of 2013. The vibrant shaking brought landslides, falling rocks and casualties. This paper presents a seismic network developed by National Taiwan University (NTU) with 401 Micro-Electro Mechanical System (MEMS) accelerators. The network recorded high quality strong motion signals from the two events and produced delicate shaking maps within one minute after the earthquake occurrence. The high shaking regions of the intensity map produced by the NTU system suggest damage and casualty locations. Equipped with a dense array of MEMS accelerometers, the NTU system is able to accommodate 10% signals loss from part of the seismic stations and maintain its normal functions for producing shaking maps. The system also has the potential to identify the rupture direction which is one of the key indices used to estimate possible damage. The low cost MEMS accelerator array shows its potential in real-time earthquake shaking map generation and damage avoidance

A Comprehensive Survey of Data Mining-based Fraud Detection Research

This survey paper categorises, compares, and summarises from almost all published technical and review articles in automated fraud detection within the last 10 years. It defines the professional fraudster, formalises the main types and subtypes of known fraud, and presents the nature of data evidence collected within affected industries. Within the business context of mining the data to achieve higher cost savings, this research presents methods and techniques together with their problems. Compared to all related reviews on fraud detection, this survey covers much more technical articles and is the only one, to the best of our knowledge, which proposes alternative data and solutions from related domains.Comment: 14 page

On the selection and design of proteins and peptide derivatives for the production of photoluminescent, red-emitting gold quantum clusters

Novel pathways of the synthesis of photoluminescent gold quantum clusters (AuQCs) using biomolecules as reactants provide biocompatible products for biological imaging techniques. In order to rationalize the rules for the preparation of red-emitting AuQCs in aqueous phase using proteins or peptides, the role of different organic structural units was investigated. Three systems were studied: proteins, peptides, and amino acid mixtures, respectively. We have found that cysteine and tyrosine are indispensable residues. The SH/S-S ratio in a single molecule is not a critical factor in the synthesis, but on the other hand, the stoichiometry of cysteine residues and the gold precursor is crucial. These observations indicate the importance of proper chemical behavior of all species in a wide size range extending from the atomic distances (in the AuI-S semi ring) to nanometer distances covering the larger sizes of proteins assuring the hierarchical structure of the whole self-assembled system

Improvement of Carbon Tetrachloride-Induced Acute Hepatic Failure by Transplantation of Induced Pluripotent Stem Cells without Reprogramming Factor c-Myc

The only curative treatment for hepatic failure is liver transplantation. Unfortunately, this treatment has several major limitations, as for example donor organ shortage. A previous report demonstrated that transplantation of induced pluripotent stem cells without reprogramming factor c-Myc (3-genes iPSCs) attenuates thioacetamide-induced hepatic failure with minimal incidence of tumorigenicity. In this study, we investigated whether 3-genes iPSC transplantation is capable of rescuing carbon tetrachloride (CCl4)-induced fulminant hepatic failure and hepatic encephalopathy in mice. Firstly, we demonstrated that 3-genes iPSCs possess the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that exhibit biological functions and express various hepatic specific markers. 3-genes iPSCs also exhibited several antioxidant enzymes that prevented CCl4-induced reactive oxygen species production and cell death. Intraperitoneal transplantation of either 3-genes iPSCs or 3-genes iPSC-Heps significantly reduced hepatic necrotic areas, improved hepatic functions, and survival rate in CCl4-treated mice. CCl4-induced hepatic encephalopathy was also improved by 3-genes iPSC transplantation. Hoechst staining confirmed the successful engraftment of both 3-genes iPSCs and 3-genes iPSC-Heps, indicating the homing properties of these cells. The most pronounced hepatoprotective effect of iPSCs appeared to originate from the highest antioxidant activity of 3-gene iPSCs among all transplanted cells. In summary, our findings demonstrated that 3-genes iPSCs serve as an available cell source for the treatment of an experimental model of acute liver diseases

Intermediate-band Surface Photometry of the Edge-on Galaxy: NGC 4565

We present a deep, 42.79 hr image of the nearby, edge-on galaxy NGC 4565 in the Beijing-Arizona-Taipei-Connecticut (BATC) 6660A band using the large-format CCD system on the 0.6m Schmidt telescope at the Xinglong Station of the National Astronomical Observatories of China (NAOC). we obtain a final image that is calibrated to an accuracy of 0.02 mag in zero point, and for which we can measure galaxy surface brightness to an accuracy of 0.25 mag at a surface brightness at 27.5 mag arcsec^-2 at 6660A, corresponding to a distance of 22 kpc from the center of the disk. The integrated magnitude of NGC4565 in our filter is m6660=8.99 (R magnitude of 9.1) to a surface brightness of 28 mag arcsec-2. We analyze the faint outer parts of this galaxy using a two-dimensional model comprised of three components: an exponential thin disk, an exponential thick disk, and a power-law halo. A total of 12 parameters are included in our model. We determine the best values of our model parameters via 10,000 random initial values, 3,700 of which converge to final values. The thin disk and thick disk parameters we determine here are consistent with those of previous studies of this galaxy. However, our very deep image permits a better determination of the power law fit to the halo, constraining this power law to be between r^-3.2 and r^-4.0, with a best fit value of r^-3.88. We find the axis ratio of the halo to be 0.44 and its core radius to be 14.4 kpc (for an adopted distance of 14.5 Mpc).Comment: 34 pages, 11 figures, will appear in March 2002 of A