On the complexity of trial and error for constraint satisfaction problems

In 2013 Bei, Chen and Zhang introduced a trial and error model of computing, and applied to some constraint satisfaction problems. In this model the input is hidden by an oracle which, for a candidate assignment, reveals some information about a violated constraint if the assignment is not satisfying. In this paper we initiate a systematic study of constraint satisfaction problems in the trial and error model, by adopting a formal framework for CSPs, and defining several types of revealing oracles. Our main contribution is to develop a transfer theorem for each type of the revealing oracle. To any hidden CSP with a specific type of revealing Oracle, the transfer theorem associates another CSP in the normal setting, such that their complexities are polynomial-time equivalent. This in principle transfers the study of a large class of hidden CSPs to the study of normal CSPs. We apply the transfer theorems to get polynomial-time algorithms or hardness results for several families of concrete problems. (C) 2017 Elsevier Inc. All rights reserved

Using detergent to enhance detection sensitivity of African trypanosomes in human CSF and blood by Loop-Mediated Isothermal Amplification (LAMP)

<p><b>Background:</b> The loop-mediated isothermal amplification (LAMP) assay, with its advantages of simplicity, rapidity and cost effectiveness, has evolved as one of the most sensitive and specific methods for the detection of a broad range of pathogenic microorganisms including African trypanosomes. While many LAMP-based assays are sufficiently sensitive to detect DNA well below the amount present in a single parasite, the detection limit of the assay is restricted by the number of parasites present in the volume of sample assayed; i.e. 1 per µL or 103 per mL. We hypothesized that clinical sensitivities that mimic analytical limits based on parasite DNA could be approached or even obtained by simply adding detergent to the samples prior to LAMP assay.</p> <p><b>Methodology/Principal Findings:</b> For proof of principle we used two different LAMP assays capable of detecting 0.1 fg genomic DNA (0.001 parasite). The assay was tested on dilution series of intact bloodstream form Trypanosoma brucei rhodesiense in human cerebrospinal fluid (CSF) or blood with or without the addition of the detergent Triton X-100 and 60 min incubation at ambient temperature. With human CSF and in the absence of detergent, the LAMP detection limit for live intact parasites using 1 µL of CSF as the source of template was at best 103 parasites/mL. Remarkably, detergent enhanced LAMP assay reaches sensitivity about 100 to 1000-fold lower; i.e. 10 to 1 parasite/mL. Similar detergent-mediated increases in LAMP assay analytical sensitivity were also found using DNA extracted from filter paper cards containing blood pretreated with detergent before card spotting or blood samples spotted on detergent pretreated cards.</p> <p><b>Conclusions/Significance:</b> This simple procedure for the enhanced detection of live African trypanosomes in biological fluids by LAMP paves the way for the adaptation of LAMP for the economical and sensitive diagnosis of other protozoan parasites and microorganisms that cause diseases that plague the developing world.</p&gt

Estimation of cancer incidence and mortality attributable to alcohol drinking in china

Background. Cancer constitutes a serious burden of disease worldwide and has become the second leading cause of death in China. Alcohol consumption is causally associated with the increased risk of certain cancers. Due to the current lack of data and the imperative need to guide policymakers on issues of cancer prevention and control, we aim to estimate the role of alcohol on the cancer burden in China in 2005. Methods. We calculated the proportion of cancers attributable to alcohol use to estimate the burden of alcohol-related cancer. The population attributable fraction was calculated based on the assumption of no alcohol drinking. Data on alcohol drinking prevalence were from two large-scale national surveys of representative samples of the Chinese population. Data on relative risk were obtained from meta-analyses and large-scale studies. Results. We found that a total of 78,881 cancer deaths were attributable to alcohol drinking in China in 2005, representing 4.40% of all cancers (6.69% in men, 0.42% in women). The corresponding figure for cancer incidence was 93,596 cases (3.63% of all cancer cases). Liver cancer was the main alcohol-related cancer, contributing more than 60% of alcohol-related cancers. Conclusions. Particular attention needs to be paid to the harm of alcohol as well as its potential benefits when making public health recommendations on alcohol drinking. \ua9 2010 Liang et al; licensee BioMed Central Ltd

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Gold Nanoparticle Delivery of Modified CpG Stimulates Macrophages and Inhibits Tumor Growth for Enhanced Immunotherapy

Gold nanoparticle accumulation in immune cells has commonly been viewed as a side effect for cancer therapeutic delivery; however, this phenomenon can be utilized for developing gold nanoparticle mediated immunotherapy. Here, we conjugated a modified CpG oligodeoxynucleotide immune stimulant to gold nanoparticles using a simple and scalable selfassembled monolayer scheme that enhanced the functionality of CpG in vitro and in vivo. Nanoparticles can attenuate systemic side effects by enhancing CpG delivery passively to innate effector cells. The use of a triethylene glycol (TEG) spacer on top of the traditional poly-thymidine spacer increased CpG macrophage stimulatory effects without sacrificing DNA content on the nanoparticle, which directly correlates to particle uptake. In addition, the immune effects of modified CpGAuNPs were altered by the core particle size, with smaller 15 nm AuNPs generating maximum immune response. These TEG modified CpG-AuNP complexes induced macrophage and dendritic cell tumor infiltration, significantly inhibited tumor growth, and promoted survival in mice when compared to treatments with free CpG

The Role of Cilostazol, a Phosphodiesterase 3 Inhibitor, on Oocyte Maturation and Subsequent Pregnancy in Mice

It is important to identify effective contraceptive drugs that cause minimal disruption to physiological processes. Phosphodiesterase 3 (PDE3) inhibitors suppress meiosis in oocytes by decreasing the level of cAMP and blocking the extrusion of the first polar body. In this study, we tested the PDE3 inhibitor, cilostazol, as a potential contraceptive agent. The effects of cilostazol treatment in vitro and in vivo on the suppression of oocyte maturation in a mouse model were investigated. The results indicated that treatment with increasing concentrations of cilostazol led to a dose-dependent arrest in meiosis progression. The effective in vitro concentration was 1 µM and was 300 mg/kg in vivo. The effect of cilostazol was reversible. After removal of the drug, meiosis resumed and mouse oocytes matured in vitro, and showed normal chromosome alignment and spindle organization. After fertilization using an ICSI method, the oocytes showed normal morphology, fertilization rate, embryo cleavage, blastocyst formation, and number of viable pups when compared with controls. The offspring showed similar body weight and fertility. In vivo, the mice became infertile if the drug was injected sequentially, and became pregnant following discontinuation of cilostazol. More importantly, no side effects of cilostazol were observed in treated female mice as demonstrated by blood pressure and heart rate monitoring. It is concluded that cilostazol, a drug routinely used for intermittent claudication, can effectively inhibit oocyte maturation in vitro and in vivo, does not affect the developmental potential of oocytes following drug removal and has few side effects in female mice treated with this drug. These findings suggest that cilostazol may be a potential new contraceptive agent that may facilitate an efficacy and safety study of this drug

Identification and genome characterization of genotype B and genotype C bovine parainfluenza type 3 viruses isolated in the United States

BACKGROUND: Bovine parainfluenza 3 viruses (BPI3V) are respiratory pathogens of cattle that cause disease singly but are often associated with bovine respiratory disease complex (BRDC) in conjunction with other viral and bacterial agents. Bovine vaccines currently contain BPI3V to provide protection against the virus, but there is no current information regarding the BPI3V strains that are circulating in the U.S. RESULTS: A project was initiated to sequence archival BPI3V isolates to study viral evolution over time. This was done with a deep sequencing protocol that generated sequences of multiple RNA virus genomes simultaneously. Analysis of the BPI3V sequences revealed that, in addition to the genotype A (BPI3Va) viruses previously described in the United States, there were two additional genotypes of BPI3V circulating that had been described only in Australia (BPI3Vb) and Asia (BPI3Vc). The U.S. BPI3Vb and BPI3Vc isolates showed some divergence from the Australian and Asian strains; the BPI3Vb were 93 % similar to the Australian Q5592 strain and the BPI3Vc viruses were 98 % similar to the 12Q061 strain that was described in South Korea. Overall, the three genotypes were 82 to 84 % identical to each other and 80 % identical to the most similar human PI3V. Cross-neutralization studies using an APHIS/NVSL BPI3V reference serum showed that neutralization titers against the genotype B and C viruses were 4- to ≥16-fold less then the titer against the APHIS BPI3Va reference strain, SF-4. CONCLUSIONS: This study clearly demonstrated that BPI3Vb and BPI3Vc strains, previously thought to be foreign to the U.S., are indeed circulating in domestic livestock herds. Based on virus neutralization using polyclonal antisera, there were antigenic differences between viruses from these genotypes and the BPI3Va viruses that are included in currently marketed bovine vaccines. Further study of these viruses is warranted to determine pathogenic potential and cross-protection afforded by vaccination

Comparative Analysis of the Volatile Fraction of Fruit Juice from Different Citrus Species

The volatile composition of fruit from four Citrus varieties (Powell Navel orange, Clemenules mandarine, and Fortune mandarine and Chandler pummelo) covering four different species has been studied. Over one hundred compounds were profiled after HS-SPME-GC-MS analysis, including 27 esters, 23 aldehydes, 21 alcohols, 13 monoterpene hydrocarbons, 10 ketones, 5 sesquiterpene hydrocarbons, 4 monoterpene cyclic ethers, 4 furans, and 2 aromatic hydrocarbons, which were all confirmed with standards. The differences in the volatile profile among juices of these varieties were essentially quantitative and only a few compounds were found exclusively in a single variety, mainly in Chandler. The volatile profile however was able to differentiate all four varieties and revealed complex interactions between them including the participation in the same biosynthetic pathway. Some compounds (6 esters, 2 ketones, 1 furan and 2 aromatic hydrocarbons) had never been reported earlier in Citrus juices. This volatile profiling platform for Citrus juice by HS-SPME-GC-MS and the interrelationship detected among the volatiles can be used as a roadmap for future breeding or biotechnological applications

Peroxiredoxin 3 Is a Redox-Dependent Target of Thiostrepton in Malignant Mesothelioma Cells

Thiostrepton (TS) is a thiazole antibiotic that inhibits expression of FOXM1, an oncogenic transcription factor required for cell cycle progression and resistance to oncogene-induced oxidative stress. The mechanism of action of TS is unclear and strategies that enhance TS activity will improve its therapeutic potential. Analysis of human tumor specimens showed FOXM1 is broadly expressed in malignant mesothelioma (MM), an intractable tumor associated with asbestos exposure. The mechanism of action of TS was investigated in a cell culture model of human MM. As for other tumor cell types, TS inhibited expression of FOXM1 in MM cells in a dose-dependent manner. Suppression of FOXM1 expression and coincidental activation of ERK1/2 by TS were abrogated by pre-incubation of cells with the antioxidant N-acetyl-L-cysteine (NAC), indicating its mechanism of action in MM cells is redox-dependent. Examination of the mitochondrial thioredoxin reductase 2 (TR2)-thioredoxin 2 (TRX2)-peroxiredoxin 3 (PRX3) antioxidant network revealed that TS modifies the electrophoretic mobility of PRX3. Incubation of recombinant human PRX3 with TS in vitro also resulted in PRX3 with altered electrophoretic mobility. The cellular and recombinant species of modified PRX3 were resistant to dithiothreitol and SDS and suppressed by NAC, indicating that TS covalently adducts cysteine residues in PRX3. Reduction of endogenous mitochondrial TRX2 levels by the cationic triphenylmethane gentian violet (GV) promoted modification of PRX3 by TS and significantly enhanced its cytotoxic activity. Our results indicate TS covalently adducts PRX3, thereby disabling a major mitochondrial antioxidant network that counters chronic mitochondrial oxidative stress. Redox-active compounds like GV that modify the TR2/TRX2 network may significantly enhance the efficacy of TS, thereby providing a combinatorial approach for exploiting redox-dependent perturbations in mitochondrial function as a therapeutic approach in mesothelioma