Inducible nitric oxide synthase (iNOS) expression may predict distant metastasis in human melanoma

Expression of inducible nitric oxide synthase (iNOS) and its cellular localization was investigated in subcutaneous or lymph node metastases of human melanoma. Immunohistochemistry revealed that iNOS expression was limited to melanoma cells. In samples of patients without distant metastases, the number of iNOS+ tumour cells/total tumour cells was 55% ± 17% (n = 12) compared with 9% ± 8% when distant metastases of lung, liver or brain occurred within an observation period of 3 years (n = 10) (P < 0.001). Western blotting confirmed the expression of iNOS protein in select cases. Notably, iNOS is expressed in regional melanoma metastases and its expression is inversely related to the tumour's metastatic potential. Thus, iNOS expression may have predictive value for the development of distant metastases of human melanoma. © 1999 Cancer Research Campaig

Reexamination of a multisetting Bell inequality for qudits

The class of d-setting, d-outcome Bell inequalities proposed by Ji and collaborators [Phys. Rev. A 78, 052103] are reexamined. For every positive integer d > 2, we show that the corresponding non-trivial Bell inequality for probabilities provides the maximum classical winning probability of the Clauser-Horne-Shimony-Holt-like game with d inputs and d outputs. We also demonstrate that the general classical upper bounds given by Ji et al. are underestimated, which invalidates many of the corresponding correlation inequalities presented thereof. We remedy this problem, partially, by providing the actual classical upper bound for d less than or equal to 13 (including non-prime values of d). We further determine that for prime value d in this range, most of these probability and correlation inequalities are tight, i.e., facet-inducing for the respective classical correlation polytope. Stronger lower and upper bounds on the quantum violation of these inequalities are obtained. In particular, we prove that once the probability inequalities are given, their correlation counterparts given by Ji and co-workers are no longer relevant in terms of detecting the entanglement of a quantum state.Comment: v3: Published version (minor rewordings, typos corrected, upper bounds in Table III improved/corrected); v2: 7 pages, 1 figure, 4 tables (substantially revised with new results on the tightness of the correlation inequalities included); v1: 7.5 pages, 1 figure, 4 tables (Comments are welcome

A Flexible Memristor Model with Electronic Resistive Switching Memory Behavior and its Application in Spiking Neural Network

National Natural Science Foundation of China under Grant U1909201, Grant 62001149; Natural Science Foundation of Zhejiang Province under Grant LQ21F010009

Memristor-Based Hierarchical Attention Network for Multimodal Affective Computing in Mental Health Monitoring

10.13039/501100001809-National Natural Science Foundation of China (Grant Number: 62001149 and U1909201); 10.13039/501100004731-Natural Science Foundation of Zhejiang Province (Grant Number: LQ21F010009)

Shotgun proteomics: Tools for analysis of marine particulate proteins

National Natural Science Foundation of China [40821063, 40376032, 40476053]; Ministry of Science and Technology [2008DF100440]; Program for New Century Excellent Talents in Xiamen UniversityThis study sought a high resolution and high-throughput method to identify and characterize proteins from marine particulate organic matter (POM) using proteomic approaches. The results showed that only a limited number of discrete protein spots were distinguished using two-dimensional electrophoresis (2-DE). Most protein spots were faint and small in 2-DE gels, with a heavy unresolved smeared staining background, indicating 2-DE was not a good high resolution method to separate particulate proteins for identification and characterization. The shotgun proteomic approach combining one-dimensional electrophoresis and capillary liquid chromatography-tandem mass spectrometry as well as the NCBI protein database search was successfully applied to identify and characterize particulate proteins. Using this approach, 737 proteins matching one or more peptides were detected in a POM sample collected from the 41 m water layer in the basin area of the western South China Sea. Of these, 184 were identified as high-confidence proteins matching two or more peptides, including photosynthetic proteins, transporters, molecular chaperones, and porins. In addition to these proteins with known functions, a significant number of novel proteins (accounting for similar to 30% of the proteins identified) were also detected. The identification of a large number of high-confidence proteins in the POM sample demonstrated that the shotgun proteomic approach is reliable and feasible for the study of particulate proteins and will provide a powerful tool to comprehensively investigate the nature and dynamics of POM in the ocean

Phylodynamics of foot-and-mouth disease virus O/PanAsia in Vietnam 2010-2014

© 2017 The Author(s). Foot-and-mouth disease virus (FMDV) is endemic in Vietnam, a country that plays an important role in livestock trade within Southeast Asia. The large populations of FMDV-susceptible species in Vietnam are important components of food production and of the national livelihood. In this study, we investigated the phylogeny of FMDV O/PanAsia in Vietnam, reconstructing the virus' ancestral host species (pig, cattle or buffalo), clinical stage (subclinical carrier or clinically affected) and geographical location. Phylogenetic divergence time estimation and character state reconstruction analyses suggest that movement of viruses between species differ. While inferred transmissions from cattle to buffalo and pigs and from pigs to cattle are well supported, transmission from buffalo to other species, and from pigs to buffalo may be less frequent. Geographical movements of FMDV O/PanAsia virus appears to occur in all directions within the country, with the South Central Coast and the Northeast regions playing a more important role in FMDV O/PanAsia spread. Genetic selection of variants with changes at specific sites within FMDV VP1 coding region was different depending on host groups analyzed. The overall ratio of non-synonymous to synonymous nucleotide changes was greater in pigs compared to cattle and buffalo, whereas a higher number of individual amino acid sites under positive selection were detected in persistently infected, subclinical animals compared to viruses collected from clinically diseased animals. These results provide novel insights to understand FMDV evolution and its association with viral spread within endemic countries. These findings may support animal health organizations in their endeavor to design animal disease control strategies in response to outbreaks

Adiposity has differing associations with incident coronary heart disease and mortality in the Scottish population: cross-sectional surveys with follow-up

Objective: Investigation of the association of excess adiposity with three different outcomes: all-cause mortality, coronary heart disease (CHD) mortality and incident CHD. Design: Cross-sectional surveys linked to hospital admissions and death records. Subjects: 19 329 adults (aged 18–86 years) from a representative sample of the Scottish population. Measurements: Gender-stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality, CHD mortality and incident CHD. Separate models incorporating the anthropometric measurements body mass index (BMI), waist circumference (WC) or waist–hip ratio (WHR) were created adjusted for age, year of survey, smoking status and alcohol consumption. Results: For both genders, BMI-defined obesity (greater than or equal to30 kg m−2) was not associated with either an increased risk of all-cause mortality or CHD mortality. However, there was an increased risk of incident CHD among the obese men (hazard ratio (HR)=1.78; 95% confidence interval=1.37–2.31) and obese women (HR=1.93; 95% confidence interval=1.44–2.59). There was a similar pattern for WC with regard to the three outcomes; for incident CHD, the HR=1.70 (1.35–2.14) for men and 1.71 (1.28–2.29) for women in the highest WC category (men greater than or equal to102 cm, women greater than or equal to88 cm), synonymous with abdominal obesity. For men, the highest category of WHR (greater than or equal to1.0) was associated with an increased risk of all-cause mortality (1.29; 1.04–1.60) and incident CHD (1.55; 1.19–2.01). Among women with a high WHR (greater than or equal to0.85) there was an increased risk of all outcomes: all-cause mortality (1.56; 1.26–1.94), CHD mortality (2.49; 1.36–4.56) and incident CHD (1.76; 1.31–2.38). Conclusions: In this study excess adiposity was associated with an increased risk of incident CHD but not necessarily death. One possibility is that modern medical intervention has contributed to improved survival of first CHD events. The future health burden of increased obesity levels may manifest as an increase in the prevalence of individuals living with CHD and its consequences

Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe

Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery1,2, spreading efficiently via low-dose fecal-oral transmission3,4. Historically, S. sonnei has been predominantly responsible for dysentery in developed countries, but is now emerging as a problem in the developing world, apparently replacing the more diverse S. flexneri in areas undergoing economic development and improvements in water quality4-6. Classical approaches have shown S. sonnei is genetically conserved and clonal7. We report here whole-genome sequencing of 132 globally-distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and has diversified into several distinct lineages with unique characteristics. Our analysis suggests the majority of this diversification occurred in Europe, followed by more recent establishment of local pathogen populations in other continents predominantly due to the pandemic spread of a single, rapidly-evolving, multidrug resistant lineage

Onset dynamics of type A botulinum neurotoxin-induced paralysis

Experimental studies have demonstrated that botulinum neurotoxin serotype A (BoNT/A) causes flaccid paralysis by a multi-step mechanism. Following its binding to specific receptors at peripheral cholinergic nerve endings, BoNT/A is internalized by receptor-mediated endocytosis. Subsequently its zinc-dependent catalytic domain translocates into the neuroplasm where it cleaves a vesicle-docking protein, SNAP-25, to block neurally evoked cholinergic neurotransmission. We tested the hypothesis that mathematical models having a minimal number of reactions and reactants can simulate published data concerning the onset of paralysis of skeletal muscles induced by BoNT/A at the isolated rat neuromuscular junction (NMJ) and in other systems. Experimental data from several laboratories were simulated with two different models that were represented by sets of coupled, first-order differential equations. In this study, the 3-step sequential model developed by Simpson (J Pharmacol Exp Ther 212:16–21,1980) was used to estimate upper limits of the times during which anti-toxins and other impermeable inhibitors of BoNT/A can exert an effect. The experimentally determined binding reaction rate was verified to be consistent with published estimates for the rate constants for BoNT/A binding to and dissociating from its receptors. Because this 3-step model was not designed to reproduce temporal changes in paralysis with different toxin concentrations, a new BoNT/A species and rate (kS) were added at the beginning of the reaction sequence to create a 4-step scheme. This unbound initial species is transformed at a rate determined by kS to a free species that is capable of binding. By systematically adjusting the values of kS, the 4-step model simulated the rapid decline in NMJ function (kS ≥0.01), the less rapid onset of paralysis in mice following i.m. injections (kS = 0.001), and the slow onset of the therapeutic effects of BoNT/A (kS < 0.001) in man. This minimal modeling approach was not only verified by simulating experimental results, it helped to quantitatively define the time available for an inhibitor to have some effect (tinhib) and the relation between this time and the rate of paralysis onset. The 4-step model predicted that as the rate of paralysis becomes slower, the estimated upper limits of (tinhib) for impermeable inhibitors become longer. More generally, this modeling approach may be useful in studying the kinetics of other toxins or viruses that invade host cells by similar mechanisms, e.g., receptor-mediated endocytosis