Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease

Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease. Forty-eight Parkinson’s disease patients and 39 matched healthy controls underwent genotyping and 7 T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson’s disease diagnosis. We found that, in Parkinson’s disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein(SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson’s disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson’s disease.

Application of single-cell omics in inflammatory bowel disease

Over the past decade,the advent of single cell RNA-sequencing has revolutionized the approach in cellular transcriptomics research.The current technology offers an unbiased platform to understand how genotype correlates to phenotype.Single-cell omics applications in gastrointestinal(GI)research namely inflammatory bowel disease(IBD)has become popular in the last few years with multiple publications as single-cell omics techniques can be applied directly to the target organ,the GI tract at the tissue level.Through examination of mucosal tissue and peripheral blood in IBD,the recent boom in single cell research has identified a myriad of key immune players from enterocytes to tissue resident memory T cells,and explored functional heterogeneity within cellular subsets previously unreported.As we begin to unravel the complex mucosal immune system in states of health and disease like IBD,the power of exploration through single-cell omics can change our approach to translational research.As novel techniques evolve through multiplexing single-cell omics and spatial transcriptomics come to the forefront,we can begin to fully comprehend the disease IBD and better design targets of treatment.In addition,hopefully these techniques can ultimately begin to identify biomarkers of therapeutic response and answer clinically relevant questions in how to tailor individual therapy to patients through personalized medicine.

Semiconducting SWCNT Photo Detector for High Speed Switching Through Single Halo Doping

The method opted for accuracy,and no existing studies are based on this method.A design and characteristic survey of a new small band gap semiconducting Single Wall Carbon Nano Tube(SWCNT)Field Effect Transistor as a photodetector is carried out.In the proposed device,better performance is achieved by increasing the diameter and introducing a new single halo(SH)doping in the channel length of the CNTFET device.This paper is a study and analysis of the performance of a Carbon Nano Tube Field Effect Transistor(CNTFET)as a photodetector using the self-consistent Poisson and Green function method.The 2D self-consistent Poisson and Green’s function method for various optical intensities and wavelength simulate this proposed photodetector.The performance study is based on the simulation of drain current,transconductance,sub-threshold swing,cut-off frequency,gain,directivity,and quantum efficiency under dark and illuminated conditions.These quantum simulation results show that cut-off frequency increases while there is an increase in diameter.The proposed SH-CNTFET provides better performance in terms of higher gain and directivity than conventional CNTFET(C-CNTFET).This device will be helpful in optoelectronic integrated circuits(OEIC)receivers due to its superior performance.

Three-dimensional stereotactic surface projection in the statistical analysis of single photon emission computed tomography data for distinguishing between Alzheimer's disease and depression

AIM To evaluate usefulness of single photon emission computed tomography(SPECT) with three-dimensional stereotactic surface projection(3D-SSP) in distinguishing between Alzheimer's disease(AD) and depression.METHODS We studied 43 patients who presented with both depressive symptoms and memory disturbance. Each subject was evaluated using the following:(1) the Minimal Mental State Examination;(2) the Hamilton Rating Scale for Depression;(3) Clinical Global Impression-Severity scale(CGI-S); and(4) SPECT imaging with 3D-SSP.RESULTS The MMSE scores correlated significantly with the maximum Z-scores of AD-associated regions. CGI-S scores correlated significantly with the maximum Z-scores of depression-associated regions. Factor analysis identified three significant factors. Of these, Factor 1 could be interpreted as favouring a tendency for AD, Factor 2 as favouring a tendency for pseudo-dementia, and Factor 3 as favouring a depressive tendency.CONCLUSION We investigated whether these patients could be categorized as types: Type A(true AD), Type B(pseudodementia), Type C(occult AD), and Type D(true depression). The factor scores in factor analysis supported the validity of this classification. Our results suggest that SPECT with 3D-SSP is highly useful for distinguishing between depression and depressed mood in the early stage of AD.

Semiconducting single-walled carbon nanotubes synthesized by S-doping

An approach was presented for synthesis of semiconducting single-walled carbon nanotubes(SWNTs) by sulfur(S) doping with the method of graphite arc discharge. Raman spectroscopy, UV-vis-NIR absorption spectroscopy and electronic properties measurements indicated the semconducting properties of the SWNTs samples. Simulant calculation indicated that S doping could induce convertion of metallic SWNTs into semiconducting ones. This strategy may pave a way for the direct synthesis of pure semiconducting SWNTs.

A single nucleotide polymorphism in the IL1RL1 gene is associated with Behcet's disease in a Chinese Han population

AIM:To explore the association of single nucleotide polymorphisms(SNPs)in the IL33/IL1RL1 gene region with the susceptibility to Behcet’s disease(BD)in a Chinese Han population.METHODS:A total of eight SNPs in the candidate gene region(rs11792633,rs7025417,rs10975519 and rs1048274 in IL33;rs2310220,rs12712142,rs13424006 and rs3821204 in IL1RL1)were genotyped in783 BD patients and 701 healthy controls by the Sequenom Mass Array i PLEX platform.RESULTS:A statistically significant association was observed between IL1RL1 rs12712142 and BD patients.The frequency of IL1RL1 rs12712142 variant allele A was significantly lower in BD patients than that in controls(OR=0.8,95%CI:0.69-0.94,Pc=0.039);the genotype distribution(Pc=0.043)and additive and dominant genetic model analyses(OR=0.8,95%CI:0.69-0.94,Pc=0.040 and OR=0.72,95%CI:0.58-0.88,Pc=0.011)also indicated a strong association between rs12712142 and BD patients.CONCLUSION:This is the first study to reveal the association between IL1RL1 rs12712142 variant allele A and the decreased risk of BD in the Chinese Han population,indicating a protective role of IL1RL1 in the pathogenesis of BD.

Modeling and Analysis of Single Machine Scheduling Based on Noncooperative Game Theory

Considering the independent optimization requirement for each demander of modernmanufacture, we explore the application of noncooperative game in production scheduling research,and model scheduling problem as competition of machine resources among a group of selfish jobs.Each job has its own performance objective. For the single machine, multi-jobs and non-preemptivescheduling problem, a noncooperative game model is established. Based on the model, many prob-lems about Nash equilibrium solution, such as the existence, quantity, properties of solution space,performance of solution and algorithm are discussed. The results are tested by numerical example.

MORPHOLOGY OF(Mn,Fe)S SINGLE CRYSTAL GROWTH IN CAST STEEL

The step pattern of single crystal growth and the morphology at equilibrium state of(Mn, Fe)S on the wall of micro-voids in ZG25 cast steel have been observed using scanning electron microscope.The face-centred cubic(Mn,Fe)S single crystal at equilibrium state is shown to be tetrakaidecahedron consisted of eight{111}planes and six{100}planes,and is a typical example of the O_h—m3m cubic crystal system.

A cascade of in situ conversion of bicarbonate to CO_(2) and CO_(2) electroreduction in a flow cell with a Ni-N-S catalyst

Combination of CO_(2) capture using inorganic alkali with subsequently electrochemical conversion of the resultant HCO_(3)^(-)to high-value chemicals is a promising route of low cost and high efficiency.The electrochemical reduction of HCO_(3)^(-)is challenging due to the inaccessible of negatively charged molecular groups to the electrode surface.Herein,we adopt a comprehensive strategy to tackle this challenge,i.e.,cascade of in situ chemical conversion of HCO_(3)^(-)to CO_(2) and CO_(2) electrochemical reduction in a flow cell.With a tailored Ni-N-S single atom catalyst(SACs),where sulfur(S)atoms located in the second shell of Ni center,the CO_(2)electroreduction(CO_(2)ER)to CO is boosted.The experimental results and density functional theory(DFT)calculations reveal that the introduction of S increases the p electron density of N atoms near Ni atom,thereby stabilizing^(*)H over N and boosting the first proton coupled electron transfer process of CO_(2)ER,i.e.,^(*)+e^(-)+^(*)H+^(*)CO_(2)→^(*)COOH.As a result,the obtained catalyst exhibits a high faradaic efficiency(FE_(CO)~98%)and a low overpotential of 425 mV for CO production as well as a superior turnover frequency(TOF)of 47397 h^(-1),outcompeting most of the reported Ni SACs.More importantly,an extremely high FECOof 90%is achieved at 50 mA cm^(-2)in the designed membrane electrode assembly(MEA)cascade electrolyzer fed with liquid bicarbonate.This work not only highlights the significant role of the second coordination on the first coordination shell of the central metal for CO_(2)ER,but also provides an alternative and feasible strategy to realize the electrochemical conversion of HCO_(3)^(-)to high-value chemicals.

Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease

AIM:To investigate a possible genetic influence of claudin(CLDN)1,CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS:Allelic association between genetic regions of CLDN1,CLDN2 or CLDN4 and patients with inflammatory bowel disease,Crohn's disease(CD)or ulcerative colitis were investigated using both a casecontrol study approach(one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls)and a family-based study(463 non-Swedish European inflammatory bowel disease-families).A nonsynonymous coding single nucleotide polymorphism in MORC4,located on the same linkage block as CLDN2,was investigated for association,as were two novel CLDN2 single nucleotide polymorphism markers,identified by resequencing.RESULTS:A single nucleotide polymorphism marker(rs12014762)located in the genetic region of CLDN2 was significantly associated to CD(case-control allelic OR = 1.98,95%CI:1.17-3.35,P = 0.007).MORC4 was present on the same linkage block as this CD marker.Using the case-control approach,a significant association(case control allelic OR = 1.61,95%CI:1.08-2.41,P = 0.018)was found between CD and a nonsynonymous coding single nucleotide polymorphism(rs6622126)in MORC4.The association between the CLDN2 marker and CD was not replicated in the familybased study.Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.CONCLUSION:These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.

Improved data analysis method of single-molecule experiments based on probability optimization

To extract the dynamic parameters from single molecule manipulation experiments, usually lots of data at different forces need to be recorded. But the measuring time of a single molecule is limited due to breakage of the tether or degradation of the molecule. Here we propose a data analysis method based on probability maximizalion of the recorded time trace to extract the dynamic parameters from a single measurement. The feasibility of this method was verified by dealing with the simulation data of a two-state system. We also applied this method to estimate the parameters of DNA hairpin folding and unfolding dynamics measured by a magnetic tweezers experiment.

Spectra of 42S1/2→32D5/2 Transitions of a Single Trapped 40Ca+ Ion

We investigate the spectra of the electric quadrupole 42^S1/2→3^2D5/2 transitions in a single 40^Ca＋ ion confined in a home-built linear trap. We probe the transitions with an ultra-narrow bandwidth laser at 729nm. In a weak magnetic field, the quadrupole transition splits into ten components with the maximal line strength proportional to their squared Clebsch-Gordan factors. In a magnetic field of the order of Gauss, the observed equidistant sideband reflects the Zeeman substructure modulated by the quantized oscillation due to the secular motion in the trap. The temperature of the trapped ion can be determined by the envelope of the sideband spectrum. We also demonstrate the Rabi oscillation in a carrier transition after the ion has been Doppler cooled, which can be fitted by the model with the thermal state of motion.

Genetic association analysis of CLEC5A and CLEC7A gene single-nucleotide polymorphisms and Crohn’s disease

BACKGROUND Crohn’s disease(CD)is characterized by a multifactorial etiology and a significant impact of genetic traits.While NOD2 mutations represent well established risk factors of CD,the role of other genes is incompletely understood.AIM To challenge the hypothesis that single nucleotide polymorphisms(SNPs)in the genes CLEC5 A and CLEC7 A,two members of the C-type lectin domain family of pattern recognition receptors,may be associated with CD.METHODS SNPs in CLEC5 A,CLEC7 A and the known CD risk gene NOD2 were studied using real time PCR-based SNP assays.Therefore,DNA samples from 175 patients and 157 healthy donors were employed.Genotyping data were correlated with clinical characteristics of the patients and the results of gene expression data analyses.RESULTS In accordance with previous studies,rs2066844 and rs2066847 in NOD2 were found to be significantly associated with CD(allelic P values=0.0368 and 0.0474,respectively).Intriguingly,for genotype AA of rs1285933 in CLEC5 A,a potential association with CD(recessive P=0.0523;odds ratio=1.90)was observed.There were no associations between CD and SNPs rs2078178 and rs16910631 in CLEC7 A.Variants of rs1285933 had no impact on CLEC5 A gene expression.In contrast,genotype-dependent differences of CXCL5 expression in peripheral blood mononuclear cells were observed.There is no statistical interactionbetween the tested SNPs of NOD2 and CLEC5 A,suggesting of a novel pathway contributing to the disease.CONCLUSION Our data encourage enlarged follow-up studies to further address an association of SNP rs1285933 in CLEC5 A with CD.The C-type lectin domain family member also deserves attention regarding a potential role in the pathophysiology of CD.

Intersubband transitions in Al_(0.82)In_(0.18)N/GaN single quantum well

The influence of the width of a lattice-matched A10.82In0.18N/GaN single quantum well （SQW） on the absorption coefficients and wavelength of the intersubband transition （ISBT） has been investigated by solving the Schr5dinger and Poisson equations self-consistently. The wavelength of 1-2 ISBT increases with L, the thickness of the single quantum well, ranging from 2.88 ~m to 3.59 ~.m. The absorption coefficients of 1-2 ISBT increase with L at first and then decrease with L, with a maximum when L is equal to 2.6 nm. The wavelength of 1-3 ISBT decreases with L at first and then increases with L, with a minimum when L is equal to 4 nm, ranging from approximately 2.03 p^m to near 2.11 p.m. The absorption coefficients of 1-3 ISBT decrease with L. The results indicate that mid-infrared can be realized by the A10.s2In0.1sN/GaN SQW. In addition, the wavelength and absorption coefficients of ISBT can be adjusted by changing the width of the SQW.

Deep brain stimulation of the subthalamic nucleus treats Parkinson's disease through enhancing metabolic activity of the corpus striatum Verification by single photon emission computed tomography and positron emission tomography

BACKGROUND： Subthalamic nucleus deep brain stimulation （STN DBS） for Parkinson＇s disease （PD） has achieved good effects, but to date the mechanism of STN DBS remains poorly understood STN DBS may increase dopamine levels or metabolic activity of the corpus striatum. OBJECTIVE： To validate the effects of STN DBS on dopamine metabolism and glucose metabolism in the corpus striatum of hemiparkinsonian monkeys using single photon emission computed tomography （SPECT） and position emission tomography （PET）. DESIGN, TIME AND SET＇rING： A controlled animal study was performed at the Neurosurgery Laboratory, Changhai Hospital of the Second Military Medical University of Chinese PLA between January 2004 and December 2007. METHODS： Hemiparkinsonism was induced in adult Rhesus Macaque monkeys, which exhibit similar characteristics of PD in humans, through unilateral internal carotid artery infusion of 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyrindine. Following model establishment, stimulation electrodes were implanted in the right STN, and chronic high-frequency stimulation （60 μs pulse width, 130 Hz frequency, and 1.5-2.0 V pressure） was performed. MAIN OUTCOME MEASURES： The changes in dopamine transporter （DAT）, D2 receptor （D2R）, and glucose metabolism in the corpus striatum following STN DBS were observed using SPECT and PET. RESULTS： SPECT examination showed that DAT specific binding in the right corpus striatum was increased at 3 months after DBS compared with prior to stimulation, and D2R specific binding in the right corpus striatum gradually decreased near levels on the left （non-electrode-implanted） side within 3 months after DBS. PET examination showed that the glucose metabolism in the right corpus striatum was markedly increased at 3 months after effective DBS. Hemiparkinsonism monkeys showed improved left limb rigidity, increased activities, and stable gait under chronic high-frequency stimulation. CONCLUSION： STN DBS increased striatal DAT, decreased D2R, and enhanced glucose metabolism, suggesting that chronic, high-frequency STN stimulation enhanced the metabolic activity of the corpus striatum, a mechanism for improving the PD symptoms of hemiparkinsonian monkeys.

Preparation of Single Crystals of Co_xZn_(1-x)S and Co_xZn_(1-x)Se—New Materials of Dilute Magnetic Semiconductors

In this paper, we report the growth of single crystals of Co_x Zn_(1-x)S and Co_x Zn_(1-x)Se (0<x<0.3) by the method of chemical transport, using iodine as a transport agent. The light green color of single crystal Co_xZn_(1-x)S as well as the light brown color of Co_xZn_(1-x)Se become deep with an increase in x. The compositions of the single crystals were nearly stoichiometric. The transfer rate decreases with an increase of the x value. The growth rate was related to the temperature difference. The large temperature difference speed up the growth rate, but the size of crystal obtained was small. In general, the optimal temperature difference was 15℃. From X-ray diffraction measurements, the structures of crystals Co_xZn_(1-x)S and Co_xZn_(1-x)Se (0<x<0.1) were identified to be zinc blende structure similar to that of ZnS and ZnSe.

Relationship between Sea Surface Single Carrier Waves and Decreasing Pressures of Atmosphere Lower Boundary

Descriptions of unusually high waves appearing on the sea surface for a short time (freak, rogue or killer waves) have been considered as a part of marine folklore for a long time. A number of instrumental registrations have appeared recently making the community to pay more attention to this problem and to reconsider known observations of freak waves. To allow a better understanding of the behavior of rogue waves associated with tornadoes in terms of their origin, the nonlinear theory of off-balance systems is developed in the specific case of strong agitations constantly seen on the surface of extensive and deep rivers, when they are crossed by an atmosphere’s low pressure system (tornadoes, cyclones, hurricanes, etc.). A mathematical model based on the Navier-Stokes and Euler Lagrange equations coupled with assumptions derived from instrumental registrations on the training locations (or birth places) of freak waves is developed to enhance the physics of processes responsible for the formation (or origin) of the waves associated with atmosphere’s low pressure systems. Freak waves births’ constraints are mainly the need for both consistent water (i.e., extensive-deep rivers) and potential velocity flow availabilities. Numerical simulations, based on the use of the NLSE (Nonlinear Schrodinger Equation) are performed to validate our mathematical model on the births of single carrier waves associated with atmosphere’s low pressure systems.

Fluorescence-based Multiplex PCR-Single Strand Conformation Polymorphism (SSCP) Analysis of 16S Ribosomal DNA Using Capillary Electrophoresis

The rRNA genetic locus is found in all prokaryotic organisms, and is highly conservative, although its relatively stable variations are found frequently in different bacteria. The utility of this locus as a taxonomic and phylogenetic tool has been reported widely. This study, aimed at 16S rRNA gene (16S rDNA) and with the help of biomolecular methods, attempted to achieve the goal of rapid identification of common pathogens. In this study, 333 clinical isolated pathogenic bacteria were collected. Two pairs of primers were chosen and labeled with different fluorescent dyes and then used to amplify the genomic DNA extracted from bacteria. The PCR products were then detected by capillary electrophoresis-single strand conformation polymorphism (CE-SSCP). In order to pursue higher resolution and peak-separation effect, a high efficient separating medium, liner polyacrylamidedel (LPA), was put to use in this study. Finally, every bacteria colony generated distinct patterns from each other, which were easily to be used for identification. These results indicated that PCR-CE-SSCP was a rapid identification method for bacterial identification, with the aspects of high efficiency and high precision. Compared with traditional method, this technology is of great utility for clinical use especially for its high sensitivity.

How Do Family Structure and Family Process Matter?A Comparative Study on the Impacts of Military Deployment and Single Parenthood on Children’s Psychological Well-Being

Children from two-parent families have better outcomes,on average,than children from single-parent families.Yet the mechanisms associated with family structure and family process that produce divergent outcomes are less well understood.Based on data from the 2011-2015 National Health Interview Survey(N=26,783),I leverage the case of military families with deployment and examine the impacts of parenting quality,economic capital,and social capital on children’s psychological well-being.The regression results show that single parenthood produced by divorce,separation,and birth out of wedlock leads to worse child outcomes than single parenthood produced by military deployment,and family process partially explains the variation in children’s well-being beyond family structure.Married families,military or civilian,deployed or not,enjoy advantages that translate into positive child outcomes.Marriage,therefore,emerges as the primary axis of inequality,and maintaining a healthy marriage better promotes children’s well-being.