A Novel and Fast Approach for Population Structure Inference Using Kernel-PCA and Optimization

Population structure is a confounding factor in genome-wide association studies, increasing the rate of false positive associations. To correct for it, several model-based algorithms such as ADMIXTURE and STRUCTURE have been proposed. These tend to suffer from the fact that they have a considerable computational burden, limiting their applicability when used with large datasets, such as those produced by next generation sequencing techniques. To address this, nonmodel based approaches such as sparse nonnegative matrix factorization (sNMF) and EIGENSTRAT have been proposed, which scale better with larger data. Here we present a novel nonmodel-based approach, population structure inference using kernel-PCA and optimization (PSIKO), which is based on a unique combination of linear kernel-PCA and least-squares optimization and allows for the inference of admixture coefficients, principal components, and number of founder populations of a dataset. PSIKO has been compared against existing leading methods on a variety of simulation scenarios, as well as on real biological data. We found that in addition to producing results of the same quality as other tested methods, PSIKO scales extremely well with dataset size, being considerably (up to 30 times) faster for longer sequences than even state-of-the-art methods such as sNMF. PSIKO and accompanying manual are freely available at https://www.uea.ac.uk/computing/psiko.     

地塞米松联合昂丹司琼对胸腔镜术后病人静脉自控镇痛PONV的影响

目的:观察地塞米松联合昂丹司琼对胸腔镜术后病人自控静脉镇痛(PCIA)相关恶心呕吐的防治效果。方法:120例ASAⅠ~Ⅱ接受胸腔镜手术的患者,随机分为两组:地塞米松与昂丹司琼联合组(OD组)和昂丹司琼组(O组)。OD组患者在诱导时给予10 mg地塞米松,O组给予等量生理盐水,在手术结束前10分钟时,患者均给予静脉注射8 mg昂丹司琼,术后均行病人自控静脉镇痛(PCIA:生理盐水将2μg/kg舒芬太尼和8 mg昂丹司琼稀释到100 m L)。观察术后48小时内的恶心呕吐的发生率及严重程度。结果:在术后恶心呕吐整体发生率上OD组(53.3%)与O组(60%),差异无统计学意义(P0.05),但在重度PONV发生率上OD组(10%)要显著低于O组(26.7%),差异有统计学意义(P0.05)。结论:地塞米松联合昂丹司琼能有效地降低胸腔镜手术后以舒芬太尼为主的病人自控静脉镇痛所致严重恶心呕吐的发生率。     

A Novel Technique to Design and Optimize Performances of Custom Load Cells for Sport Gesture Analysis

BackgroundThe assessment of the force exerted during a gesture in human motion analysis can provide direct and indirect information regarding the expended energy, especially during the execution of a sport gesture. In this field, assessment and improvement of the performance can be supported by instrumented devices able to measure and process mechanical quantities. In cycling, strain gauges-based instrumented pedals represent one of the last innovations in the sector, because they can provide data about the power exerted (produced) during training and the pedal efficiency. Optimization of the strain-gauges positioning is thus required to improve accuracy in the exerted force estimation.MethodsA new technique to give a support for evaluating the best compromise between maximum sensitivity and ease of assembly was developed in the present work, based on a Finite Element Model (FEM) and a parametric analysis of the strain field at different sensor placements. Optimal positions were identified as those combining high sensitivity and low dependence from positioning inaccuracies.ResultsParametric strain-load trends obtained from the developed model show a linear behavior of strain gauges pairs and confirm that there is a good sensitivity of the adopted sensors if they are mounted in handy positions of the developed load cell.DiscussionThe conducted analysis enables to calculate the sensitivity of the load cell to the exerted forces, and evaluates its dependence to the positioning of strain gauges, and makes it possible to appropriately choose strain gauges positioning in areas where border effects are minimized. The strain distributions obtained by the FEM analysis in the presented load cells gives useful indications for all the situations where small strain gauges are requested to be mounted on a reduced offered area.     

格拉司琼联合隔药灸治疗肝癌介入术后恶心呕吐临床观察

目的:观察格拉司琼联合隔药灸治疗肝癌介入术后恶心呕吐临床疗效。方法:将符合纳入标准的肝癌介入术后恶心呕吐患者72例,分为治疗组与对照组,每组36例,对照组给予注射用盐酸格拉司琼静脉滴注治疗,治疗组在对照组的基础上给予隔药灸治疗。观察两组患者恶心、呕吐症状、胃液引流量及胃管留置时间,统计临床疗效。结果:治疗后治疗组在恶心、呕吐症状评分、胃液引流量、胃管留置时间方面明显均低于对照组(均P0.05)。治疗组、对照组临床疗效总有效率分别为91.67%、72.22%,比较有统计学意义(P0.05)。结论:格拉司琼联合隔药灸可以明显改善肝癌介入术后恶心呕吐症状,缩短胃管留置时间,临床疗效显著。     

发现微生物药物的新途径:从基因到新化合物

本文介绍一种基于基因组扫描(鸟枪法)和生物信息学相结合的寻找微生物新化合物的平台.基因组扫描发现新的合成基因,通过对新的次生代谢产物合成途径基因的分析,预测化合物的结构、物理化学性质参数,指导该化合物的分离与纯化.     

Bionics and Structural Biology： A Novel Approach for Bio-energy Production

Cellular metabolism is a very complex process. The biochemical pathways are fundamental structures of biology. These pathways possess a number of regeneration steps which facilitate energy shuttling on a massive scale. This facilitates the biochemical pathways to sustain the energy currency of the cells. This concept has been mimicked using electronic circuit components and it has been used to increase the efficiency of bio-energy generation. Six of the carbohydrate biochemical pathways have been chosen in which glycolysis is the principle pathway. All the six pathways are interrelated and coordinated in a complex manner. Mimic circuits have been designed for all the six biochemical pathways. The components of the metabolic pathways such as enzymes, cofactors etc., are substituted by appropriate electronic circuit components. Enzymes are related to the gain of transistors by the bond dissociation energies of enzyme-substrate molecules under consideration. Cofactors and coenzymes are represented by switches and capacitors respectively. Resistors are used for proper orientation of the circuits. The energy obtained from the current methods employed for the decomposition of organic matter is used to trigger the mimic circuits. A similar energy shuttle is observed in the mimic circuits and the percentage rise for each cycle of circuit functioning is found to be 78.90. The theoretical calculations have been made using a sample of domestic waste weighing 1.182 kg. The calculations arrived at finally speak of the efficiency of the novel methodology employed.     

Formulation and Evaluation of Fast Dissolving Films for Delivery of Triclosan to the Oral Cavity

The present investigation was undertaken with the objective of formulating TC containing fast dissolving films for local delivery to oral cavity. Various film forming agents, film modifiers and polyhydric alcohols were evaluated for optimizing the composition of fast dissolving films. The potential of poloxamer 407 and hydroxypropyl-β- cyclodextrin (HPBCD) to improve solubility of TC was investigated. Fast dissolving films containing hydroxypropyl methylcellulose (HPMC), xanthan gum, and xylitol were formulated. Use of poloxamer 407 and HPBCD resulted in significant improvement in the solubility of TC. Fast dissolving films containing TC-HPBCD complex and TC-Poloxamer 407 were formulated and were evaluated for the in vitro dissolution profile and in vitro microbiological assay. Films containing TC-Poloxamer 407 exhibited better in vitro dissolution profile and in vitro antimicrobial activity as compared to the films containing TC-HPBCD complex. Effect of incorporation of eugenol on the in vivo performance of TC-Poloxamer 407 containing films was evaluated in human volunteers. Eugenol containing films improved the acceptability of TC-Poloxamer 407 films with respect to taste masking and mouth freshening without compromising the in vivo dissolution time.     

A Method for the Investigation of Fast Water Inflow and Outflow by Changes in the External Osmotic Pressure

An original noninvasive method for monitoring water relations in plant roots is described. The gravimetric method was combined with the continuous recording of the photoelectric signal. According to this method, an intact plant was attached to the arm of a sensitive weighing beam and balanced. The root system was exposed to the air and continuously sprinkled with a solution flowing at a constant rate, in order to preserve the plant intact and to continue recording after the solution was changed. When the equilibrium was upset as a result of a change in plant weight, the movement of the beam's shutter cut off the flow of light incident on the photoelectric cell. The photocurrent was measured using a highly sensitive recording microampermeter. The method was tested with the seedlings of sunflower (Helianthus annuus L.) and tomato (Lycopersicon esculentum L.), when their roots were treated with salt solutions of various concentrations. NaCl solutions at the plasmolytic concentration induced a severe salt stress (200 mM) and brought about a significant loss of water in the plant. A similar response was observed at a lower salt concentration (10 mM) that induced neither plasmolysis nor salt stress. In both cases, the response was reversible and essentially devoid of any lag period. The method is notable for a high sensitivity (1–10 l) and a short lag time (its resolution is one second). It ensures the continuous automatic recording of even small changes in water content in intact plants. The method may be used for the investigation of immediate stress-induced water loss with an accurate estimation of short lag periods of this response.     

Quinoline-Thioureidopeptides: A New Approach for the Synthesis of Quinoline-Isothiocyanate and Their Peptide Linkage

We present an efficient synthetic route for quinoline condensed thioureidopeptidyl esters from corresponding isothiocyanate and amino acid esters. The utility of quinoline isothiocyanate as major building block for desired thioureidopeptides of quinoline interests, with good yield with excellent purity. All the new compounds are well characterized by IR, ¹H NMR, mass and elemental analysis data.     

A Novel Approach to Accounting for Loss to Follow-Up when Estimating the Relationship between CD4 Count at ART Initiation and Mortality

Background

While CD4 strongly predicts mortality on antiretroviral therapy (ART), estimates from programmatic data suffer from incomplete patient outcomes.

Methods

We conducted a pooled analysis of one-year mortality data on ART accounting for lost patients. We identified articles reporting one-year mortality by ART initiation CD4 count. We estimated the average mortality among those lost as the value that maximizes the fit of a regression of the natural log of mortality on the natural log of the imputed mean CD4 count in each band.

Results

We found 20 studies representing 64,426 subjects and 51 CD4 observations. Without correcting for losses, one-year mortality was >4.8% for all CD4 counts <200 cells/mm³. When searching over different values for mortality among those lost, the best fitting model occurs at 60% mortality. In this model, those with a CD4≤200 had a one-year mortality above 8.7, while those with a CD4>500 had a one-year mortality <6.8%. Comparing those starting ART at 500 vs. 50, one-year mortality risk was reduced by 54% (6.8 vs. 12.5%). Regardless of CD4 count, mortality was substantially higher than when assuming no mortality among those lost, ranging from a 23–94% increase.

Conclusions

Our best fitting regression estimates that every 10% increase in CD4 count at initiation is associated with a 2.8% decline in one-year mortality, including those lost. Our study supports the health benefits of higher thresholds for CD4 count initiation and suggests that reports of programmatic ART outcomes can and should adjust results for mortality among those lost.     

A Novel Approach to Enhance the Urease Activity of Sporosarcina pasteurii and its Application on Microbial-Induced Calcium Carbonate Precipitation for Sand

Abstract

Urease is involved in the formation of carbonate sediments by microbial-induced calcium carbonate precipitation (MICP), and Sporosarcina pasteurii used extensively in this technique owing to its high urease production. In this study, a simple two-step culture method with the appropriate medium was developed to enhance the urease activity of S. pasteurii. Urea played an important role in the culture process, particularly during the pre-cultivation step and the newly developed method improved both urease activity and specific urease activity. Furthermore, the increase in urease activity by MICP resulted in increased production of calcium carbonate and better strength of bio-cemented sand.     

A Comparison of Seven Fast but Approximate Methods to Compute the Free Energy of Deprotonation for Amino Acids in Aqueous Solution

Abstract

In recent years, a variety of methods based on statistical mechanics have been successfully applied to calculate free energy differences of chemical reactions from molecular simulation. The accuracy and computational efficiency vary strongly between these methods. Seven approximate but fast methods to calculate free energy differences are compared in terms of accuracy and efficiency with the accurate but expensive thermodynamic integration method as reference, using 28 protonation and deprotonation reactions of aspartic acid in aqueous solution as test cases. At least two simulations are required to obtain an accurate free energy difference between two states of the system. Both, the averaged one-step perturbation method and the linear response method yield the most accurate results, while the latter method shows the fastest convergence.     

Microfluidic Pneumatic Cages: A Novel Approach for In-chip Crystal Trapping,Manipulation and Controlled Chemical Treatment

The precise localization and controlled chemical treatment of structures on a surface are significant challenges for common laboratory technologies. Herein, we introduce a microfluidic-based technology, employing a double-layer microfluidic device, which can trap and localize in situ and ex situ synthesized structures on microfluidic channel surfaces. Crucially, we show how such a device can be used to conduct controlled chemical reactions onto on-chip trapped structures and we demonstrate how the synthetic pathway of a crystalline molecular material and its positioning inside a microfluidic channel can be precisely modified with this technology. This approach provides new opportunities for the controlled assembly of structures on surface and for their subsequent treatment.     

A Novel Statistical Approach for Jointly Analyzing RNA-Seq Data from F1 Reciprocal Crosses and Inbred Lines

RNA sequencing (RNA-seq) not only measures total gene expression but may also measure allele-specific gene expression in diploid individuals. RNA-seq data collected from F₁ reciprocal crosses in mice can powerfully dissect strain and parent-of-origin effects on allelic imbalance of gene expression. In this article, we develop a novel statistical approach to analyze RNA-seq data from F₁ and inbred strains. Method development was motivated by a study of F₁ reciprocal crosses derived from highly divergent mouse strains, to which we apply the proposed method. Our method jointly models the total number of reads and the number of allele-specific reads of each gene, which significantly boosts power for detecting strain and particularly parent-of-origin effects. The method deals with the overdispersion problem commonly observed in read counts and can flexibly adjust for the effects of covariates such as sex and read depth. The X chromosome in mouse presents particular challenges. As in other mammals, X chromosome inactivation silences one of the two X chromosomes in each female cell, although the choice of which chromosome to be silenced can be highly skewed by alleles at the X-linked X-controlling element (Xce) and stochastic effects. Our model accounts for these chromosome-wide effects on an individual level, allowing proper analysis of chromosome X expression. Furthermore, we propose a genomic control procedure to properly control type I error for RNA-seq studies. A number of these methodological improvements can also be applied to RNA-seq data from other species as well as other types of next-generation sequencing data sets. Finally, we show through simulations that increasing the number of samples is more beneficial than increasing the library size for mapping both the strain and parent-of-origin effects. Unless sample recruiting is too expensive to conduct, we recommend sequencing more samples with lower coverage.     

A Dutch Approach to the European Directive on Integrated Pollution Prevention and Control: Using Life-Cycle Assessment for the Integrated Assessment of Technologies

In light of the European Directive on Integrated Pollution Prevention and Control (IPPC Directive), traditional environmental regulation can be improved using the framework of industrial ecology. The objective of the IPPC Directive is to achieve a high level of protection of the environment as a whole (Article 1) by applying the best available techniques (BAT). In essence, the IPPC Directive obliges member states of the European Union to include considerations such as resources, energy, waste, and multimedia emissions when permitting industrial installations. This is a marked contrast to traditional environmental regulation that focuses on individual media of an individual site. In order to take all considerations into account, an integrated assessment of technologies is needed, for which a standard method is currently lacking.
In this article, a systematic approach is introduced for the integrated assessment of IPPC technologies using life-cycle assessment (LCA), a form of environmental assessment that can be broadened to an overall assessment of environmental, economic, and social aspects. This systematic approach has proven to be successful for the environmental assessment of the described cases. It is suggested here that weighting can be omitted for the evaluation of IPPC technologies. Leaving the weighting step to competent authorities of member states and allowing them to consider local issues provides maximum opportunity for the subsidiarity and flexibility principles of the IPPC Directive.     

一种用于蛋白质C端序列测定的脯氨酸乙内酰硫脲(TH-Pro)新制备方法

采用Ｌ－型脯氨酸（Ｌ－Ｐｒｏ）作为原料,三甲基硅烷异硫氰酸酯（ＴＭＳ－ＩＴＣ）作为偶联试剂制备脯氨酸乙内酰硫脲（ＴＨ－Ｐｒｏ）．产物经反相ＨＰＬＣ分离纯化,并通过氨基酸组成分析,紫外光谱扫描,质谱和核磁共振等方法鉴定．反应产率高达９６％．     

A Novel Experimental and Analytical Approach to the Multimodal Neural Decoding of Intent During Social Interaction in Freely-behaving Human Infants

Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental paradigms and analysis tools have been limited to constrained laboratory tasks and contexts due to technical limitations imposed by the available set of measuring and analysis techniques and the age of the subjects. These limitations severely limit the study of developmental neural dynamics and associated neural networks engaged in cognition, perception and action in infants performing “in action and in context”. This protocol presents a novel approach to study infants and young children as they freely organize their own behavior, and its consequences in a complex, partly unpredictable and highly dynamic environment. The proposed methodology integrates synchronized high-density active scalp electroencephalography (EEG), inertial measurement units (IMUs), video recording and behavioral analysis to capture brain activity and movement non-invasively in freely-behaving infants. This setup allows for the study of neural network dynamics in the developing brain, in action and context, as these networks are recruited during goal-oriented, exploration and social interaction tasks.     

Harnessing Senescence Delaying Gases Nitric Oxide and Nitrous Oxide: A Novel Approach to Postharvest Control of Fresh Horticultural Produce

The effects of ethylene on postharvest horticultural produce are a major limiting factor in their orderly and efficient marketing. Nitric oxide and nitrous oxide have recently been shown to inhibit ethylene action and synthesis in higher plants and their potential for commercial use to extend the storage and marketing life of fruits, vegetables and flowers is reviewed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Children at High Risk for Overweight: A Classification and Regression Trees Analysis Approach

Objective: Early identification of children at high risk for childhood overweight is a major challenge in fighting the obesity epidemic. We tried to identify the most powerful set of combined predictors for childhood overweight at school entry. Research Methods and Procedures: A classification and regression trees analysis on risk factors for childhood overweight in 4289 children 5 to 6 years of age participating in the obligatory school entry health examination 2001/2002 in Bavaria, Germany, was performed. Parental questionnaires asked for children's weight at birth and 2 years, breastfeeding history, maternal smoking in pregnancy, parental education, parental overweight/obesity, nationality, and number of older siblings. Overweight was defined according to sex‐ and age‐specific BMI cut‐points proposed by the International Obesity Task Force. Results: Prevalence of overweight was 11% among the entire study population. Although high early weight gain >10, 000 grams was found in about one‐half of the overweight children, its positive predictive value reached only 25%, indicating that one of four children with a high early weight gain is overweight at school entry. The best reliable set of predictors included high early weight gain and obese parents and accounted for a likelihood ratio of 3.6, with a corresponding positive predictive value of 40%, and was found in 4% of all children. Discussion: A combination of predictors available at 2 years of age could improve predictability of overweight at school entry. However, corresponding low positive predictive values indicate a precision of the prediction that might be insufficient for targeting intervention programs for identified high‐risk children.