Haplo2Ped: a tool using haplotypes as markers for linkage analysis

<p>Abstract</p> <p>Background</p> <p>Generally, SNPs are abundant in the genome; however, they display low power in linkage analysis because of their limited heterozygosity. Haplotype markers, on the other hand, which are composed of many SNPs, greatly increase heterozygosity and have superiority in linkage statistics.</p> <p>Results</p> <p>Here we developed Haplo2Ped to automatically transform SNP data into haplotype markers and then to compute the logarithm (base 10) of odds (LOD) scores of regional haplotypes that are homozygous within the disease co-segregation haploid group. The results are reported as a hypertext file and a 3D figure to help users to obtain the candidate linkage regions. The hypertext file contains parameters of the disease linked regions, candidate genes, and their links to public databases. The 3D figure clearly displays the linkage signals in each chromosome. We tested Haplo2Ped in a simulated SNP dataset and also applied it to data from a real study. It successfully and accurately located the causative genomic regions. Comparison of Haplo2Ped with other existing software for linkage analysis further indicated the high effectiveness of this software.</p> <p>Conclusions</p> <p>Haplo2Ped uses haplotype fragments as mapping markers in whole genome linkage analysis. The advantages of Haplo2Ped over other existing software include straightforward output files, increased accuracy and superior ability to deal with pedigrees showing incomplete penetrance. Haplo2Ped is freely available at: <url>http://bighapmap.big.ac.cn/software.html</url>.</p

A novel one-pot three-step synthesis of 2-(1-Benzofuran-2-yl)quinoline-3-carboxylic acid derivatives

A facile and efficient one-pot three-step procedure for the preparation of 2-(1-benzofuran-2-yl)quinoline-3-carboxylic acid derivatives is described, featuring three different synthetic transformations, namely Williamson ether synthesis, hydrolysis of an ester group at the quinoline ring C-3 position, and intramolecular electrophilic cyclization reaction between the aldehyde group of salicylaldehyde and the methylene at the quinoline ring C-2 position

Mechanical alignment tolerance of a cruciate-retaining knee prosthesis under gait loading—A finite element analysis

Component alignment is one of the most crucial factors affecting total knee arthroplasty’s clinical outcome and survival. This study aimed to investigate how coronal, sagittal, and transverse malalignment affects the mechanical behavior of the tibial insert and to determine a suitable alignment tolerance on the coronal, sagittal, and transverse planes. A finite element model of a cruciate-retaining knee prosthesis was assembled with different joint alignments (−10°, −7°, −5°, −3°, 0°, 3°, 5°, 7°, 10°) to assess the effect of malalignment under gait loading. The results showed that varus or valgus, extension, internal rotation, and excessive external rotation malalignments increased the maximum Von Mises stress and contact pressure on the tibial insert. The mechanical alignment tolerance of the studied prosthesis on the coronal, sagittal, and transverse planes was 3° varus to 3° valgus, 0°–10° flexion, and 0°–5° external rotation, respectively. This study suggests that each prosthesis should include a tolerance range for the joint alignment angle on the three planes, which may be used during surgical planning

CVD growth of large area smooth-edged graphene nanomesh by nanosphere lithography

Current etching routes to process large graphene sheets into nanoscale graphene so as to open up a bandgap tend to produce structures with rough and disordered edges. This leads to detrimental electron scattering and reduces carrier mobility. In this work, we present a novel yet simple direct-growth strategy to yield graphene nanomesh (GNM) on a patterned Cu foil via nanosphere lithography. Raman spectroscopy and TEM characterizations show that the as-grown GNM has significantly smoother edges than post-growth etched GNM. More importantly, the transistors based on as-grown GNM with neck widths of 65-75 nm have a near 3-fold higher mobility than those derived from etched GNM with the similar neck widths

Comparison of navigation systems for total knee arthroplasty: A systematic review and meta-analysis

BackgroundComponent alignment is a crucial factor affecting the clinical outcome of total knee arthroplasty (TKA). Accelerometer-based navigation (ABN) systems were developed to improve the accuracy of alignment during surgery. This study aimed to compare differences in component alignment, clinical outcomes, and surgical duration when using conventional instrumentation (CONI), ABN, and computer navigation (CN) systems.MethodsA comprehensive literature search was carried out using the Web of Science, Embase, PubMed, and Cochrane databases. Articles that met the eligibility criteria were included in the study. Meta-analyses were performed using the Cochrane Collaboration Review Manager based on Cochrane Review Method. The variables used for the analyses were postoperative clinical outcome (PCO), surgical duration, and component alignment, including the hip-knee-ankle (HKA) angle, coronal femoral angle (CFA), coronal tibial angle (CTA), sagittal femoral angle (SFA), sagittal tibial angle (STA), and the outliers for the mentioned angles. The mean difference (MD) was calculated to determine the difference between the surgical techniques for continuous variables and the odds ratio (OR) was used for the dichotomous outcomes.ResultsThe meta-analysis of the CONI and ABN system included 18 studies involving 2,070 TKA procedures, while the comparison of the ABN and CN systems included 5 studies involving 478 TKA procedures. The results showed that the ABN system provided more accurate component alignment for HKA, CFA, CTA, and SFA and produced fewer outliers for HKA, CFA, CTA, and STA. However, while the ABN system also required a significantly longer surgical time than the CONI approach, there was no statistical difference in PCO for the two systems. For the ABN and CN systems, there was no statistical difference in all variables except for the ABN system having a significantly shorter surgical duration.ConclusionThere was no significant difference in the accuracy of component alignment between the ABN and CN systems, but the ABN approach had a shorter surgical duration and at lower cost. The ABN system also significantly improved the accuracy of component alignment when compared to the CONI approach, although the surgery was longer. However, there was no significant difference in PCO between the CONI, ABN, and CN systems

High throughput Single-cell Cultivation on Microfluidic Streak Plates

This paper describes the microfluidic streak plate (MSP), a facile method for high-throughput microbial cell separation and cultivation in nanoliter sessile droplets. The MSP method builds upon the conventional streak plate technique by using microfluidic devices to generate nanoliter droplets that can be streaked manually or robotically onto petri dishes prefilled with carrier oil for cultivation of single cells. In addition, chemical gradients could be encoded in the droplet array for comprehensive dose-response analysis. The MSP method was validated by using single-cell isolation of Escherichia coli and antimicrobial susceptibility testing of Pseudomonas aeruginosa PAO1. The robustness of the MSP work flow was demonstrated by cultivating a soil community that degrades polycyclic aromatic hydrocarbons. Cultivation in droplets enabled detection of the richest species diversity with better coverage of rare species. Moreover, isolation and cultivation of bacterial strains by MSP led to the discovery of several species with high degradation efficiency, including four Mycobacterium isolates and a previously unknown fluoranthene-degrading Blastococcus species

The impact of the Wenchuan earthquake on early puberty: a natural experiment

Background The factors influencing pubertal timing have gained much attention due to a secular trend toward earlier pubertal onset in many countries. However, no studies have investigated the association between the Great earthquake and early puberty. We aimed to assess whether the Wenchuan earthquake is associated with early puberty, in both boys and girls. Methods We used data from two circles of a survey on reproductive health in China to explore the impact of the Wenchuan earthquake on early puberty , and a total of 9,785 adolescents (4,830 boys, 49.36%) aged 12–20 years from 29 schools in eight provinces were recruited. Wenchuan earthquake exposure was defined as those Sichuan students who had not experienced oigarche/menarche before May 12, 2008. Early puberty was identified as a reported onset of oigarche/menarche at 11 years or earlier. We tested the association between the Wenchuan earthquake and early puberty in boys and girls. Then, subgroup analysis stratified by the age at earthquake exposure also was performed. Results In total, 8,883 adolescents (4,543 boys, 51.14%) with a mean (SD) age of 15.13 (1.81) were included in the final sample. In general, children exposed to the earthquake had three times greater risk of early puberty (boys, RR [95% CI] = 3.18 [2.21–4.57]; girls: RR [95%CI] =3.16 [2.65–3.78]). Subgroup analysis showed that the adjusted RR was 1.90 [1.19–3.03] for boys and 2.22 [1.75–2.80] for girls. Earthquake exposure predicted almost a fourfold (RR [95%CI] = 3.91 [1.31–11.72]) increased risk of early puberty in preschool girls, whereas the increase was about twofold (RR [95%CI] = 2.09 [1.65–2.64]) in schoolgirls. Among boys, only older age at earthquake exposure was linked to early puberty (RR [95%CI] = 1.93 [1.18–3.16]). Conclusions Wenchuan earthquake exposure increased the risk of early puberty in boys and girls, and preschoolers were more at risk than schoolchildren. The implications are relevant to support policies for those survivors, especially children, to better rebuild after disasters