Gene Expression Differences in Prostate Cancers between Young and Old Men.

Prostate cancer incidence is increasing in younger men. We investigated whether men diagnosed with Gleason 7 (3+4) T2 prostate cancer at younger ages (≤ 45 years, young cohort) had different mRNA and miRNA expression profiles than men diagnosed at older ages (71-74 years, older cohort). We identified differentially expressed genes (DEGs) related to tumor-normal differences between the cohorts. Subsequent pathway analysis of DEGs revealed that the young cohort had significantly more pronounced inflammatory and immune responses to tumor development compared to the older cohort. Further supporting a role of inflammation-induced immune-suppression in the development of early-onset prostate cancer, we observed significant up-regulation of CTLA4 and IDO1/TDO2 pathways in tumors of the young cohort. Moreover, over-expression of CTLA4 and IDO1 was significantly associated with biochemical recurrence. Our results provide clues on the mechanisms of tumor development and point to potential biomarkers for early detection and treatment for prostate cancer in young men.

Influences of wing gate turnstiles' characteristics on pedestrian evacuation based on agent-based egress model.

Wing gate turnstiles are widely used in airports, subway stations, railway stations, movie theaters, parks, etc., and influence the pedestrian evacuation greatly while accidents happen. Thus, doing some researches on how to improve the evacuation speed for wing gate turnstiles are meaningful and necessary. In response to this issue, the influences of the wing gate turnstiles on pedestrian evacuation are investigated by pathfinder in this paper. Pathfinder is an agent-based egress simulator that uses steering behaviors to model occupant motion. First of all, by Pathfinder, two evacuation models with flat-shaped and wedge-shaped hosts wing gate turnstiles, respectively, are established, and the simulations of pedestrian evacuation are carried out by computer. The results show the evacuation speed obtained by the wedge-shaped host is faster than that obtained by the flat-shaped host. Moreover, the longest evacuation time is obtained when the channels' width is 90 cm, and the shortest is obtained when the channels' width is 51.4 cm. For a small number of evacuees, the evacuation time is mainly influenced by the original distributions of the evacuees, however, as the number of the evacuees increases, the evacuation time is mainly influenced by the number of the evacuees. Furthermore, the wing gate turnstiles with widened hosts can get less evacuation time no matter whether the hosts are flat-shaped or wedge-shaped, however, the evacuation-time-saved rate obtained by wedge-shaped host is much higher than that obtained by flat-shaped host. Then, the influences of the wedge angle on the pedestrian evacuation are discussed, and the optimal wedge angle is obtained. The obtained results can not only provide helps for managers to evacuate crowds under emergency, but also offer some assistances for designers to design those gate turnstiles or building exits.

Variable number tandem repeats mediate the expression of proximal genes.

Variable number tandem repeats (VNTRs) account for significant genetic variation in many organisms. In humans, VNTRs have been implicated in both Mendelian and complex disorders, but are largely ignored by genomic pipelines due to the complexity of genotyping and the computational expense. We describe adVNTR-NN, a method that uses shallow neural networks to genotype a VNTR in 18 seconds on 55X whole genome data, while maintaining high accuracy. We use adVNTR-NN to genotype 10,264 VNTRs in 652 GTEx individuals. Associating VNTR length with gene expression in 46 tissues, we identify 163 "eVNTRs". Of the 22 eVNTRs in blood where independent data is available, 21 (95%) are replicated in terms of significance and direction of association. 49% of the eVNTR loci show a strong and likely causal impact on the expression of genes and 80% have maximum effect size at least 0.3. The impacted genes are involved in diseases including Alzheimer's, obesity and familial cancers, highlighting the importance of VNTRs for understanding the genetic basis of complex diseases.

Sampled-data-based vibration control for structural systems with finite-time state constraint and sensor outage.

The problem of sampled-data-based vibration control for structural systems with finite-time state constraint and sensor outage is investigated in this paper. The objective of designing controllers is to guarantee the stability and anti-disturbance performance of the closed-loop systems while some sensor outages happen. Firstly, based on matrix transformation, the state-space model of structural systems with sensor outages and uncertainties appearing in the mass, damping and stiffness matrices is established. Secondly, by considering most of those earthquakes or strong winds happen in a very short time, and it is often the peak values make the structures damaged, the finite-time stability analysis method is introduced to constrain the state responses in a given time interval, and the H-infinity stability is adopted in the controller design to make sure that the closed-loop system has a prescribed level of disturbance attenuation performance during the whole control process. Furthermore, all stabilization conditions are expressed in the forms of linear matrix inequalities (LMIs), whose feasibility can be easily checked by using the LMI Toolbox. Finally, numerical examples are given to demonstrate the effectiveness of the proposed theorems.

Gender-specific expression of the DRD4 gene on adolescent delinquency, anger and thrill seeking.

The present study investigated gender differences in the associations between the DRD4 variable number tandem repeat (VNTR) polymorphism and adolescent delinquency, short temper and thrill seeking. We also explored whether the gender-specific expression of the DRD4 can be explained by gender differences in the exposure to psychosocial risks, such as poor parent-child relationship. Participants were 263 14- to 17-year olds (50% males) living in Russia. DNA was extracted from saliva samples and the VNTR DRD4 polymorphisms were genotyped using polymerase chain reaction. Participants reported on the extent of their delinquent behaviour, short temper, thrill seeking and exposure to psychosocial risk (i.e. poor parental monitoring of adolescent behaviour, exposure to violence and peer delinquency). Compared to individuals with the 4/4 genotype, males, but not females, with the 7-repeat allele (7R) had significantly higher delinquency, short temper and thrill seeking. This interaction effect, however, was completely explained by males' higher exposure to psychosocial risk factors. When parental monitoring of youths' activities and youth exposure to violence were included in the model, the 7R × gender interaction was no longer significant. Thus, social context plays an important role in explaining gender-specific phenotypic expression of the DRD4 gene.

Evidence of positive selection acting at the human dopamine receptor D4 gene locus.

Associations have been reported of the seven-repeat (7R) allele of the human dopamine receptor D4 (DRD4) gene with both attention-deficit/hyperactivity disorder and the personality trait of novelty seeking. This polymorphism occurs in a 48-bp tandem repeat in the coding region of DRD4, with the most common allele containing four repeats (4R) and rarer variants containing 2-11. Here we show by DNA resequencing/haplotyping of 600 DRD4 alleles, representing a worldwide population sample, that the origin of 2R-6R alleles can be explained by simple one-step recombination/mutation events. In contrast, the 7R allele is not simply related to the other common alleles, differing by greater than six recombinations/mutations. Strong linkage disequilibrium was found between the 7R allele and surrounding DRD4 polymorphisms, suggesting that this allele is at least 5-10-fold "younger" than the common 4R allele. Based on an observed bias toward nonsynonymous amino acid changes, the unusual DNA sequence organization, and the strong linkage disequilibrium surrounding the DRD4 7R allele, we propose that this allele originated as a rare mutational event that nevertheless increased to high frequency in human populations by positive selection.