Saccade generation by the frontal eye fields in rhesus monkeys is separable from visual detection and bottom-up attention shift

The frontal eye fields (FEF), originally identified as an oculomotor cortex, have also been implicated in perceptual functions, such as constructing a visual saliency map and shifting visual attention. Further dissecting the area's role in the transformation from visual input to oculomotor command has been difficult because of spatial confounding between stimuli and responses and consequently between intermediate cognitive processes, such as attention shift and saccade preparation. Here we developed two tasks in which the visual stimulus and the saccade response were dissociated in space (the extended memory-guided saccade task), and bottom-up attention shift and saccade target selection were independent (the four-alternative delayed saccade task). Reversible inactivation of the FEF in rhesus monkeys disrupted, as expected, contralateral memory-guided saccades, but visual detection was demonstrated to be intact at the same field. Moreover, saccade behavior was impaired when a bottom-up shift of attention was not a prerequisite for saccade target selection, indicating that the inactivation effect was independent of the previously reported dysfunctions in bottom-up attention control. These findings underscore the motor aspect of the area's functions, especially in situations where saccades are generated by internal cognitive processes, including visual short-term memory and long-term associative memory.     

Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2

Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR)?=?1.03, 95% CI 1.00-1.06, p?=?0.023). There was evidence for heterogeneity in the ORs among studies (I(2)?=?49.3%; p?=?<0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR?=?0.89, 95%CI 0.80-1.00, p?=?0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.     

Gene selection using support vector machines with non-convex penalty

MOTIVATION: With the development of DNA microarray technology, scientists can now measure the expression levels of thousands of genes simultaneously in one single experiment. One current difficulty in interpreting microarray data comes from their innate nature of 'high-dimensional low sample size'. Therefore, robust and accurate gene selection methods are required to identify differentially expressed group of genes across different samples, e.g. between cancerous and normal cells. Successful gene selection will help to classify different cancer types, lead to a better understanding of genetic signatures in cancers and improve treatment strategies. Although gene selection and cancer classification are two closely related problems, most existing approaches handle them separately by selecting genes prior to classification. We provide a unified procedure for simultaneous gene selection and cancer classification, achieving high accuracy in both aspects. RESULTS: In this paper we develop a novel type of regularization in support vector machines (SVMs) to identify important genes for cancer classification. A special nonconvex penalty, called the smoothly clipped absolute deviation penalty, is imposed on the hinge loss function in the SVM. By systematically thresholding small estimates to zeros, the new procedure eliminates redundant genes automatically and yields a compact and accurate classifier. A successive quadratic algorithm is proposed to convert the non-differentiable and non-convex optimization problem into easily solved linear equation systems. The method is applied to two real datasets and has produced very promising results. AVAILABILITY: MATLAB codes are available upon request from the authors.     

A knee-specific finite element analysis of the human anterior cruciate ligament impingement against the femoral intercondylar notch

This work presents a finite element analysis of anterior cruciate ligament (ACL) impingement against the intercondylar notch during tibial external rotation and abduction, as a mechanism of noncontact ACL injuries. Experimentally, ACL impingement was measured in a cadaveric knee in terms of impingement contact pressure and six degrees-of-freedom tibiofemoral kinematics. Three-dimensional geometries of the ACL, femur and tibia were incorporated into the finite element model of the individual knee specimen. A fiber-reinforced model was adopted, which accounts for the anisotropy, large deformation, nonlinearity and incompressibility of the ACL. With boundary conditions specified based on the experimental tibiofemoral kinematics, the finite element analysis showed that impingement between the ligament and the lateral wall of intercondylar notch could occur when qthe knee at 45° was externally rotated at 29.1° and abducted at 10.0°. Strong contact pressure and tensile stress occurred at the impinging and nonimpinging sides of the ligament, respectively. The impingement force and contact area estimated from the model matched their counterparts from the corresponding cadaver experiment. The modeling and experimental approach provides a useful tool to characterize potential ACL impingement on a knee-specific basis, which may help elucidate the ACL injury mechanism and develop more effective treatments.     

Hydrazinocurcumin,a novel synthetic curcumin derivative,is a potent inhibitor of endothelial cell proliferation

Curcumin and some of its derivatives were known as in vivo inhibitors of angiogenesis. In present study, a novel curcumin derivative, named hydrazinocurcumin (HC) was synthesized and examined for its biological activities. HC potently inhibited the proliferation of bovine aortic endothelial cells (BAECs) at a nanomolar concentration (IC(50)=520 nM) without cytotoxicity. In vivo and in vitro angiogenesis experiments showed HC as a new candidate for anti-angiogenic agent.     

Highly stable enzyme precipitate coatings and their electrochemical applications

This paper describes highly stable enzyme precipitate coatings (EPCs) on electrospun polymer nanofibers and carbon nanotubes (CNTs), and their potential applications in the development of highly sensitive biosensors and high-powered biofuel cells. EPCs of glucose oxidase (GOx) were prepared by precipitating GOx molecules in the presence of ammonium sulfate, then cross-linking the precipitated GOx aggregates on covalently attached enzyme molecules on the surface of nanomaterials. EPCs-GOx not only improved enzyme loading, but also retained high enzyme stability. For example, EPC-GOx on CNTs showed a 50 times higher activity per unit weight of CNTs than the conventional approach of covalent attachment, and its initial activity was maintained with negligible loss for 200 days. EPC-GOx on CNTs was entrapped by Nafion to prepare enzyme electrodes for glucose sensors and biofuel cells. The EPC-GOx electrode showed a higher sensitivity and a lower detection limit than an electrode prepared with covalently attached GOx (CA-GOx). The CA-GOx electrode showed an 80% drop in sensitivity after thermal treatment at 50°C for 4 h, while the EPC-GOx electrode maintained its high sensitivity with negligible decrease under the same conditions. The use of EPC-GOx as the anode of a biofuel cell improved the power density, which was also stable even after thermal treatment of the enzyme anode at 50°C. The excellent stability of the EPC-GOx electrode together with its high current output create new potential for the practical applications of enzyme-based glucose sensors and biofuel cells.     

Single and Serial Fetal Biometry to Detect Preterm and Term Small- and Large-for-Gestational-Age Neonates: A Longitudinal Cohort Study

ObjectivesTo assess the value of single and serial fetal biometry for the prediction of small- (SGA) and large-for-gestational-age (LGA) neonates delivered preterm or at term.MethodsA cohort study of 3,971 women with singleton pregnancies was conducted from the first trimester until delivery with 3,440 pregnancies (17,334 scans) meeting the following inclusion criteria: 1) delivery of a live neonate after 33 gestational weeks and 2) two or more ultrasound examinations with fetal biometry parameters obtained at ≤36 weeks. Primary outcomes were SGA (<5^th centile) and LGA (>95^th centile) at birth based on INTERGROWTH-21^st gender-specific standards. Fetus-specific estimated fetal weight (EFW) trajectories were calculated by linear mixed-effects models using data up to a fixed gestational age (GA) cutoff (28, 32, or 36 weeks) for fetuses having two or more measurements before the GA cutoff and not already delivered. A screen test positive for single biometry was based on Z-scores of EFW at the last scan before each GA cut-off so that the false positive rate (FPR) was 10%. Similarly, a screen test positive for the longitudinal analysis was based on the projected (extrapolated) EFW at 40 weeks from all available measurements before each cutoff for each fetus.ResultsFetal abdominal and head circumference measurements, as well as birth weights in the Detroit population, matched well to the INTERGROWTH-21^st standards, yet this was not the case for biparietal diameter (BPD) and femur length (FL) (up to 9% and 10% discrepancy for mean and confidence intervals, respectively), mainly due to differences in the measurement technique. Single biometry based on EFW at the last scan at ≤32 weeks (GA IQR: 27.4–30.9 weeks) had a sensitivity of 50% and 53% (FPR = 10%) to detect preterm and term SGA and LGA neonates, respectively (AUC of 82% both). For the detection of LGA using data up to 32- and 36-week cutoffs, single biometry analysis had higher sensitivity than longitudinal analysis (52% vs 46% and 62% vs 52%, respectively; both p<0.05). Restricting the analysis to subjects with the last observation taken within two weeks from the cutoff, the sensitivity for detection of LGA, but not SGA, increased to 65% and 72% for single biometry at the 32- and 36-week cutoffs, respectively. SGA screening performance was higher for preterm (<37 weeks) than for term cases (73% vs 46% sensitivity; p<0.05) for single biometry at ≤32 weeks.ConclusionsWhen growth abnormalities are defined based on birth weight, growth velocity (captured in the longitudinal analysis) does not provide additional information when compared to the last measurement for predicting SGA and LGA neonates, with both approaches detecting one-half of the neonates (FPR = 10%) from data collected at ≤32 weeks. Unlike for SGA, LGA detection can be improved if ultrasound scans are scheduled as close as possible to the gestational-age cutoff when a decision regarding the clinical management of the patient needs to be made. Screening performance for SGA is higher for neonates that will be delivered preterm.     

P42 Ebp1 functions as a tumor suppressor in non-small cell lung cancer

Although the short isoform of ErbB3-binding protein 1 (Ebp1), p42 has been considered to be a potent tumor suppressor in a number of human cancers, whether p42 suppresses tumorigenesis of lung cancer cells has never been clarified. In the current study we investigated the tumor suppressor role of p42 in non-small cell lung cancer cells. Our data suggest that the expression level of p42 is inversely correlated with the cancerous properties of NSCLC cells and that ectopic expression of p42 is sufficient to inhibit cell proliferation, anchorage-independent growth, and invasion as well as tumor growth in vivo. Interestingly, p42 suppresses Akt activation and overexpression of a constitutively active form of Akt restores the tumorigenic activity of A549 cells that is ablated by exogenous p42 expression. Thus, we propose that p42 Ebp1 functions as a potent tumor suppressor of NSCLC through interruption of Akt signaling. [BMB Reports 2015; 48(3): 159-165]