The Hessian Estimation Evolution Strategy

We present a novel black box optimization algorithm called Hessian Estimation Evolution Strategy. The algorithm updates the covariance matrix of its sampling distribution by directly estimating the curvature of the objective function. This algorithm design is targeted at twice continuously differentiable problems. For this, we extend the cumulative step-size adaptation algorithm of the CMA-ES to mirrored sampling. We demonstrate that our approach to covariance matrix adaptation is efficient by evaluation it on the BBOB/COCO testbed. We also show that the algorithm is surprisingly robust when its core assumption of a twice continuously differentiable objective function is violated. The approach yields a new evolution strategy with competitive performance, and at the same time it also offers an interesting alternative to the usual covariance matrix update mechanism

Fluorescent nanoparticles for sensing

Nanoparticle-based fluorescent sensors have emerged as a competitive alternative to small molecule sensors, due to their excellent fluorescence-based sensing capabilities. The tailorability of design, architecture, and photophysical properties has attracted the attention of many research groups, resulting in numerous reports related to novel nanosensors applied in sensing a vast variety of biological analytes. Although semiconducting quantum dots have been the best-known representative of fluorescent nanoparticles for a long time, the increasing popularity of new classes of organic nanoparticle-based sensors, such as carbon dots and polymeric nanoparticles, is due to their biocompatibility, ease of synthesis, and biofunctionalization capabilities. For instance, fluorescent gold and silver nanoclusters have emerged as a less cytotoxic replacement for semiconducting quantum dot sensors. This chapter provides an overview of recent developments in nanoparticle-based sensors for chemical and biological sensing and includes a discussion on unique properties of nanoparticles of different composition, along with their basic mechanism of fluorescence, route of synthesis, and their advantages and limitations

Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders

Early-life infections and associated neuroinflammation is incriminated in the pathogenesis of various mood disorders. Infection with human roseoloviruses, HHV-6A and HHV-6B, allows viral latency in the central nervous system and other tissues, which can later be activated causing cognitive and behavioral disturbances. Hence, this study was designed to evaluate possible association of HHV-6A and HHV-6B activation with three different groups of psychiatric patients. DNA qPCR, immunofluorescence and FISH studies were carried out in post-mortem posterior cerebellum from 50 cases each of bipolar disorder (BPD), schizophrenia, 15 major depressive disorder (MDD) and 50 appropriate control samples obtained from two well-known brain collections (Stanley Medical Research Institute). HHV-6A and HHV-6B late proteins (indicating active infection) and viral DNA were detected more frequently (p < 0.001 for each virus) in human cerebellum in MDD and BPD relative to controls. These roseolovirus proteins and DNA were found less frequently in schizophrenia cases. Active HHV-6A and HHV-6B infection in cerebellar Purkinje cells were detected frequently in BPD and MDD cases. Furthermore, we found a significant association of HHV-6A infection with reduced Purkinje cell size, suggesting virus-mediated abnormal Purkinje cell function in these disorders. Finally, gene expression analysis of cerebellar tissue revealed changes in pathways reflecting an inflammatory response possibly to HHV-6A infection. Our results provide molecular evidence to support a role for active HHV-6A and HHV-6B infection in BPD and MDD

Association analysis of low-phosphorus tolerance in West African pearl millet using DArT markers

Pearl millet [Pennisetum glaucum (L.) R. Br.] is a food security crop in the harshest agricultural regions of the world. While low soil phosphorus (P) availability is a big constraint on its production, especially in West Africa (WA), information on genomic regions responsible for low-P tolerance in pearl millet is generally lacking. We present the first report on genetic polymorphisms underlying several plant P-related parameters, flowering time (FLO) and grain yield (GY) under P-limiting conditions based on 285 diversity array technology markers and 151 West African pearl millet inbred lines phenotyped in six environments in WA under both high-P and low-P conditions. Nine markers were significantly associated with P-related traits, nine markers were associated with FLO, whereas 13 markers were associated with GY each explaining between 5.5 and 15.9 % of the observed variation. Both constitutive and adaptive associations were observed for FLO and GY, with markers PgPb11603 and PgPb12954 being associated with the most stable effects on FLO and GY, respectively, across locations. There were a few shared polymorphisms between traits, especially P-efficiency-related traits and GY, implying possible colocation of genomic regions responsible for these traits. Our findings help bridge the gap between quantitative and molecular methods of studying complex traits like low-P tolerance in WA. However, validation of these markers is necessary to determine their potential applicability in marker-assisted selection programs targeting low-P environments, which are especially important in WA where resource-poor farmers are expected to be the hardest hit by the approaching global P crisis

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Characterization of single cell derived cultures of periosteal progenitor cells to ensure the cell quality for clinical application

<div><p>For clinical applications of cells and tissue engineering products it is of importance to characterize the quality of the used cells in detail. Progenitor cells from the periosteum are already routinely applied in the clinics for the regeneration of the maxillary bone. Periosteal cells have, in addition to their potential to differentiate into bone, the ability to develop into cartilage and fat. However, the question arises whether all cells isolated from periosteal biopsies are able to differentiate into all three tissue types, or whether there are subpopulations. For an efficient and approved application in bone or cartilage regeneration the clarification of this question is of interest. Therefore, 83 different clonal cultures of freshly isolated human periosteal cells derived from mastoid periosteum biopsies of 4 donors were generated and growth rates calculated. Differentiation capacities of 51 clonal cultures towards the osteogenic, the chondrogenic, and the adipogenic lineage were investigated. Histological and immunochemical stainings showed that 100% of the clonal cultures differentiated towards the osteogenic lineage, while 94.1% demonstrated chondrogenesis, and 52.9% could be stimulated to adipogenesis. For osteogenesis real-time polymerase chain reaction (PCR) of <i>BGLAP</i> and <i>RUNX2</i> and for adipogenesis of <i>FABP4</i> and <i>PPARG</i> confirmed the results. Overall, 49% of the cells exhibited a tripotent potential, 45.1% showed a bipotent potential (without adipogenic differentiation), 3.9% bipotent (without chondrogenic differentiation), and 2% possessed a unipotent osteogenic potential. In FACS analyses, no differences in the marker profile of undifferentiated clonal cultures with bi- and tripotent differentiation capacity were found. Genome-wide microarray analysis revealed 52 differentially expressed genes for clonal subpopulations with or without chondrogenic differentiation capacity, among them <i>DCN</i>, <i>NEDD9</i>, <i>TGFBR3</i>, and <i>TSLP</i>. For clinical applications of periosteal cells in bone regeneration all cells were inducible. For a chondrogenic application a fraction of 6% of the mixed population could not be induced.</p></div

Differentially expressed genes in undifferentiated clonal cultures with or without chondrogenic differentiation potential.

<p>Differentially expressed genes in undifferentiated clonal cultures with or without chondrogenic differentiation potential.</p

Histological and immunochemical stainings of osteo-, adipo- and chondrogenically induced clonal cultures.

<p>Alkaline phospahtase staining of osteogenically induced clonal cultures (A) and uninduced contols (B); Von Kossa staining of osteogenically induced clonal cultures (C) and uninduced contols (D); Oil red O staining of adipogenically inducible (E) and non-inducible (G) clonal cultures and corresponding uninduced controls (F,H); Alcian blue staining of chondrogenically inducible (I) and non-inducible (K) clonal cultures and corresponding uninduced controls (J,L); Collagen Type II immunochemical staining of chondrogenically inducible (M) and non-inducible (O) clonal cultures and corresponding uninduced controls (N,P); A-D and I-P 100x magnification, E-H 400x magnification.</p