Set optimization - a rather short introduction

Recent developments in set optimization are surveyed and extended including various set relations as well as fundamental constructions of a convex analysis for set- and vector-valued functions, and duality for set optimization problems. Extensive sections with bibliographical comments summarize the state of the art. Applications to vector optimization and financial risk measures are discussed along with algorithmic approaches to set optimization problems

Is annual surveillance of all treated hypothyroid patients necessary?

Peer reviewedPublisher PD

ATAQS: A computational software tool for high throughput transition optimization and validation for selected reaction monitoring mass spectrometry

<p>Abstract</p> <p>Background</p> <p>Since its inception, proteomics has essentially operated in a discovery mode with the goal of identifying and quantifying the maximal number of proteins in a sample. Increasingly, proteomic measurements are also supporting hypothesis-driven studies, in which a predetermined set of proteins is consistently detected and quantified in multiple samples. Selected reaction monitoring (SRM) is a targeted mass spectrometric technique that supports the detection and quantification of specific proteins in complex samples at high sensitivity and reproducibility. Here, we describe ATAQS, an integrated software platform that supports all stages of targeted, SRM-based proteomics experiments including target selection, transition optimization and post acquisition data analysis. This software will significantly facilitate the use of targeted proteomic techniques and contribute to the generation of highly sensitive, reproducible and complete datasets that are particularly critical for the discovery and validation of targets in hypothesis-driven studies in systems biology.</p> <p>Result</p> <p>We introduce a new open source software pipeline, ATAQS (Automated and Targeted Analysis with Quantitative SRM), which consists of a number of modules that collectively support the SRM assay development workflow for targeted proteomic experiments (project management and generation of protein, peptide and transitions and the validation of peptide detection by SRM). ATAQS provides a flexible pipeline for end-users by allowing the workflow to start or end at any point of the pipeline, and for computational biologists, by enabling the easy extension of java algorithm classes for their own algorithm plug-in or connection via an external web site.</p> <p>This integrated system supports all steps in a SRM-based experiment and provides a user-friendly GUI that can be run by any operating system that allows the installation of the Mozilla Firefox web browser.</p> <p>Conclusions</p> <p>Targeted proteomics via SRM is a powerful new technique that enables the reproducible and accurate identification and quantification of sets of proteins of interest. ATAQS is the first open-source software that supports all steps of the targeted proteomics workflow. ATAQS also provides software API (Application Program Interface) documentation that enables the addition of new algorithms to each of the workflow steps. The software, installation guide and sample dataset can be found in <url>http://tools.proteomecenter.org/ATAQS/ATAQS.html</url></p

Effects of a single administration of prostaglandin F2alpha, or a combination of prostaglandin F2alpha and prostaglandin E2, or placebo on fertility variables in dairy cows 3–5 weeks post partum, a randomized, double-blind clinical trial

BACKGROUND: Delayed uterine involution has negative effects on the fertility of cows; use of prostaglandin F2alpha alone as a single treatment has not been shown to consistently improve fertility. Combined administration of PGF2alpha and PGE2 increased uterine pressure in healthy cows. We hypothesized, that the combination of both prostaglandins would accelerate uterine involution and have, therefore, a positive effect on fertility variables. In commercial dairy farming, the benefit of a single post partum combined prostaglandin treatment should be demonstrated. METHODS: 383 cows from commercial dairy farms were included in this study. Uterine size and secretion were evaluated at treatment 21–35 days post partum and 14 days later. Cows were randomly allocated to one of three treatment groups: PGF2alpha and PGE2, PGF2alpha or placebo. For every animal participating in the study, the following reproduction variables were recorded: Interval from calving to first insemination, days open, number of artificial inseminations (AI) to conception; subsequent treatment of uterus, subsequent treatment of ovaries. Plasma progesterone level at time of treatment was used as a covariable. For continuous measurements, analysis of variance was performed. Fisher's exact test for categorical non-ordered data and exact Kruskal-Wallis test for ordered data were used; pairwise group comparisons with Bonferroni adjustment of significance level were performed. RESULTS: There was no significant difference among treatment groups in uterine size. Furthermore, there was no significant difference among treatments concerning days open, number of AI, and subsequent treatment of uterus and ovaries. Days from calving to first insemination tended to be shorter for cows with low progesterone level given PGF2alpha and PGE2 in combination than for the placebo-group (P = 0.024). CONCLUSION: The results of this study indicate that the administration of PGF2alpha or a combination of PGF2alpha and PGE2 21 to 35 days post partum had no beneficial effect upon measured fertility variables. The exception was a tendency for a shorter interval from calving to first insemination after administration of the combination of PGF2alpha and PGE2, as compared to the placebo group. Further research should be done in herds with reduced fertility and/or an increased incidence of postpartum vaginal discharge

DNA Clasping by Mycobacterial HU: The C-Terminal Region of HupB Mediates Increased Specificity of DNA Binding

BACKGROUND: HU a small, basic, histone like protein is a major component of the bacterial nucleoid. E. coli has two subunits of HU coded by hupA and hupB genes whereas Mycobacterium tuberculosis (Mtb) has only one subunit of HU coded by ORF Rv2986c (hupB gene). One noticeable feature regarding Mtb HupB, based on sequence alignment of HU orthologs from different bacteria, was that HupB(Mtb) bears at its C-terminal end, a highly basic extension and this prompted an examination of its role in Mtb HupB function. METHODOLOGY/PRINCIPAL FINDINGS: With this objective two clones of Mtb HupB were generated; one expressing full length HupB protein (HupB(Mtb)) and another which expresses only the N terminal region (first 95 amino acid) of hupB (HupB(MtbN)). Gel retardation assays revealed that HupB(MtbN) is almost like E. coli HU (heat stable nucleoid protein) in terms of its DNA binding, with a binding constant (K(d)) for linear dsDNA greater than 1000 nM, a value comparable to that obtained for the HUalphaalpha and HUalphabeta forms. However CTR (C-terminal Region) of HupB(Mtb) imparts greater specificity in DNA binding. HupB(Mtb) protein binds more strongly to supercoiled plasmid DNA than to linear DNA, also this binding is very stable as it provides DNase I protection even up to 5 minutes. Similar results were obtained when the abilities of both proteins to mediate protection against DNA strand cleavage by hydroxyl radicals generated by the Fenton's reaction, were compared. It was also observed that both the proteins have DNA binding preference for A:T rich DNA which may occur at the regulatory regions of ORFs and the oriC region of Mtb. CONCLUSIONS/SIGNIFICANCE: These data thus point that HupB(Mtb) may participate in chromosome organization in-vivo, it may also play a passive, possibly an architectural role

Genetic variation and diversity of pearl millet [Pennisetum glaucum (L.)] genotypes assessed for millet head miner, Heliocheilus albipunctella resistance, in West Africa

Pearl millet (Pennisetum glaucum L.), the major source of minerals and dietary energy for people living in the semi-arid regions of Sahel, is regularly damaged by millet head miner, Heliocheilus albipunctella. In order to identify the plant-based resistance sources for millet head miner along with high grain Fe and Zn, we have screened forty pearl millet genotypes, using an artificial infestation method. Analysis of variance revealed significant differences in the genotypes tested for head miner resistance. The genotypes Gamoji, ICMP 177001, ICMP 177002, ICMV 177003, ICMV IS 90311, LCIC9702, Souna 3, ICMV IS 94206 and PE08043 exhibited antibiosis resistance mechanism to Heliocheilus albipunctella with appreciable agronomy and grain yield when compared with the susceptible check ICMV IS 92222. The genotypes Faringuero, ICMV 167005, ICMV IS 99001, Sadore local, SOSAT-C88, and ICMP 177004 exhibited tolerance to head miner damage with good per se performance. The genotypes ICMP 177001, ICMP 177002, ICMV 177003, and Moro exhibited resistance to millet head miner and had consistent grain Fe content across seasons (ranging from 44 to 70 ppm). Association between the head miner resistance and morphological traits showed a positive and significant correlation of larval production index (%) with head miner damage (r = 0.59**). Grain Fe and Zn contents exhibited negative association with panicle length and grain yield indicating proper care should be taken in breeding for these traits. Hence, the identified resistance sources can be effectively utilized in breeding head miner resistant pearl millet OPV’s/ hybrids, with high grain yield including Fe and Zn concentrations, to overcome the hunger and malnutrition seen in populations living in the semi-arid tropics

Rpb1 Sumoylation in Response to UV Radiation or Transcriptional Impairment in Yeast

Covalent modifications of proteins by ubiquitin and the Small Ubiquitin-like MOdifier (SUMO) have been revealed to be involved in a plethora of cellular processes, including transcription, DNA repair and DNA damage responses. It has been well known that in response to DNA damage that blocks transcription elongation, Rpb1, the largest subunit of RNA polymerase II (Pol II), is ubiquitylated and subsequently degraded in mammalian and yeast cells. However, it is still an enigma regarding how Pol II responds to damaged DNA and conveys signal(s) for DNA damage-related cellular processes. We found that Rpb1 is also sumoylated in yeast cells upon UV radiation or impairment of transcription elongation, and this modification is independent of DNA damage checkpoint activation. Ubc9, an E2 SUMO conjugase, and Siz1, an E3 SUMO ligase, play important roles in Rpb1 sumoylation. K1487, which is located in the acidic linker region between the C-terminal domain and the globular domain of Rpb1, is the major sumoylation site. Rpb1 sumoylation is not affected by its ubiquitylation, and vice versa, indicating that the two processes do not crosstalk. Abolishment of Rpb1 sumoylation at K1487 does not affect transcription elongation or transcription coupled repair (TCR) of UV-induced DNA damage. However, deficiency in TCR enhances UV-induced Rpb1 sumoylation, presumably due to the persistence of transcription-blocking DNA lesions in the transcribed strand of a gene. Remarkably, abolishment of Rpb1 sumoylation at K1487 causes enhanced and prolonged UV-induced phosphorylation of Rad53, especially in TCR-deficient cells, suggesting that the sumoylation plays a role in restraining the DNA damage checkpoint response caused by transcription-blocking lesions. Our results demonstrate a novel covalent modification of Rpb1 in response to UV induced DNA damage or transcriptional impairment, and unravel an important link between the modification and the DNA damage checkpoint response

Collaborative development of predictive toxicology applications

OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative) Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling. OpenTox provides end-user oriented tools to non-computational specialists, risk assessors, and toxicological experts in addition to Application Programming Interfaces (APIs) for developers of new applications. OpenTox actively supports public standards for data representation, interfaces, vocabularies and ontologies, Open Source approaches to core platform components, and community-based collaboration approaches, so as to progress system interoperability goals

Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life.

BACKGROUND: Factors driving inter-individual differences in immune responses upon different types of prenatal malaria exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate immune responses modulate the risk of malaria during the first year of life. METHODS: We conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial (NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations and ratios of TLR-mediated cytokine responses relative to background control were analyzed. RESULTS: Spontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group. However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life. CONCLUSIONS: These findings indicate that past placental malaria has a profound effect on fetal immune system and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life