Kinetic resolution: a powerful tool for the synthesis of planar-chiral ferrocenes

Since the serendipitous discovery of ferrocene by Pauson and Kealy in 1951, it has become one of the most important structures in Organic Chemistry. Lately, kinetic resolution has emerged as a useful tool for the synthesis of planar chiral ferrocenes. This review aims to cover and discuss the development of this topic.

Auditing the management of vaccine-preventable disease outbreaks: the need for a tool

Public health activities, especially infectious disease control, depend on effective teamwork. We present the results of a pilot audit questionnaire aimed at assessing the quality of public health services in the management of VPD outbreaks. Audit questionnaire with three main areas indicators (structure, process and results) was developed. Guidelines were set and each indicator was assessed by three auditors. Differences in indicator scores according to median size of outbreaks were determined by ANOVA (significance at p (greater than or equal to) 0.05). Of 154 outbreaks; eighteen indicators had a satisfactory mean score, indicator "updated guidelines" and "timely reporting" had a poor mean score (2.84±106 and 2.44±1.67, respectively). Statistically significant differences were found according to outbreak size, in the indicators "availability of guidelines/protocol updated less than 3 years ago" (p = 0.03) and "days needed for outbreak control" (p = 0.04). Improving availability of updated guidelines, enhancing timely reporting and adequate recording of control procedures taken is needed to allow for management assessment and improvement.

RTS,S/AS02A malaria vaccine does not induce parasite CSP T cell epitope selection and reduces multiplicity of infection

Objective: The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in children younger than age five in southern Mozambique, the vaccinedemonstrated significant and sustained efficacy against both infection and clinical disease. In a follow-up study to the main trial, breakthrough infections identified in the trial were examined to determine whether the distribution of csp sequences was affected by the vaccine and to measure the multiplicity of infecting parasite genotypes. Design: P. falciparum DNA from isolates collected during the trial was used for genotype studies. Setting: The main trial was carried out in the Manhiça district, Maputo province, Mozambique, between April 2003 and May 2004. Participants: Children from the two cohorts of the main trial provided parasite isolates as follows: children from Cohort 1 who were admitted to hospital with clinical malaria; children from Cohort 1 who were parasite-positive in a cross-sectional survey at study month 8.5; children from Cohort 2 identified as parasite-positive during follow-up by active detection of infection. Outcome: Divergence of DNA sequence encoding the CSP T cell-epitope region sequence from that of the vaccine sequence was measured in 521 isolates. The number of distinct P. falciparum genotypes was also determined. Results: We found no evidence that parasite genotypes from children in the RTS,S/AS02A arm were more divergent than those receiving control vaccines. For Cohort 1 (survey at studymonth 8.5) and Cohort 2, infections in the vaccine group contained significantly fewer genotypes than those in the control group, (p 1/4 0.035, p 1/4 0.006), respectively, for the two cohorts. This was not the case for children in Cohort 1 who were admitted to hospital (p 1/4 0.478). Conclusions: RTS,S/AS02A did not select for genotypes encoding divergent T cell epitopes in the C-terminal region of CSP in this trial. In both cohorts, there was a modest reduction in the mean number of parasite genotypes harboured by vaccinated children compared with controls, but only among those with asymptomatic infections.

Conditional manipulation of sex ratios by ant workers: A test of kin selection theory

Variable queen mating frequencies provide a unique opportunity to study the resolution of worker-queen conflict over sex ratio in social Hymenoptera, because the conflict is maximal in colonies headed by a singly mated queen and is weak or nonexistent in colonies headed by a multiply mated queen. In the wood ant Formica exsecta, workers in colonies with a singly mated queen, but not those in colonies with a multiply mated queen, altered the sex ratio of queen-laid eggs by eliminating males to preferentially raise queens. By this conditional response to queen mating frequency, workers enhance their inclusive fitness.

Community-wide plasmid gene mobilization and selection.

Plasmids have long been recognized as an important driver of DNA exchange and genetic innovation in prokaryotes. The success of plasmids has been attributed to their independent replication from the host's chromosome and their frequent self-transfer. It is thought that plasmids accumulate, rearrange and distribute nonessential genes, which may provide an advantage for host proliferation under selective conditions. In order to test this hypothesis independently of biases from culture selection, we study the plasmid metagenome from microbial communities in two activated sludge systems, one of which receives mostly household and the other chemical industry wastewater. We find that plasmids from activated sludge microbial communities carry among the largest proportion of unknown gene pools so far detected in metagenomic DNA, confirming their presumed role of DNA innovators. At a system level both plasmid metagenomes were dominated by functions associated with replication and transposition, and contained a wide variety of antibiotic and heavy metal resistances. Plasmid families were very different in the two metagenomes and grouped in deep-branching new families compared with known plasmid replicons. A number of abundant plasmid replicons could be completely assembled directly from the metagenome, providing insight in plasmid composition without culturing bias. Functionally, the two metagenomes strongly differed in several ways, including a greater abundance of genes for carbohydrate metabolism in the industrial and of general defense factors in the household activated sludge plasmid metagenome. This suggests that plasmids not only contribute to the adaptation of single individual prokaryotic species, but of the prokaryotic community as a whole under local selective conditions.

Learning wind fields with multiple kernels

This paper presents multiple kernel learning (MKL) regression as an exploratory spatial data analysis and modelling tool. The MKL approach is introduced as an extension of support vector regression, where MKL uses dedicated kernels to divide a given task into sub-problems and to treat them separately in an effective way. It provides better interpretability to non-linear robust kernel regression at the cost of a more complex numerical optimization. In particular, we investigate the use of MKL as a tool that allows us to avoid using ad-hoc topographic indices as covariables in statistical models in complex terrains. Instead, MKL learns these relationships from the data in a non-parametric fashion. A study on data simulated from real terrain features confirms the ability of MKL to enhance the interpretability of data-driven models and to aid feature selection without degrading predictive performances. Here we examine the stability of the MKL algorithm with respect to the number of training data samples and to the presence of noise. The results of a real case study are also presented, where MKL is able to exploit a large set of terrain features computed at multiple spatial scales, when predicting mean wind speed in an Alpine region.

Phytolith and spherulite studies of herbivores dung from the African Savannah as a tool for palaeocological reconstruction.

Los restos fecales están compuestos mayoritariamente por materia orgánica, la cual se degrada con el tiempo despareciendo finalmente del registro arqueológico. Sin embargo, estos restos fecales también contienen ciertos elementos resistentes al paso del tiempo y a los efectos postdeposicionales. Las esferulitas son cristales de carbonato cálcico formadas en los intestinos de ciertos animales herbívoros, principalmente rumiantes y que posteriormente son depositados en los restos fecales. Los fitolitos de sílice, aunque se forman en las plantas, son también comúnmente identificados en los restos fecales de animales herbívoros. Su número y morfología dependerá de la dieta vegetal de estos animales. El estudio que aquí se presenta se centra en el análisis microscópico de ambos elementos, fitolitos y esferulitas, identificados en restos fecales, de varios animales herbívoros, recolectados durante la estación seca en la Garganta de Olduvai en Tanzania. Los fitolitos y las esferulitas fueron identificados y analizados siguiendo un método morfológico y cuantitativo. Los fitolitos fueron luego comparados con una colección de referencia de plantas modernas de la misma zona geográfica con el propósito de estudiar la dieta de cada uno de los animales analizados. Finalmente los resultados fueron relacionados con los obtenidos del estudio de esferulitas, con el propósito de analizar la relación entre morfología y número de fitolitos y morfología y número de esferulitas para cada uno de los restos fecales analizados. El objetivo de este trabajo consiste en evaluar la utilidad de combinar ambas técnicas para identificar restos fecales en el registro arqueológico y, consecuentemente, responder a cuestiones relacionadas con el animal productor de estos restos, su dieta y movimientos migratorios y, paralelamente, la paleovegetación y el paleopaisaje en una región determinada.

Development of a GPS-Based Sign Inventory Tool for Iowa’s Statewide Management System, May 2011

This report is on state-of-the-art research efforts specific to infrastructure inventory/data collection with sign inventory as a case study. The development of an agency-wide sign inventory is based on feature inventory and location information. Specific to location, a quick and simple location acquisition tool is critical to tying assets to an accurate location-referencing system. This research effort provides a contrast between legacy referencing systems (route and milepost) and global positioning system- (GPS-) based techniques (latitude and longitude) integrated into a geographic information system (GIS) database. A summary comparison of field accuracies using a variety of consumer grade devices is also provided. This research, and the data collection tools developed, are critical in supporting the Iowa Department of Transportation (DOT) Statewide Sign Management System development effort. For the last two years, a Task Force has embarked on a comprehensive effort to develop a sign management system to improve sign quality, as well as to manage all aspects of signage, from request, ordering, fabricating, installing, maintaining, and ultimately removing, and to provide the ability to budget for these key assets on a statewide basis. This effort supported the development of a sign inventory tool and is the beginning of the development of a sign management system to support the Iowa DOT efforts in the consistent, cost effective, and objective decision making process when it comes to signs and their maintenance.

Compliance Monitoring Report Technical Assistance Tool, 2008

This form requests the minimum information required to demonstrate the extent of compliance with section 223(a)(11), 223(a)(12), 223(a)(13), 223(a)(14) of the JJDP Act of 2002. Many of these reporting requirements may be found in 28 C.F.R. 31.303(f)(5).

Compliance Monitoring Report Technical Assistance Tool, 2009

This form requests the minimum information required to demonstrate the extent of compliance with section 223(a)(11), 223(a)(12), 223(a)(13), 223(a)(14) of the JJDP Act of 2002. Many of these reporting requirements may be found in 28 C.F.R. 31.303(f)(5).

Autoimmunity-Associated LYP-W620 Does Not Impair Thymic Negative Selection of Autoreactive T Cells.

A C1858T (R620W) variation in the PTPN22 gene encoding the tyrosine phosphatase LYP is a major risk factor for human autoimmunity. LYP is a known negative regulator of signaling through the T cell receptor (TCR), and murine Ptpn22 plays a role in thymic selection. However, the mechanism of action of the R620W variant in autoimmunity remains unclear. One model holds that LYP-W620 is a gain-of-function phosphatase that causes alterations in thymic negative selection and/or thymic output of regulatory T cells (Treg) through inhibition of thymic TCR signaling. To test this model, we generated mice in which the human LYP-W620 variant or its phosphatase-inactive mutant are expressed in developing thymocytes under control of the proximal Lck promoter. We found that LYP-W620 expression results in diminished thymocyte TCR signaling, thus modeling a "gain-of-function" of LYP at the signaling level. However, LYP-W620 transgenic mice display no alterations of thymic negative selection and no anomalies in thymic output of CD4(+)Foxp3(+) Treg were detected in these mice. Lck promoter-directed expression of the human transgene also causes no alteration in thymic repertoire or increase in disease severity in a model of rheumatoid arthritis, which depends on skewed thymic selection of CD4(+) T cells. Our data suggest that a gain-of-function of LYP is unlikely to increase risk of autoimmunity through alterations of thymic selection and that LYP likely acts in the periphery perhaps selectively in regulatory T cells or in another cell type to increase risk of autoimmunity.

Multiple Kernel Learning of Environmental Data. Case study: Analysis and Mapping of Wind Fields

The paper presents the Multiple Kernel Learning (MKL) approach as a modelling and data exploratory tool and applies it to the problem of wind speed mapping. Support Vector Regression (SVR) is used to predict spatial variations of the mean wind speed from terrain features (slopes, terrain curvature, directional derivatives) generated at different spatial scales. Multiple Kernel Learning is applied to learn kernels for individual features and thematic feature subsets, both in the context of feature selection and optimal parameters determination. An empirical study on real-life data confirms the usefulness of MKL as a tool that enhances the interpretability of data-driven models.

Alkaline phosphatase activity as a tool for assessing nutritional conditions in the seagrass Posidonia oceanica.(L.) Delile

The effects of experimental phosphorus enrichments on alkaline phosphatase activity (APA) of the seagrass Posidonia oceanica (L.) Delile were tested. Short-term additions (as phosphate, 12 hours, in the laboratory) decreased APA by 18-2896, depending on the plant part considered (roots, young leaves or old leaves). The values of APA after this treatment were well correlated with interna1 phosphorus pools (as P concentration in plant tissues). Long-term additions (as phosphate, added to the sediment, 1 month in situ) decreased APA by 40-75%, also depending on the plant part. We conclude that alkaline phosphatase activity is a good indicator of P deficiency in this seagrass. We used this indicator to assess the P-nutritional status in a series of meadows in the NW Mediterranean, finding a high geographical variability, but correlations between APA and basic features of the meadows (carbonate content of the sediment, organic content of the sediment, shoot density, etc.) were not significant. Consequently, phosphorus deficiency does not seem to be directly related to these descriptors.

MBIS: multivariate Bayesian image segmentation tool.

We present MBIS (Multivariate Bayesian Image Segmentation tool), a clustering tool based on the mixture of multivariate normal distributions model. MBIS supports multichannel bias field correction based on a B-spline model. A second methodological novelty is the inclusion of graph-cuts optimization for the stationary anisotropic hidden Markov random field model. Along with MBIS, we release an evaluation framework that contains three different experiments on multi-site data. We first validate the accuracy of segmentation and the estimated bias field for each channel. MBIS outperforms a widely used segmentation tool in a cross-comparison evaluation. The second experiment demonstrates the robustness of results on atlas-free segmentation of two image sets from scan-rescan protocols on 21 healthy subjects. Multivariate segmentation is more replicable than the monospectral counterpart on T1-weighted images. Finally, we provide a third experiment to illustrate how MBIS can be used in a large-scale study of tissue volume change with increasing age in 584 healthy subjects. This last result is meaningful as multivariate segmentation performs robustly without the need for prior knowledge.