Correspondence: No substantial long-term bias in the Cenozoic benthic foraminifera oxygen-isotope record

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Chosen-ciphertext security from subset sum

We construct a public-key encryption (PKE) scheme whose security is polynomial-time equivalent to the hardness of the Subset Sum problem. Our scheme achieves the standard notion of indistinguishability against chosen-ciphertext attacks (IND-CCA) and can be used to encrypt messages of arbitrary polynomial length, improving upon a previous construction by Lyubashevsky, Palacio, and Segev (TCC 2010) which achieved only the weaker notion of semantic security (IND-CPA) and whose concrete security decreases with the length of the message being encrypted. At the core of our construction is a trapdoor technique which originates in the work of Micciancio and Peikert (Eurocrypt 2012

The inevitable QSAR renaissance

QSAR approaches, including recent advances in 3D-QSAR, are advantageous during the lead optimization phase of drug discovery and complementary with bioinformatics and growing data accessibility. Hints for future QSAR practitioners are also offered

Characteristics of C-4 photosynthesis in stems and petioles of C-3 flowering plants

Most plants are known as C-3 plants because the first product of photosynthetic CO2 fixation is a three-carbon compound. C-4 plants, which use an alternative pathway in which the first product is a four-carbon compound, have evolved independently many times and are found in at least 18 families. In addition to differences in their biochemistry, photosynthetic organs of C-4 plants show alterations in their anatomy and ultrastructure. Little is known about whether the biochemical or anatomical characteristics of C-4 photosynthesis evolved first. Here we report that tobacco, a typical C-3 plant, shows characteristics of C-4 photosynthesis in cells of stems and petioles that surround the xylem and phloem, and that these cells are supplied with carbon for photosynthesis from the vascular system and not from stomata. These photosynthetic cells possess high activities of enzymes characteristic of C-4 photosynthesis, which allow the decarboxylation of four-carbon organic acids from the xylem and phloem, thus releasing CO2 for photosynthesis. These biochemical characteristics of C-4 photosynthesis in cells around the vascular bundles of stems of C-3 plants might explain why C-4 photosynthesis has evolved independently many times

Pharmacological therapies in post stroke recovery: Recommendations for future clinical trials

Stroke is a leading cause of serious long-term disability in adults and is the second leading cause of death worldwide. Early reperfusion and neuroprotection techniques have been the focus of much effort with the aim of very acute treatment of the stroke. Targeting different mechanisms, pharmacological therapies have the potential to reduce disability in a large fraction of patients who survive the acute stroke. The brain's capacity to reorganize after stroke through plasticity mechanisms can be modulated by pharmacological agents. A number of therapeutic interventions are under study, including small molecules, growth factors, and monoclonal antibodies. Recently it has been shown that the SSRI fluoxetine improved motor deficit in patients with ischaemic stroke and hemiplegia which appeared to be independent of the presence of depression. In this context, it is of major importance to support innovative research in order to promote the emergence of new pharmacological treatments targeting neurological recovery after stroke, as opposed to acute de-occlusion and neuroprotection. This paper is the work of a group of 14 scientists with aim of (1) addressing key areas of the basic and clinical aspects of human brain plasticity after stroke and potential pharmacological targets for recovery, (2) asking questions about the most appropriate characteristics of clinical trials testing drugs in post stroke recovery and (3) proposing recommendations for future clinical trials. © 2013 Springer-Verlag Berlin Heidelberg

Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region

Systematic assessment of training-induced changes in corticospinal output to hand using frameless stereotaxic transcranial magnetic stimulation.

Measuring changes in the characteristics of corticospinal output has become a critical part of assessing the impact of motor experience on cortical organization in both the intact and injured human brain. In this protocol we describe a method for systematically assessing training-induced changes in corticospinal output that integrates volumetric anatomical MRI with transcranial magnetic stimulation (TMS). A TMS coil is sited to a target grid superimposed onto a 3D MRI of cortex using a stereotaxic neuronavigation system. Subjects are then required to exercise the first dorsal interosseus (FDI) muscle on two different tasks for a total of 30 min. The protocol allows for reliably and repeatedly detecting changes in corticospinal output to FDI muscle in response to brief periods of motor training

Desenvolvimento de instrumento para medida dos fatores psicossociais determinantes do comportamento de atividade física em coronariopatas

Este estudo teve como objetivo apresentar o desenvolvimento, a análise de conteúdo e da confiabilidade do Questionário para identificação dos fatores psicossociais determinantes do comportamento de atividade física em coronariopatas, baseado na extensão da Teoria do Comportamento Planejado. O instrumento foi submetido à validade de conteúdo, com realização de sua avaliação por três juízes e pré-teste com cinco sujeitos, até mostrar-se conceitualmente adequado e compreensível aos sujeitos entrevistados. Foi aplicado em 51 sujeitos para a avaliação preliminar da consistência interna, por meio da determinação do coeficiente alfa de Crombach. Foram observados coeficientes alfa de Crombach >0,75 para os constructos Intenção, Atitude, Norma Subjetiva, Autoeficácia e Hábito. O instrumento desenvolvido mostrou evidências de validade de conteúdo e de confiabilidade.Este estudio tuvo como objetivo presentar el desarrollo, el análisis de contenido y de confiabilidad del Cuestionario para la identificación de los factores psicosociales determinantes del comportamiento de actividad física en pacientes afectados de coronariopatías, basado en la extensión de la Teoría del Comportamiento Planificado. Se sometió la validez del contenido del instrumento a la evaluación por parte de tres jueces y pre test con cinco sujetos, hasta mostrarse conceptualmente adecuado y comprensible para los sujetos entrevistados. Fue aplicado en 51 sujetos para la evaluación preliminar de consistencia interna, a través de la determinación del coeficiente Alfa de Cronbach. Fueron observados coeficientes Alfa de Cronbach >0,75 para los constructos Intención, Actitud, Norma Subjetiva, Autoeficacia y Hábito. El instrumento desarrollado evidenció la validez de su contenido, así como su confiabilidad.The aim of this study was to report the development and the analysis of content validity and reliability of the Psychosocial Determinants of Physical Activity among Coronary Heart Disease Patients Questionnaire, based on an extension of the Theory of Planned Behavior. In the content validity step, three experts evaluated the instrument which was, afterwards, pre-tested with five subjects in order to obtain a conceptually appropriate and easily understood instrument. Fifty-one patients participated in the evaluation of internal consistency of the reviewed instrument. Cronbach's alpha coefficients above 0.75 were observed for the constructs: Intention, Attitude, Subjective Norm, Self-efficacy and Habit. The new instrument demonstrated acceptable evidence of content validity and reliability

Genome-wide association study of Alzheimer's disease

In addition to apolipoprotein E (APOE), recent large genome-wide association studies (GWASs) have identified nine other genes/loci (CR1, BIN1, CLU, PICALM, MS4A4/MS4A6E, CD2AP, CD33, EPHA1 and ABCA7) for late-onset Alzheimer's disease (LOAD). However, the genetic effect attributable to known loci is about 50%, indicating that additional risk genes for LOAD remain to be identified. In this study, we have used a new GWAS data set from the University of Pittsburgh (1291 cases and 938 controls) to examine in detail the recently implicated nine new regions with Alzheimer's disease (AD) risk, and also performed a meta-analysis utilizing the top 1% GWAS single-nucleotide polymorphisms (SNPs) with P<0.01 along with four independent data sets (2727 cases and 3336 controls) for these SNPs in an effort to identify new AD loci. The new GWAS data were generated on the Illumina Omni1-Quad chip and imputed at ∼2.5 million markers. As expected, several markers in the APOE regions showed genome-wide significant associations in the Pittsburg sample. While we observed nominal significant associations (P<0.05) either within or adjacent to five genes (PICALM, BIN1, ABCA7, MS4A4/MS4A6E and EPHA1), significant signals were observed 69–180 kb outside of the remaining four genes (CD33, CLU, CD2AP and CR1). Meta-analysis on the top 1% SNPs revealed a suggestive novel association in the PPP1R3B gene (top SNP rs3848140 with P=3.05E–07). The association of this SNP with AD risk was consistent in all five samples with a meta-analysis odds ratio of 2.43. This is a potential candidate gene for AD as this is expressed in the brain and is involved in lipid metabolism. These findings need to be confirmed in additional samples