Generally Covariant Actions for Multiple D-branes

We develop a formalism that allows us to write actions for multiple D-branes with manifest general covariance. While the matrix coordinates of the D-branes have a complicated transformation law under coordinate transformations, we find that these may be promoted to (redundant) matrix fields on the transverse space with a simple covariant transformation law. Using these fields, we define a covariant distribution function (a matrix generalization of the delta function which describes the location of a single brane). The final actions take the form of an integral over the curved space of a scalar single-trace action built from the covariant matrix fields, tensors involving the metric, and the covariant distribution function. For diagonal matrices, the integral localizes to the positions of the individual branes, giving N copies of the single-brane action.Comment: 34 pages, LaTeX. v2: comments and refs adde

A critical appreciation of intangible resources in PharmaNutrition

Background: Organizations in knowledge-intensive industries such as the field of PharmaNutrition benefit from a critical consideration of intangible resources for innovation performance and competitive advantage. Effective management of these resources, however, is complicated due to difficulties in their identification, appropriation, application, and evaluation. As a consequence, knowledge-intensive organizations are at risk of suboptimal exploitation of their most important value drivers. Methods: The literature on organizational intangible resources was reviewed as part of an ongoing investigation into effective management of intangible resources in the PharmaNutrition-specific context. Results: Although high-level dimensions of intangible resources are recognized across industries, the identity and relevance of various lower-level components are heterogenous and dependent on organization's unique situational attributes. Despite the existence of historical, industry-sourced tick-the-box lists presented here, an analysis of industry-specific characteristics of intangible resources and mechanisms to appropriate their value is warranted to enable practitioners to innovate effectively and efficiently. Conclusions: This editorial aims to put the topics of intangible resources and their appropriability on the agenda, and invites scholars and practitioners to contribute to the advancement of our understanding regarding these topics through an online survey

ZOBOV: a parameter-free void-finding algorithm

ZOBOV (ZOnes Bordering On Voidness) is an algorithm that finds density depressions in a set of points, without any free parameters, or assumptions about shape. It uses the Voronoi tessellation to estimate densities, which it uses to find both voids and subvoids. It also measures probabilities that each void or subvoid arises from Poisson fluctuations. This paper describes the ZOBOV algorithm, and the results from its application to the dark-matter particles in a region of the Millennium Simulation. Additionally, the paper points out an interesting high-density peak in the probability distribution of dark-matter particle densities.Comment: 10 pages, 8 figures, MNRAS, accepted. Added explanatory figures, and better edge-detection methods. ZOBOV code available at http://www.ifa.hawaii.edu/~neyrinck/vobo

Genome-wide estimation of transcript concentrations from spotted cDNA microarray data

A method providing absolute transcript concentrations from spotted microarray intensity data is presented. Number of transcripts per µg total RNA, mRNA or per cell, are obtained for each gene, enabling comparisons of transcript levels within and between tissues. The method is based on Bayesian statistical modelling incorporating available information about the experiment from target preparation to image analysis, leading to realistically large confidence intervals for estimated concentrations. The method was validated in experiments using transcripts at known concentrations, showing accuracy and reproducibility of estimated concentrations, which were also in excellent agreement with results from quantitative real-time PCR. We determined the concentration for 10 157 genes in cervix cancers and a pool of cancer cell lines and found values in the range of 10(5)–10(10) transcripts per µg total RNA. The precision of our estimates was sufficiently high to detect significant concentration differences between two tumours and between different genes within the same tumour, comparisons that are not possible with standard intensity ratios. Our method can be used to explore the regulation of pathways and to develop individualized therapies, based on absolute transcript concentrations. It can be applied broadly, facilitating the construction of the transcriptome, continuously updating it by integrating future data

A vertebra of a small species of Pachycetus from the North Sea and its inner structure and vascularity compared with other basilosaurid vertebrae from the same site

In the Western Scheldt Estuary near the Belgian-Dutch border, middle to late Eocene strata crop out at the current seafloor. Most vertebrae of large Eocene basilosaurid taxa from this area were previously described in several papers. They represent three morphotypes: elongated vertebrae of a large species of Pachycetus (Morphotype 1b), a not-elongated vertebra of a large ‘dorudontid’ basilosaurid (Morphotype 2) and ‘shortened’ vertebrae of a new, unnamed taxon (Morphotype 3). This article deals with a still undescribed, smaller vertebra, NMR-16642, from this site. Our first aim was to date it by dinoflagellate cysts in adhering sediments. Yielding an age of about 38 Ma, it is one of the very few remains of basilosaurids from Europe, of which the age could be assessed with reasonable certainty. The vertebra, Morphotype 1a, is assigned to a small species of Pachycetus. High-quality CT scans are used to differentiate between NMR-16642, Morphotype 1a, and the large species of Pachycetus, Morphotype 1b. Another aim of this paper is to investigate the inner structure and vascularity of the study vertebra and that of the other morphotypes (1b, 2, 3) from this area by using high-quality CT scans. Notwithstanding differences in size, shape and compactness, the vertebral inner structure with a multi-layered cortex of periosteal bone, surrounding two cones of endosteal bone appears to be basically similar in all morphotypes. Apparently, this inner structure reflects the ontogenetic vertebral growth. An attempt to reconstruct the vascularity of the vertebrae reveals a remarkable pattern of interconnected vascular systems. From the dorsal and, if present, ventral foramina, vascular canals are running to a central vascular node. From this node a system of vascular canals goes to the epiphyseal ends, giving rise to separate systems for cortex and cones. It is the first time that the vascularity of vertebrae of archaeocetes is investigated.</p

A vertebra of a small species of Pachycetus from the North Sea and its inner structure and vascularity compared with other basilosaurid vertebrae from the same site

In the Western Scheldt Estuary near the Belgian-Dutch border, middle to late Eocene strata crop out at the current seafloor. Most vertebrae of large Eocene basilosaurid taxa from this area were previously described in several papers. They represent three morphotypes: elongated vertebrae of a large species of Pachycetus (Morphotype 1b), a not-elongated vertebra of a large ‘dorudontid’ basilosaurid (Morphotype 2) and ‘shortened’ vertebrae of a new, unnamed taxon (Morphotype 3). This article deals with a still undescribed, smaller vertebra, NMR-16642, from this site. Our first aim was to date it by dinoflagellate cysts in adhering sediments. Yielding an age of about 38 Ma, it is one of the very few remains of basilosaurids from Europe, of which the age could be assessed with reasonable certainty. The vertebra, Morphotype 1a, is assigned to a small species of Pachycetus. High-quality CT scans are used to differentiate between NMR-16642, Morphotype 1a, and the large species of Pachycetus, Morphotype 1b. Another aim of this paper is to investigate the inner structure and vascularity of the study vertebra and that of the other morphotypes (1b, 2, 3) from this area by using high-quality CT scans. Notwithstanding differences in size, shape and compactness, the vertebral inner structure with a multi-layered cortex of periosteal bone, surrounding two cones of endosteal bone appears to be basically similar in all morphotypes. Apparently, this inner structure reflects the ontogenetic vertebral growth. An attempt to reconstruct the vascularity of the vertebrae reveals a remarkable pattern of interconnected vascular systems. From the dorsal and, if present, ventral foramina, vascular canals are running to a central vascular node. From this node a system of vascular canals goes to the epiphyseal ends, giving rise to separate systems for cortex and cones. It is the first time that the vascularity of vertebrae of archaeocetes is investigated.</p

Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis:Results from the Norfolk Arthritis Register

Objectives: Anticarbamylated protein (anti-CarP) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis. The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years’ follow-up in a cohort of patients with inflammatory polyarthritis (IP).  Methods: Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009. At baseline, Health Assessment Questionnaire (HAQ) and 28 joint disease activity scores (DAS28) were obtained, and C reactive protein, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies were measured. Further HAQ scores and DAS28 were obtained at regular intervals over 20 years. Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores; adjusting for age, gender, smoking status, year of inclusion and ACPA status. Analyses were repeated in subgroups stratified by ACPA status. The relative association of RF, ACPA and anti-CarP antibodies with HAQ and DAS28 scores was investigated using a random effects model.  Results: 1995 patients were included; 1310 (66%) were female. Anti-CarP antibodies were significantly associated with more disability and higher disease activity, HAQ multivariate β-coefficient (95% CI) 0.12 (0.02 to 0.21), and these associations remained significant in the ACPA-negative subgroups. The associations of RF, ACPA and anti-CarP antibodies were found to be additive in the random effects model.  Conclusions: Anti-CarP antibodies are associated with increased disability and higher disease activity in patients with IP. Our results suggest that measurement of anti-CarP antibodies may be useful in identifying ACPA-negative patients with worse long-term outcomes. Further, anti-CarP antibody status provided additional information about RF and ACPA

Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer : A Randomized, Double-blind, Placebo-Controlled, Phase II Study

Purpose Cachexia is a multifactorial syndrome, associated with poor survival in patients with cancer, and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer. Experimental Design: In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative gastroesophageal cancer to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics). Results: Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group (n = 12) had a higher DCR at 12 weeks (P = 0.035) compared with the autologous group (n = 12), longer median OS of 365 versus 227 days [ HR = 0.38; 95% confidence interval (CI), 0.14-1.05; P = 0.057] and PFS of 204 versus 93 days (HR = 0.50; 95% CI, 0.21-1.20; P = 0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT (P = 0.010) indicating proper engraftment of the donor microbiota. Conclusions: FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic gastroesophageal cancer. These results provide a rational for larger FMT trials.Peer reviewe

Liraglutide and sitagliptin have no effect on intestinal microbiota composition : A 12-week randomized placebo-controlled trial in adults with type 2 diabetes

Aim: Preclinical data suggest that treatment with either glucagon-like peptide (GLP)-1 receptor agonists or dipeptidyl peptidase (DPP)-4 inhibitors could change the intestinal microbiome and thereby contribute to their beneficial (cardio)metabolic effects. Therefore, our study aimed to investigate the effects of these agents on microbiota composition in adults with type 2 diabetes (T2D). Methods: A total of 51 adults with T2D (mean +/- SD: age 62.8 +/- 6.9 years, BMI 31.8 +/- 4.1 kg/m(2), HbA(1c) 7.3 +/- 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial. Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks. Faecal samples were collected at baseline and at 12 weeks after the start of the intervention. Microbiota analyses were performed by 16S rRNA gene-sequencing analysis. Bile acids were measured in faeces and plasma. Results: Liraglutide decreased HbA(1c) by 1.3% (95% CI: -1.7 to -0.9) and tended to reduce body weight (-1.7 kg, 95% CI: -3.6 to 0.3), but increased faecal secondary bile acid deoxycholic acid. Sitagliptin lowered HbA(1c) by 0.8% (95% CI: -1.4 to -0.4) while body weight remained stable (-0.8 kg, 95% CI: -2.7 to 1.0), but increased faecal levels of cholic acid, chenodeoxycholic acid and ursodeoxycholic acid. However, neither liraglutide nor sitagliptin affected either alpha or beta diversity of the intestinal microbiota, nor were changes in microbial composition related to clinical parameters. Conclusion: These data suggest that the beneficial effects of liraglutide and sitagliptin on glucose metabolism, body weight and bile acids, when used as add-on therapies to metformin or sulphonylureas, are not linked to changes in the intestinal microbiota (NCT01744236). (C) 2021 The Authors. Published by Elsevier Masson SAS.Peer reviewe