Integral geometry of complex space forms

We show how Alesker's theory of valuations on manifolds gives rise to an algebraic picture of the integral geometry of any Riemannian isotropic space. We then apply this method to give a thorough account of the integral geometry of the complex space forms, i.e. complex projective space, complex hyperbolic space and complex euclidean space. In particular, we compute the family of kinematic formulas for invariant valuations and invariant curvature measures in these spaces. In addition to new and more efficient framings of the tube formulas of Gray and the kinematic formulas of Shifrin, this approach yields a new formula expressing the volumes of the tubes about a totally real submanifold in terms of its intrinsic Riemannian structure. We also show by direct calculation that the Lipschitz-Killing valuations stabilize the subspace of invariant angular curvature measures, suggesting the possibility that a similar phenomenon holds for all Riemannian manifolds. We conclude with a number of open questions and conjectures.Comment: 68 pages; minor change

On the total curvatures of a tame function

Given a definable function f, enough differentiable, we study the continuity of the total curvature function t --> K(t), total curvature of the level {f=t}, and the total absolute curvature function t-->|K| (t), total absolute curvature of the level {f=t}. We show they admits at most finitely many discontinuities

MBL2 and Hepatitis C Virus Infection among Injection Drug Users

<p>Abstract</p> <p>Background</p> <p>Genetic variations in <it>MBL2 </it>that reduce circulating levels and alter functional properties of the mannose binding lectin (MBL) have been associated with many autoimmune and infectious diseases. We examined whether <it>MBL2 </it>variants influence the outcome of hepatitis C virus (HCV) infection.</p> <p>Methods</p> <p>Participants were enrolled in the Urban Health Study of San Francisco Bay area injection drug users (IDU) during 1998 through 2000. Study subjects who had a positive test for HCV antibody were eligible for the current study. Participants who were positive for HCV RNA were frequency matched to those who were negative for HCV RNA on the basis of ethnicity and duration of IDU. Genotyping was performed for 15 single nucleotide polymorphisms in <it>MBL2</it>. Statistical analyses of European American and African American participants were conducted separately.</p> <p>Results</p> <p>The analysis included 198 study subjects who were positive for HCV antibody, but negative for HCV RNA, and 654 IDUs who were positive for both antibody and virus. There was no significant association between any of the genetic variants that cause MBL deficiency and the presence of HCV RNA. Unexpectedly, the <it>MBL2 </it>-289X promoter genotype, which causes MBL deficiency, was over-represented among European Americans who were HCV RNA negative (OR = 1.65, 95% CI 1.05–2.58), although not among the African Americans.</p> <p>Conclusion</p> <p>This study found no association between genetic variants that cause MBL deficiency and the presence of HCV RNA. The observation that <it>MBL2 </it>-289X was associated with the absence of HCV RNA in European Americans requires validation.</p

Proteomics analysis of serum protein profiling in pancreatic cancer patients by DIGE: up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer has significant morbidity and mortality worldwide. Good prognosis relies on an early diagnosis. The purpose of this study was to develop techniques for identifying cancer biomarkers in the serum of patients with pancreatic cancer.</p> <p>Methods</p> <p>Serum samples from five individuals with pancreatic cancer and five individuals without cancer were compared. Highly abundant serum proteins were depleted by immuno-affinity column. Differential protein analysis was performed using 2-dimensional differential in-gel electrophoresis (2D-DIGE).</p> <p>Results</p> <p>Among these protein spots, we found that 16 protein spots were differently expressed between the two mixtures; 8 of these were up-regulated and 8 were down-regulated in cancer. Mass spectrometry and database searching allowed the identification of the proteins corresponding to the gel spots. Up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2, which have not previously been implicated in pancreatic cancer, were observed. In an independent series of serum samples from 16 patients with pancreatic cancer and 16 non-cancer-bearing controls, increased levels of mannose-binding lectin 2 and myosin light chain kinase 2 were confirmed by western blot.</p> <p>Conclusions</p> <p>These results suggest that affinity column enrichment and DIGE can be used to identify proteins differentially expressed in serum from pancreatic cancer patients. These two proteins 'mannose-binding lectin 2 and myosin light chain kinase 2' might be potential biomarkers for the diagnosis of the pancreatic cancer.</p

Variant G57E of Mannose Binding Lectin Associated with Protection against Tuberculosis Caused by Mycobacterium africanum but not by M. tuberculosis

Structural variants of the Mannose Binding Lectin (MBL) cause quantitative and qualitative functional deficiencies, which are associated with various patterns of susceptibility to infectious diseases and other disorders. We determined genetic MBL variants in 2010 Ghanaian patients with pulmonary tuberculosis (TB) and 2346 controls and characterized the mycobacterial isolates of the patients. Assuming a recessive mode of inheritance, we found a protective association between TB and the MBL2 G57E variant (odds ratio 0.60, confidence interval 0.4–0.9, P 0.008) and the corresponding LYQC haplotype (Pcorrected 0.007) which applied, however, only to TB caused by M. africanum but not to TB caused by M. tuberculosis. In vitro, M. africanum isolates bound recombinant human MBL more efficiently than did isolates of M. tuberculosis. We conclude that MBL binding may facilitate the uptake of M. africanum by macrophages, thereby promoting infection and that selection by TB may have favoured the spread of functional MBL deficiencies in regions endemic for M. africanum

Area minimizing discs in metric spaces

We solve the classical problem of Plateau in the setting of proper metric spaces. Precisely, we prove that among all disc-type surfaces with prescribed Jordan boundary in a proper metric space there exists an area minimizing disc which moreover has a quasi-conformal parametrization. If the space supports a local quadratic isoperimetric inequality for curves we prove that such a solution is locally Hölder continuous in the interior and continuous up to the boundary. Our results generalize corresponding results of Douglas Radò and Morrey from the setting of Euclidean space and Riemannian manifolds to that of proper metric spaces

Intriguing Balancing Selection on the Intron 5 Region of LMBR1 in Human Population

Background: The intron 5 of gene LMBR1 is the cis-acting regulatory module for the sonic hedgehog (SHH) gene. Mutation in this non-coding region is associated with preaxial polydactyly, and may play crucial roles in the evolution of limb and skeletal system. Methodology/Principal Findings: We sequenced a region of the LMBR1 gene intron 5 in East Asian human population, and found a significant deviation of Tajima’s D statistics from neutrality taking human population growth into account. Data from HapMap also demonstrated extended linkage disequilibrium in the region in East Asian and European population, and significantly low degree of genetic differentiation among human populations. Conclusion/Significance: We proposed that the intron 5 of LMBR1 was presumably subject to balancing selection during the evolution of modern human

Mannose-Binding Lectin 2 Polymorphisms Do Not Influence Frequency or Type of Infection in Adults with Chemotherapy Induced Neutropaenia

BACKGROUND: Mannose-binding Lectin protein (MBL) has been suggested to be relevant in the defence against infections in immunosuppressed individuals. In a Swedish adult cohort immunosuppressed from both the underlying disease and from iatrogenic treatments for their underlying disease we investigated the role of MBL in susceptibility to infection. METHODS: In this cross sectional, prospective study, blood samples obtained from 96 neutropaenic febrile episodes, representing 82 individuals were analysed for single nucleotide polymorphism (SNP) in the MBL2 gene. Concurrent measurement of plasma MBL protein concentrations was also performed for observation of acute response during febrile episodes. FINDINGS: No association was observed between MBL2 genotype or plasma MBL concentrations, and the type or frequency of infection. Adding to the literature, we found no evidence that viral infections or co-infections with virus and bacteria would be predisposed by MBL deficiency. We further saw no correlation between MBL2 genotype and the risk of fever. However, fever duration in febrile neutropaenic episodes was negatively associated with MBL2 SNP mutations (p<0.05). Patients with MBL2 SNP mutations presented a median febrile duration of 1.8 days compared with 3 days amongst patients with wildtype MBL2 genotype. INTERPRETATION: We found no clear association between infection, or infection type to MBL2 genotypes or plasma MBL concentration, and add to the reports casting doubts on the benefit of recombinant MBL replacement therapy use during iatrogenic neutropaenia

Genetic and other factors determining mannose-binding lectin levels in American Indians: the Strong Heart Study

<p>Abstract</p> <p>Background</p> <p>Mannose-binding lectin (MBL) forms an integral part of the innate immune system. Persistent, subclinical infections and chronic inflammatory states are hypothesized to contribute to the pathogenesis of atherosclerosis. MBL gene (<it>MBL2</it>) variants with between 12 to 25% allele frequency in Caucasian and other populations, result in markedly reduced expression of functional protein. Prospective epidemiologic studies, including a nested, case-control study from the present population, have demonstrated the ability of <it>MBL2 </it>genotypes to predict complications of atherosclerosis,. The genetic control of <it>MBL2 </it>expression is complex and genetic background effects in specific populations are largely unknown.</p> <p>Methods</p> <p>The Strong Heart Study is a longitudinal, cohort study of cardiovascular disease among American Indians. A subset of individuals genotyped for the above mentioned case-control study were selected for analysis of circulating MBL levels by double sandwich ELISA method. Mean MBL levels were compared between genotypic groups and multivariate regression was used to determine other independent factors influencing <it>MBL2 </it>expression.</p> <p>Results</p> <p>Our results confirm the effects of variant structural (B, C, and D) and promoter (H and Y) alleles that have been seen in other populations. In addition, MBL levels were found to be positively associated with male gender and hemoglobin A1c levels, but inversely related to triglyceride levels. Correlation was not found between MBL and other markers of inflammation.</p> <p>Conclusion</p> <p>New data is presented concerning the effects of known genetic variants on MBL levels in an American Indian population, as well as the relationship of <it>MBL2 </it>expression to clinical and environmental factors, including inflammatory markers.</p