The Strength of B Cell Interaction with Antigen Determines the Degree of IgM Polymerization

The induction of variable disulfide polymerization of IgM in the trout (Oncorhynchus mykiss) and its effect on its half-life were examined. An association between greater Ab affinity and increased disulfide polymerization was first indicated by the observation of this increased IgM disulfide polymerization during the process of affinity maturation. A direct association between Ab affinity and disulfide polymerization was then established by the fractionation of individual sera into high- and low-affinity subpopulations, which also resulted in the partitioning of high and low degrees of disulfide polymerization. The ability of high-affinity B cells to produce more highly polymerized Abs upon Ag induction was demonstrated by in vitro Ag-driven selection. Low Ag concentrations, which elicited only high-affinity Abs, also possessed the highest degree of polymerization, whereas higher concentrations of Ag elicited a broader array of Ab affinities, yielding a lower average affinity and degree of polymerization. Half-life studies revealed that the high-affinity, highly polymerized Abs possessed longer half-lives than the lower-affinity, lightly polymerized Abs. Finally, although the affinity for Ag is associated with elevated levels of polymerization, analysis of naive Ig revealed that the degree of polymerization alone, not affinity, appears sufficient to prolong Ig half-life. The Journal of Immunology, 2010,184: 844-850

Bioinformatics advances in saliva diagnostics

There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance basic, translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval, integration and analysis of data, we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in saliva diagnostics made possible by the Saliva Ontology and SDxMart

The association of chromosome 8p deletion and tumor metastasis in human hepatocellular carcinoma

Program no. 686postprin

The effect of cigarette price increase on the cigarette consumption in Taiwan: evidence from the National Health Interview Surveys on cigarette consumption

BACKGROUND: This study uses cigarette price elasticity to evaluate the effect of a new excise tax increase on cigarette consumption and to investigate responses from various types of smokers. METHODS: Our sample consisted of current smokers between 17 and 69 years old interviewed during an annual face-to-face survey conducted by Taiwan National Health Research Institutes between 2000 to 2003. We used Ordinary Least Squares (OLS) procedure to estimate double logarithmic function of cigarette demand and cigarette price elasticity. RESULTS: In 2002, after Taiwan had enacted the new tax scheme, cigarette price elasticity in Taiwan was found to be -0.5274. The new tax scheme brought about an average annual 13.27 packs/person (10.5%) reduction in cigarette consumption. Using the cigarette price elasticity estimate from -0.309 in 2003, we calculated that if the Health and Welfare Tax were increased by another NT$ 3 per pack and cigarette producers shifted this increase to the consumers, cigarette consumption would be reduced by 2.47 packs/person (2.2%). The value of the estimated cigarette price elasticity is smaller than one, meaning that the tax will not only reduce cigarette consumption but it will also generate additional tax revenues. Male smokers who had no income or who smoked light cigarettes were found to be more responsive to changes in cigarette price. CONCLUSIONS: An additional tax added to the cost of cigarettes would bring about a reduction in cigarette consumption and increased tax revenues. It would also help reduce incidents smoking-related illnesses. The additional tax revenues generated by the tax increase could be used to offset the current financial deficiency of Taiwan's National Health Insurance program and provide better public services

Practical implementation, characterization and applications of a multi-colour time-gated luminescence microscope

Time-gated luminescence microscopy using long-lifetime molecular probes can effectively eliminate autofluorescence to enable high contrast imaging. Here we investigate a new strategy of time-gated imaging for simultaneous visualisation of multiple species of microorganisms stained with long-lived complexes under low-background conditions. This is realized by imaging two pathogenic organisms (Giardia lamblia stained with a red europium probe and Cryptosporidium parvum with a green terbium probe) at UV wavelengths (320-400 nm) through synchronization of a flash lamp with high repetition rate (1 kHz) to a robust time-gating detection unit. This approach provides four times enhancement in signal-to-background ratio over non-time-gated imaging, while the average signal intensity also increases six-fold compared with that under UV LED excitation. The high sensitivity is further confirmed by imaging the single europium-doped Y2O2S nanocrystals (150 nm). We report technical details regarding the time-gating detection unit and demonstrate its compatibility with commercial epi-fluorescence microscopes, providing a valuable and convenient addition to standard laboratory equipment

Tuneable Singlet Exciton Fission and Triplet-Triplet Annihilation in an Orthogonal Pentacene Dimer

We report fast and highly efficient intramolecular singlet exciton fission in a pentacene dimer, consisting of two covalently attached, nearly orthogonal pentacene units. Fission to triplet excitons from this ground state geometry occurs within 1 ps in isolated molecules in solution and dispersed solid matrices. The process exhibits a sensitivity to environmental polarity and competes with geometric relaxation in the singlet state, while subsequent triplet decay is strongly dependent on conformational freedom. The near orthogonal arrangement of the pentacene units is unlike any structure currently proposed for efficient singlet exciton fission and may lead to new molecular design rules.JW acknowledges financial support from Singapore MOE Tier 3 grant (MOE2014-T3-1-004). SL thanks AGS Scholarship support from the A*STAR Singapore. The work was supported by the EPSRC (grant number EP/G060738/1). We acknowledge the use of the Darwin Supercomputer of the University of Cambridge High 18 Performance Computing Service (http://www.hpc.cam.ac.uk/) and the EPSRC UK National Service for Computational Chemistry Software (NSCCS) at Imperial College London in carrying out this work.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/adfm.20150153

Bi-local Construction of Sp(2N)/dS Higher Spin Correspondence

We derive a collective field theory of the singlet sector of the Sp(2N) sigma model. Interestingly the hamiltonian for the bilocal collective field is the same as that of the O(N) model. However, the large-N saddle points of the two models differ by a sign. This leads to a fluctuation hamiltonian with a negative quadratic term and alternating signs in the nonlinear terms which correctly reproduces the correlation functions of the singlet sector. Assuming the validity of the connection between O(N) collective fields and higher spin fields in AdS, we argue that a natural interpretation of this theory is by a double analytic continuation, leading to the dS/CFT correspondence proposed by Anninos, Hartman and Strominger. The bi-local construction gives a map into the bulk of de Sitter space-time. Its geometric pseudospin-representation provides a framework for quantization and definition of the Hilbert space. We argue that this is consistent with finite N grassmanian constraints, establishing the bi-local representation as a nonperturbative framework for quantization of Higher Spin Gravity in de Sitter space.Comment: 1 figur

DNA topoisomerases participate in fragility of the oncogene RET

Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication

Bisphenol A exposure in Mexico City and risk of prematurity: a pilot nested case control study

Abstract Background Presence of Bisphenol A (BPA) has been documented worldwide in a variety of human biological samples. There is growing evidence that low level BPA exposure may impact placental tissue development and thyroid function in humans. The aim of this present pilot study was to determine urinary concentrations of BPA during the last trimester of pregnancy among a small subset of women in Mexico City, Mexico and relate these concentrations to risk of delivering prematurely. Methods A nested case-control subset of 60 participants in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) study in Mexico City, Mexico were selected based on delivering less than or equal to 37 weeks of gestation and greater than 37 weeks of gestation. Third trimester archived spot urine samples were analyzed by online solid phase extraction coupled with high performance liquid chromatography isotope dilution tandem mass spectrometry. Results BPA was detected in 80.0% (N = 48) of the urine samples; total concentrations ranged from < 0.4 μg/L to 6.7 μg/L; uncorrected geometric mean was 1.52 μg/L. The adjusted odds ratio of delivering less than or equal to 37 weeks in relation to specific gravity adjusted third trimester BPA concentration was 1.91 (95%CI 0.93, 3.91, p-value = 0.08). When cases were further restricted to births occurring prior to the 37th week (n = 12), the odds ratio for specific-gravity adjusted BPA was larger and statistically significant (p < 0.05). Conclusions This is the first study to document measurable levels of BPA in the urine of a population of Mexican women. This study also provides preliminary evidence, based on a single spot urine sample collected during the third trimester, that pregnant women who delivered less than or equal to 37 weeks of gestation and prematurely (< 37 weeks) had higher urinary concentrations of BPA compared to women delivering after 37 weeks.http://deepblue.lib.umich.edu/bitstream/2027.42/78251/1/1476-069X-9-62.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78251/2/1476-069X-9-62.pdfPeer Reviewe