Fast and efficient optical phase conjunction using a degenerate Raman System in rubidium

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1997.Includes bibliographical references (p. 69).by Darren S. Hsiung.M.Eng

Thermodynamic curvature measures interactions

Thermodynamic fluctuation theory originated with Einstein who inverted the relation $S=k_B\ln\Omega$ to express the number of states in terms of entropy: $\Omega= \exp(S/k_B)$. The theory's Gaussian approximation is discussed in most statistical mechanics texts. I review work showing how to go beyond the Gaussian approximation by adding covariance, conservation, and consistency. This generalization leads to a fundamentally new object: the thermodynamic Riemannian curvature scalar $R$, a thermodynamic invariant. I argue that $|R|$ is related to the correlation length and suggest that the sign of $R$ corresponds to whether the interparticle interactions are effectively attractive or repulsive.Comment: 29 pages, 7 figures (added reference 27

Synergistic effect of phosphodiesterase 4 inhibitor and serum on migration of endotoxin-stimulated macrophages.

Macrophage migration is an essential step in host defense against infection and wound healing. Elevation of cAMP by inhibiting phosphodiesterase 4 (PDE4), enzymes that specifically degrade cAMP, is known to suppress various inflammatory responses in activated macrophages, but the role of PDE4 in macrophage migration is poorly understood. Here we show that the migration of Raw 264.7 macrophages stimulated with LPS was markedly and dose-dependently induced by the PDE4 inhibitor rolipram as assessed by scratch wound healing assay. Additionally, this response required the involvement of serum in the culture medium as serum starvation abrogated the effect. Further analysis revealed that rolipram and serum exhibited synergistic effect on the migration, and the influence of serum was independent of PDE4 mRNA expression in LPS-stimulated macrophages. Moreover, the enhanced migration by rolipram was mediated by activating cAMP/exchange proteins directly activated by cAMP (Epac) signaling, presumably via interaction with LPS/TLR4 signaling with the participation of unknown serum components. These results suggest that PDE4 inhibitors, together with serum components, may serve as positive regulators of macrophage recruitment for more efficient pathogen clearance and wound repair

In vivo tracking of phosphoinositides in Drosophila photoreceptors.

In order to monitor phosphoinositide turnover during phospholipase C (PLC)-mediated Drosophila phototransduction, fluorescently tagged lipid probes were expressed in photoreceptors and imaged both in dissociated cells, and in eyes of intact living flies. Of six probes tested, Tb(R332H) (a mutant of the Tubby protein pleckstrin homology domain) was judged the best reporter for phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2], and the P4M domain from Legionella SidM for phosphatidylinositol 4-phosphate (PtdIns4P). Using accurately calibrated illumination, we found that only ∼50% of PtdIns(4,5)P2 and very little PtdIns4P were depleted by full daylight intensities in wild-type flies, but both were severely depleted by ∼100-fold dimmer intensities in mutants lacking Ca(2+)-permeable transient receptor potential (TRP) channels or protein kinase C (PKC). Resynthesis of PtdIns4P (t½ ∼12 s) was faster than PtdIns(4,5)P2 (t½ ∼40 s), but both were greatly slowed in mutants of DAG kinase (rdgA) or PtdIns transfer protein (rdgB). The results indicate that Ca(2+)- and PKC-dependent inhibition of PLC is required for enabling photoreceptors to maintain phosphoinositide levels despite high rates of hydrolysis by PLC, and suggest that phosphorylation of PtdIns4P to PtdIns(4,5)P2 is the rate-limiting step of the cycle.This research was supported by grants from the BBSRC (BB/M00706/1 and BB/J009253/1; RCH, C-HL,ASR) and the Cambridge-Nehru Trust (SS).This is the final version of the article. It first appeared from The Company of Biologists via http://dx.doi.org/10.1242/jcs.18036

Contribution of Transcription Factor Binding Site Motif Variants to Condition-Specific Gene Expression Patterns in Budding Yeast

It is now experimentally well known that variant sequences of a cis transcription factor binding site motif can contribute to differential regulation of genes. We characterize the relationship between motif variants and gene expression by analyzing expression microarray data and binding site predictions. To accomplish this, we statistically detect motif variants with effects that differ among environments. Such environmental specificity may be due to either affinity differences between variants or, more likely, differential interactions of TFs bound to these variants with cofactors, and with differential presence of cofactors across environments. We examine conservation of functional variants across four Saccharomyces species, and find that about a third of transcription factors have target genes that are differentially expressed in a condition-specific manner that is correlated with the nucleotide at variant motif positions. We find good correspondence between our results and some cases in the experimental literature (Reb1, Sum1, Mcm1, and Rap1). These results and growing consensus in the literature indicates that motif variants may often be functionally distinct, that this may be observed in genomic data, and that variants play an important role in condition-specific gene regulation.</p

Single-nucleotide polymorphism-based genetic risk score and patient age at prostate cancer diagnosis

Importance: Few studies have evaluated the association between a single-nucleotide polymorphism-based genetic risk score (GRS) and patient age at prostate cancer (PCa) diagnosis. Objectives: To test the association between a GRS and patient age at PCa diagnosis and to compare the performance of a GRS with that of family history (FH) in PCa risk stratification. Design, Setting, and Participants: A cohort study of 3225 white men was conducted as a secondary analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) chemoprevention trial, a 4-year, randomized, double-blind, placebo-controlled multicenter study conducted from March 2003 to April 2009 to evaluate the safety and efficacy of dutasteride in reducing PCa events. Participants were confirmed to be cancer free by prostate biopsy (6-12 cores) within 6 months prior to the study and underwent 10 core biopsies every 2 years per protocol. The dates for performing data analysis were from July 2016 to October 2019. Interventions: A well-established, population-standardized GRS was calculated for each participant based on 110 known PCa risk-associated single-nucleotide polymorphisms, which is a relative risk compared with the general population. Men were classified into 3 GRS risk groups based on predetermined cutoff values: low (\u3c0.50), average (0.50-1.49), and high (≥1.50). Main Outcomes and Measures: Prostate cancer diagnosis-free survival among men of different risk groups. Results: Among 3225 men (median age, 63 years [interquartile range, 58-67 years]) in the study, 683 (21%) were classified as low risk, 1937 (60%) as average risk, and 605 (19%) as high risk based on GRS alone. In comparison, 2789 (86%) were classified as low or average risk and 436 (14%) as high risk based on FH alone. Men in higher GRS risk groups had a PCa diagnosis-free survival rate that was worse than that of those in the lower GRS risk group (χ2 = 53.3; P \u3c .001 for trend) and in participants with a negative FH of PCa (χ2 = 45.5; P \u3c .001 for trend). Combining GRS and FH further stratified overall genetic risk, indicating that 957 men (30%) were at high genetic risk (either high GRS or positive FH), 1667 men (52%) were at average genetic risk (average GRS and negative FH), and 601 men (19%) were at low genetic risk (low GRS and negative FH). The median PCa diagnosis-free survival was 74 years (95% CI, 73-75 years) for men at high genetic risk, 77 years (95% CI, 75 to \u3e80 years) for men at average genetic risk, and more than 80 years (95% CI, \u3e80 to \u3e80 years) for men at low genetic risk. In contrast, the median PCa diagnosis-free survival was 73 years (95% CI, 71-76 years) for men with a positive FH and 77 years (95% CI, 76-79 years) for men with a negative FH. Conclusions and Relevance: This study suggests that a GRS is significantly associated with patient age at PCa diagnosis. Combining FH and GRS may better stratify inherited risk than FH alone for developing personalized PCa screening strategies