Report to the personnel board of the city of Melrose.

Thesis (M.B.A.)--Boston Universit

Search for correlation effects in linear chains of trapped ions

We report a precise search for correlation effects in linear chains of 2 and 3 trapped Ca+ ions. Unexplained correlations in photon emission times within a linear chain of trapped ions have been reported, which, if genuine, cast doubt on the potential of an ion trap to realize quantum information processing. We observe quantum jumps from the metastable 3d 2D_{5/2} level for several hours, searching for correlations between the decay times of the different ions. We find no evidence for correlations: the number of quantum jumps with separations of less than 10 ms is consistent with statistics to within errors of 0.05%; the lifetime of the metastable level derived from the data is consistent with that derived from independent single-ion data at the level of the experimental errors 1%; and no rank correlations between the decay times were found with sensitivity to rank correlation coefficients at the level of |R| = 0.024.Comment: With changes to introduction. 5 pages, including 4 figures. Submitted to Europhys. Let

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Prophylactic acyclovir effectively reduces herpes simplex virus type 1 reactivation after exposure of latently infected mice to ultraviolet

\ Purpose. To determine the potential efficacy and anatomic sites of action of prophylactic oral acyclovir using a murine model of ultraviolet-B-induced reactivation of herpes simplex 1 keratitis. Methods. Latent infection with herpes simplex 1 (McKrae) was established in 80 National Institutes of Health inbred strain of mice. Forty of the mice were given acyclovir orally and the other 40 latently infected mice served as controls. Mice were exposed to 250 mj/cm 2 of ultraviolet-B radiation and killed on days 1,2,3, and 4 after ultraviolet-B radiation. Trigeminal ganglia and eyes from these mice were homogenized and incubated on Vero cell monolayers for recovery of reactivated virus. Results. Based on the recovery of infectious virus after ultraviolet-B in treated versus control groups, acyclovir effectively reduced detectable viral reactivation at both the ocular level (P = 0.003) and the ganglionic level (P = 0.025). The numbers of viral culture-positive eye and trigeminal ganglia homogenates in the control group were 11 and 6 out of 40, respectively, compared to 1 and 0 out of 40 culture-positive eye and trigeminal ganglia homogenates in the acyclovir treated mice. Therapeutic serum levels of acyclovir were confirmed by high performance liquid chromatography. In the acyclovir-tested group, the single case of viral breakthrough at the ocular surface was not an acyclovir-resistant mutant. Conclusion. Prophylactic acyclovir effectively reduces the incidence of herpes simplex virus-1 reactivation after ultraviolet-B-induced reactivation in National Institutes of Health inbred strain of mice. Invest Ophthalmol Vis Sci. 1993; 34:3459-3465. .Despite the development and widespread use of antiviral drugs, herpes simplex eye disease remains the most common cause of infectious blindness in the United States. 1 Acyclovir (ACV) is a potent, relatively nontoxic compound with specific antiviral activity against a number of herpes group viruses, including herpes simplex virus-1 (HSV-1 ). 2>3 The selectivity of ACV as an antiviral agent is based on its preferential activation by an HSV-encoded thymidine kinase, resulting in potent inhibition of the viral DNA polymerase. Three investigations assessing the effect of systemic ACV in HSV-1 keratitis using animal reactivation models have yielded conflicting results. " 7 Each study used New Zealand white rabbits and the McKrae strain of virus. The studies differed, however, in the route and duration of ACV delivery and reactivation stimulus, as well as the method of detection of viral reactivation. In one study, 5 oral ACV at a concentration of 1 mg/ml in drinking water was not effective in reducing the "spontaneous" recurrence of viral shedding or clinical corneal disease in rabbits latently infected with HSV-1. A second study focused on latentl