Hydrogen-Related Conversion Processes of Ge-Related Point Defects in Silica Triggered by UV Laser Irradiation

The conversion processes of Ge-related point defects triggered in amorphous SiO2 by 4.7eV laser exposure were investigated. Our study has focused on the interplay between the (=Ge•-H) H(II) center and the twofold coordinated Ge defect (=Ge••). The former is generated in the post-irradiation stage, while the latter decays both during and after exposure. The post-irradiation decay kinetics of =Ge•• is isolated and found to be anti-correlated to the growth of H(II), at least at short times. From this finding it is suggested that both processes are due to trapping of radiolytic H0 at the diamagnetic defect site. Furthermore, the anti-correlated behavior is preserved also under repeated irradiation: light at 4.7eV destroys the already formed H(II) centers and restore their precursors =Ge••. This process leads to repeatability of the post-irradiation kinetics of the two species after multiple laser exposures. A comprehensive scheme of chemical reactions explaining the observed post-irradiation processes is proposed and tested against experimental data.Comment: 25 pages, 7 figures, submitted to Phys. Rev.

Health education in the public schools of Hawaii

This thesis will trace the major developments in the field of health education in the public schools or the Territory of Hawaii from the beginnings made in 1009 to the present time. Some attention will be paid to developments on the Islands or Hawaii, Maui, and Kauai; but the greater emphasis will be placed on the work done on the Island of Oahu. The public schools of the Territory of Hawaii are at present carrying on an extensive health program. The special health class work seems to be receiving more attention in the non-English standard schools. The need is more pronounced in these schools than in the English standard schools, and this, no doubt, accounts for the greater degree of interest shown. Perhaps the greatest progress has been made in some of the plantation schools. While these schools are a part of the public school system, they are also an integral part of the plantation community. In many instances, the entire school population of a plantation school is made up entirely of children whose parents work on the plantation. The officials on the plantation are vitally interested in the welfare of their workers and their families, and they are eager to do all that is possible to improve health conditions. This study is based on information obtained on several trips to Hawaii. It includes observations, made over a period of more than three years and experiences as an exchange teacher in a health class at Ewa, Oahu

PD-1 as a potential target in cancer therapy

Recently, an improved understanding of the molecular mechanisms governing the host response to tumors has led to the identification of checkpoint signaling pathways involved in limiting the anticancer immune response. One of the most critical checkpoint pathways responsible for mediating tumor-induced immune suppression is the programmed death-1 (PD-1) pathway, normally involved in promoting tolerance and preventing tissue damage in settings of chronic inflammation. Many human solid tumors express PD ligand 1 (PD-L1), and this is often associated with a worse prognosis. Tumor-infiltrating lymphocytes from patients with cancer typically express PD-1 and have impaired antitumor functionality. Proof-of-concept has come from several preclinical studies in which blockade of PD-1 or PD-L1 enhanced T-cell function and tumor cell lysis. Three monoclonal antibodies against PD-1, and one against PD-L1, have reported phase 1 data. All four agents have shown encouraging preliminary activity, and those that have been evaluated in larger patient populations appear to have encouraging safety profiles. Additional data are eagerly awaited. This review summarizes emerging clinical data and potential of PD-1 pathway–targeted antibodies in development. If subsequent investigations confirm the initial results, it is conceivable that agents blocking the PD-1/PD-L1 pathway will prove valuable additions to the growing armamentarium of targeted immunotherapeutic agents. Next-generation immunotherapy agents that target the PD-1 checkpoint pathway are demonstrating antitumor activity and encouraging safety profiles in early clinical trials. Current and future clinical trials will provide new insights, and the evaluation of biomarkers and rational combination therapies is ongoing

Ribosomal frameshifting in decoding antizyme mRNAs from yeast and protists to humans: close to 300 cases reveal remarkable diversity despite underlying conservation

The protein antizyme is a negative regulator of intracellular polyamine levels. Ribosomes synthesizing antizyme start in one ORF and at the codon 5′ adjacent to its stop codon, shift +1 to a second and partially overlapping ORF which encodes most of the protein. The ribosomal frameshifting is a sensor and effector of an autoregulatory circuit which is conserved in animals, fungi and protists. Stimulatory signals encoded 5′ and 3′ of the shift site act to program the frameshifting. Despite overall conservation, many individual branches have evolved specific features surrounding the frameshift site. Among these are RNA pseudoknots, RNA stem-loops, conserved primary RNA sequences, nascent peptide sequences and branch-specific ‘shifty’ codons

A case for a CUG-initiated coding sequence overlapping torovirus ORF1a and encoding a novel 30 kDa product

The genus Torovirus (order Nidovirales) includes a number of species that infect livestock. These viruses have a linear positive-sense ssRNA genome of ~25-30 kb, encoding a large polyprotein that is expressed from the genomic RNA, and several additional proteins expressed from a nested set of 3'-coterminal subgenomic RNAs. In this brief report, we describe the bioinformatic discovery of a new, apparently coding, ORF that overlaps the 5' end of the polyprotein coding sequence, ORF1a, in the +2 reading frame. The new ORF has a strong coding signature and, in fact, is more conserved at the amino acid level than the overlapping region of ORF1a. We propose that the new ORF utilizes a non-AUG initiation codon - namely a conserved CUG codon in a strong Kozak context - upstream of the ORF1a AUG initiation codon, resulting in a novel 258 amino acid protein, dubbed '30K'

A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1' may derive from ribosomal frameshifting

Japanese encephalitis, West Nile, Usutu and Murray Valley encephalitis viruses form a tight subgroup within the larger Flavivirus genus. These viruses utilize a single-polyprotein expression strategy, resulting in ~10 mature proteins. Plotting the conservation at synonymous sites along the polyprotein coding sequence reveals strong conservation peaks at the very 5' end of the coding sequence, and also at the 5' end of the sequence encoding the NS2A protein. Such peaks are generally indicative of functionally important non-coding sequence elements. The second peak corresponds to a predicted stable pseudoknot structure whose biological importance is supported by compensatory mutations that preserve the structure. The pseudoknot is preceded by a conserved slippery heptanucleotide (Y CCU UUU), thus forming a classical stimulatory motif for -1 ribosomal frameshifting. We hypothesize, therefore, that the functional importance of the pseudoknot is to stimulate a portion of ribosomes to shift -1 nt into a short (45 codon), conserved, overlapping open reading frame, termed foo. Since cleavage at the NS1-NS2A boundary is known to require synthesis of NS2A in cis, the resulting transframe fusion protein is predicted to be NS1-NS2AN-term-FOO. We hypothesize that this may explain the origin of the previously identified NS1 'extension' protein in JEV-group flaviviruses, known as NS1'

Interview with Barbara Atkins and Janet Mitchell by Andrea L’Hommedieu

Biographical NoteBarbara (Mitchell) Atkins was born in July, 1935, in Waterville, Maine. She grew up with four older brothers: John, Paul, Robert, and George Mitchell (Sr.). Her mother, Mintaha, was a weaver in the woolen mills in Waterville, and her father, George, Sr., was with the Central Maine Power Company and with the Colby College maintenance department. The family practiced the Maronite Roman Catholic rite of Lebanese descent. Her mother was born in Lebanon and immigrated in 1920. Barbara attended St. Joseph’s elementary school, Waterville Junior High School, and Waterville High School, where she played volleyball, basketball, was a cheerleader, a member of the French Club, and edited the yearbook. She earned her degree at the University of Maine, Orono, majoring in sociology. She married Edward L. Atkins, who had a printing and photography business; Barbara managed the office staff for her husband’s business when she wasn’t teaching. Edward Atkins was a devout Democrat, although he came from a Republican family. Janet (Fraser) Mitchell was born December 5, 1931, near Westbrook, Maine. When she was fifteen she and her family moved to Waterville, Maine, where she attended Waterville High School in the same class as George Mitchell. She married Robbie Mitchell, George Mitchell’s older brother. She lives in Waterville. SummaryInterview includes discussion of: growing up in Waterville; the Lebanese community in Waterville; Barbara attending class with her brother George when they were young; their parents’ interest in the children’s education; Janet Mitchell’s welcome to the Mitchell family; an anecdote about George Mitchell bringing Janet’s mother a Christmas tree; an anecdote about George and Robert Mitchell working together at the Boys Club; Eddie Atkins; an anecdote about George Mitchell practicing at home to read the Epistle as an altar boy; Mitchell family gatherings; Robbie Mitchell; the Mitchell brothers playing cribbage; Mr. and Mrs. Mitchell; Mrs. Mitchell’s baking; the goat milk story; story of George Mitchell giving his brother Robbie a car; George Mitchell’s time doing counter-intelligence work; turning down the Supreme Court judgeship; their aspirations that he would be president; and the good qualities of the people of Maine

Bioinformatic analysis suggests that the Cypovirus 1 major core protein cistron harbours an overlapping gene

Members of the genus Cypovirus (family Reoviridae) are common pathogens of insects. These viruses have linear dsRNA genomes divided into 10–11 segments, which have generally been assumed to be monocistronic. Here, bioinformatic evidence is presented for a short overlapping coding sequence (CDS) in the cypovirus genome segment encoding the major core capsid protein VP1, overlapping the 5'-terminal region of the VP1 ORF in the +1 reading frame. In Cypovirus type 1 (CPV-1), a 62-codon AUG-initiated open reading frame (hereafter ORFX) is present in all four available segment 1 sequences. The pattern of base variations across the sequence alignment indicates that ORFX is subject to functional constraints at the amino acid level (even when the constraints due to coding in the overlapping VP1 reading frame are taken into account; MLOGD software). In fact the translated ORFX shows greater amino acid conservation than the overlapping region of VP1. The genomic location of ORFX is consistent with translation via leaky scanning. A 62–64 codon AUG-initiated ORF is present in a corresponding location and reading frame in other available cypovirus sequences (2 CPV-14, 1 CPV-15) and an 87-codon ORFX homologue may also be present in Aedes pseudoscutellaris reovirus. The ORFX amino acid sequences are hydrophilic and basic, with between 12 and 16 Arg/Lys residues in each though, at 7.5–10.2 kDa, the putative ORFX product is too small to appear on typical published protein gels

High-order harmonic generation from polyatomic molecules including nuclear motion and a nuclear modes analysis

We present a generic approach for treating the effect of nuclear motion in the high-order harmonic generation from polyatomic molecules. Our procedure relies on a separation of nuclear and electron dynamics where we account for the electronic part using the Lewenstein model and nuclear motion enters as a nuclear correlation function. We express the nuclear correlation function in terms of Franck-Condon factors which allows us to decompose nuclear motion into modes and identify the modes that are dominant in the high-order harmonic generation process. We show results for the isotopes CH$_4$ and CD$_4$ and thereby provide direct theoretical support for a recent experiment [Baker {\it et al.}, Science {\bf 312}, 424 (2006)] that uses high-order harmonic generation to probe the ultra-fast structural nuclear rearrangement of ionized methane.Comment: 6 pages, 6 figure