Stringent Nucleotide Recognition by the Ribosome at the Middle Codon Position.

Accurate translation of the genetic code depends on mRNA:tRNA codon:anticodon base pairing. Here we exploit an emissive, isosteric adenosine surrogate that allows direct measurement of the kinetics of codon:anticodon University of California base formation during protein synthesis. Our results suggest that codon:anticodon base pairing is subject to tighter constraints at the middle position than at the 5'- and 3'-positions, and further suggest a sequential mechanism of formation of the three base pairs in the codon:anticodon helix

Building a Document Corpus for Manufacturing Knowledge Retrieval

When faced with challenging technical problems, R&D personnel would often turn to technical papers to seek inspiration for a solution. The building of a corpus of such papers and the easy retrieval of relevant papers by the user in his query is an area that has not been systematically dealt with. This is an attempt to build such a corpus for manufacturing R&D personnel. Manufacturing Corpus Version 1 (MCV1) is an archive of more than 1400 relevant manufacturing engineering papers between 1998 and 2000. In this paper, the origins and motivation of building MCV1 is discussed. The innovative coding process which is specially designed for manufacturing companies will be presented. All other relevant issues, like coding policy, category codes and input documents, will be explained. Finally, two quality indicators which integrate all concerns about coding quality will be examined.Singapore-MIT Alliance (SMA

Calixarene-decorated liposomes for intracellular cargo delivery

Amphiphilic calix[4]arenes, functionalized with guanidinium groups, are used to decorate the outer surface of liposomes and significantly improve the cellular uptake of a cargo compared to plain liposomes. The improved uptake is elicited and mediated by the interaction between the cationic polar heads of the macrocycle units embedded in the liposome bilayer and anionic heparan-sulfate proteoglycans surrounding the exterior of cells

An Innovative Model of Culturally Tailored Health Promotion Groups for Cambodian Survivors of Torture

Cambodians living in the U.S.A. suffer from depression, posttraumatic stress disorder (PTSD), and chronic medical disease at rates far in excess of national averages. The Harvard Program in Refugee Trauma’s Cambodian Health Promotion Program seeks to address this burden of disease by offering them culturally tailored health education in a group setting. A health professional and a bicultural health educator co-facilitated a five-session health promotion group for Cambodian survivors of torture from 2007 to 2011. The program covered five major topics from Western and Cambodian worldviews. They included the meaning of health promotion, nutrition, exercise, stress management and sleep hygiene, and health practitioner-patient communication. The bicultural worker administered Pre and Post semi-structured Health Promotion Questionnaires. The data presented here are the results from 126 participants. Changes between the Pre and Post health promotion groups demonstrated significant improvements in health status, lifestyle activities, sleep, and depression. Participants revealed greater confidence in communicating with their primary health care practitioner. Culturally tailored Cambodian health promotion education administered in a small group setting may improve health and mental health behaviors. Culturally tailored health promotion education in a small group setting may promote healing in survivors of torture. It is an intervention worthy of further research and development

A triple helix stabilizes the 3' ends of long noncoding RNAs that lack poly(A) tails

The MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) locus is misregulated in many human cancers and produces an abundant long nuclear-retained noncoding RNA. Despite being transcribed by RNA polymerase II, the 3' end of MALAT1 is produced not by canonical cleavage/polyadenylation but instead by recognition and cleavage of a tRNA-like structure by RNase P. Mature MALAT1 thus lacks a poly(A) tail yet is expressed at a level higher than many protein-coding genes in vivo. Here we show that the 3' ends of MALAT1 and the MEN beta long noncoding RNAs are protected from 3'-5' exonucleases by highly conserved triple helical structures. Surprisingly, when these structures are placed downstream from an ORF, the transcript is efficiently translated in vivo despite the lack of a poly(A) tail. The triple helix therefore also functions as a translational enhancer, and mutations in this region separate this translation activity from simple effects on RNA stability or transport. We further found that a transcript ending in a triple helix is efficiently repressed by microRNAs in vivo, arguing against a major role for the poly(A) tail in microRNA-mediated silencing. These results provide new insights into how transcripts that lack poly(A) tails are stabilized and regulated and suggest that RNA triple-helical structures likely have key regulatory functions in vivo

Calculation of the Coherent Synchrotron Radiation Impedance from a Wiggler

Most studies of Coherent Synchrotron Radiation (CSR) have only considered the radiation from independent dipole magnets. However, in the damping rings of future linear colliders, a large fraction of the radiation power will be emitted in damping wigglers. In this paper, the longitudinal wakefield and impedance due to CSR in a wiggler are derived in the limit of a large wiggler parameter $K$. After an appropriate scaling, the results can be expressed in terms of universal functions, which are independent of $K$. Analytical asymptotic results are obtained for the wakefield in the limit of large and small distances, and for the impedance in the limit of small and high frequencies.Comment: 10 pages, 8 figure

Cytotoxic T lymphocyte responses against melanocytes and melanoma

<p>Abstract</p> <p>Background</p> <p>Vitiligo is a common toxicity associated with immunotherapy for melanoma. Cytotoxic T lymphocytes (CTLs) against melanoma commonly target melanoma-associated antigens (MAAs) which are also expressed by melanocytes. To uncouple vitiligo from melanoma destruction, it is important to understand if CTLs can respond against melanoma and melanocytes at different levels.</p> <p>Methods</p> <p>To understand the dichotomous role of MAA-specific CTL, we characterized the functional reactivities of established CTL clones directed to MAAs against melanoma and melanocyte cell lines.</p> <p>Results</p> <p>CTL clones generated from melanoma patients were capable of eliciting MHC-restricted, MAA-specific lysis against melanocyte cell lines as well as melanoma cells. Among the tested HLA-A*0201-restricted CTL clones, melanocytes evoked equal to slightly higher degranulation and cytolytic responses as compared to melanoma cells. Moreover, MAA-specific T cells from vaccinated patients responded directly ex vivo to melanoma and melanocytes. Melanoma cells express slightly higher levels of MART-1 and gp100 than melanocytes as measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry.</p> <p>Conclusions</p> <p>Our data suggest that CTLs respond to melanoma and melanocytes equally in vitro and directly ex vivo.</p