A monocysteine approach for analyzing the structure and interactions of the UmuD protein involved in SOS mutagenesis

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 1996.Includes bibliographical references.by Melissa Huei-I Lee.Ph.D

Saturn's Seasonal Atmosphere at Northern Summer Solstice

The incredible longevity of Cassini's orbital mission at Saturn has provided the most comprehensive exploration of a seasonal giant planet to date. This review explores Saturn's changing global temperatures, composition, and aerosol properties between northern spring and summer solstice (2015-2017), extending our previous review of Cassini's remote sensing investigations (2004-14, Fletcher et al., 2018) to the grand finale. The result is an unprecedented record of Saturn's climate that spans almost half a Saturnian year, which can be used to test the seasonal predictions of radiative climate models, neutral and ion photochemistry models, and atmospheric circulation models. Hemispheric asymmetries in tropospheric and stratospheric temperatures were observed to reverse from northern winter to northern summer; spatial distributions of hydrocarbons and para-hydrogen shifted in response to atmospheric dynamics (e.g., seasonally-reversing Hadley cells, polar stratospheric vortex formation, equatorial stratospheric oscillations, and inter-hemispheric transport); and upper tropospheric and stratospheric aerosols exhibited changes in optical thickness that modulated Saturn's visible colours (from blue hues to a golden appearance in the north near solstice), reflectivity, and near-infrared emission. Numerical simulations of radiative balance and photochemistry do a good job in reproducing the observed seasonal change and phase lags, but discrepancies between models and observations still persist, indicating a crucial role for atmospheric dynamics and the need to couple chemical and radiative schemes to the next generation of circulation models. With Cassini's demise, an extended study of Saturn's seasons, from northern summer to autumn, will require the capabilities of ground- and space-based observatories, as we eagerly await the next orbital explorer at Saturn.Comment: 24 pages, 18 figures, submitted for publication by Cambridge University Press as part of a multi-volume work edited by Kevin Baines, Michael Flasar, Norbert Krupp, and Thomas Stallard, entitled "Cassini at Saturn: The Grand Finale." The copy of the Chapter, as displayed on this website, is a draft, pre-publication copy onl

A method for encoding clinical datasets with SNOMED CT

<p>Abstract</p> <p>Background</p> <p>Over the past decade there has been a growing body of literature on how the Systematised Nomenclature of Medicine Clinical Terms (SNOMED CT) can be implemented and used in different clinical settings. Yet, for those charged with incorporating SNOMED CT into their organisation's clinical applications and vocabulary systems, there are few detailed encoding instructions and examples available to show how this can be done and the issues involved. This paper describes a heuristic method that can be used to encode clinical terms in SNOMED CT and an illustration of how it was applied to encode an existing palliative care dataset.</p> <p>Methods</p> <p>The encoding process involves: identifying input data items; cleaning the data items; encoding the cleaned data items; and exporting the encoded terms as output term sets. Four outputs are produced: the SNOMED CT reference set; interface terminology set; SNOMED CT extension set and unencodeable term set.</p> <p>Results</p> <p>The original palliative care database contained 211 data elements, 145 coded values and 37,248 free text values. We were able to encode ~84% of the terms, another ~8% require further encoding and verification while terms that had a frequency of fewer than five were not encoded (~7%).</p> <p>Conclusions</p> <p>From the pilot, it would seem our SNOMED CT encoding method has the potential to become a general purpose terminology encoding approach that can be used in different clinical systems.</p

Energetic Components of Cooperative Protein Folding

A new lattice protein model with a four-helix bundle ground state is analyzed by a parameter-space Monte Carlo histogram technique to evaluate the effects of an extensive variety of model potentials on folding thermodynamics. Cooperative helical formation and contact energies based on a 5-letter alphabet are found to be insufficient to satisfy calorimetric and other experimental criteria for two-state folding. Such proteinlike behaviors are predicted, however, by models with polypeptide-like local conformational restrictions and environment-dependent hydrogen bonding-like interactions.Comment: 11 pages, 4 postscripts figures, Phys. Rev. Lett. (in press

Enhancement of radiosensitivity in human glioblastoma cells by the DNA N-mustard alkylating agent BO-1051 through augmented and sustained DNA damage response

<p>Abstract</p> <p>Background</p> <p>1-{4-[Bis(2-chloroethyl)amino]phenyl}-3-[2-methyl-5-(4-methylacridin-9-ylamino)phenyl]urea (BO-1051) is an N-mustard DNA alkylating agent reported to exhibit antitumor activity. Here we further investigate the effects of this compound on radiation responses of human gliomas, which are notorious for the high resistance to radiotherapy.</p> <p>Methods</p> <p>The clonogenic assay was used to determine the IC₅₀and radiosensitivity of human glioma cell lines (U87MG, U251MG and GBM-3) following BO-1051. DNA histogram and propidium iodide-Annexin V staining were used to determine the cell cycle distribution and the apoptosis, respectively. DNA damage and repair state were determined by γ-H2AX foci, and mitotic catastrophe was measure using nuclear fragmentation. Xenograft tumors were measured with a caliper, and the survival rate was determined using Kaplan-Meier method.</p> <p>Results</p> <p>BO-1051 inhibited growth of human gliomas in a dose- and time-dependent manner. Using the dosage at IC₅₀, BO-1051 significantly enhanced radiosensitivity to different extents [The sensitizer enhancement ratio was between 1.24 and 1.50 at 10% of survival fraction]. The radiosensitive G₂/M population was raised by BO-1051, whereas apoptosis and mitotic catastrophe were not affected. γ-H2AX foci was greatly increased and sustained by combined BO-1051 and γ-rays, suggested that DNA damage or repair capacity was impaired during treatment. <it>In vivo </it>studies further demonstrated that BO-1051 enhanced the radiotherapeutic effects on GBM-3-beared xenograft tumors, by which the sensitizer enhancement ratio was 1.97. The survival rate of treated mice was also increased accordingly.</p> <p>Conclusions</p> <p>These results indicate that BO-1051 can effectively enhance glioma cell radiosensitivity <it>in vitro </it>and <it>in vivo</it>. It suggests that BO-1051 is a potent radiosensitizer for treating human glioma cells.</p

Analyzing 13 Years of Cetacean Strandings: Multiple Stressors to Cetaceans in Taiwanese Waters and Their Implications for Conservation and Future Research

This study summarizes the postmortem investigations of 73 cetaceans stranded on the coast of Taiwan between 2001 and 2013, including 51 Delphinidae, 17 Kogiidae, 3 Ziphiidae, 1 Physeteridae, and 1 Balaenopteridae. Of these, eight (11%) were categorized into direct human-related strandings, including fisheries interaction (bycatch), vessel collision and other anthropogenic-related pathology. Gastrointestinal foreign bodies were found in eight individuals (11%). Most of the bacteria isolated from stranded dolphins were zoonotic pathogens including extended-spectrum β-lactamases Escherichia coli, which indicates waste pollution from land. Severe parasite infestation was found in 36 of the cases (49%), which suggests that the immune function could be compromised. Thirty-eight cases (52%) were diagnosed with myocardial patchy fibrosis or dilated cardiomyopathy. The evidence shown here indicates that cetaceans around Taiwanese waters may suffer from multiple stressors. This study provides baseline data for the health assessment of cetacean populations in Taiwan, which may ultimately provide recommendations for future cetacean conservation and research throughout the western Pacific

A Direct Comparison of Two Densely Sampled HIV Epidemics: The UK and Switzerland

Phylogenetic clustering approaches can elucidate HIV transmission dynamics. Comparisons across countries are essential for evaluating public health policies. Here, we used a standardised approach to compare the UK HIV Drug Resistance Database and the Swiss HIV Cohort Study while maintaining data-protection requirements. Clusters were identified in subtype A1, B and C pol phylogenies. We generated degree distributions for each risk group and compared distributions between countries using Kolmogorov-Smirnov (KS) tests, Degree Distribution Quantification and Comparison (DDQC) and bootstrapping. We used logistic regression to predict cluster membership based on country, sampling date, risk group, ethnicity and sex. We analysed >8,000 Swiss and >30,000 UK subtype B sequences. At 4.5% genetic distance, the UK was more clustered and MSM and heterosexual degree distributions differed significantly by the KS test. The KS test is sensitive to variation in network scale, and jackknifing the UK MSM dataset to the size of the Swiss dataset removed the difference. Only heterosexuals varied based on the DDQC, due to UK male heterosexuals who clustered exclusively with MSM. Their removal eliminated this difference. In conclusion, the UK and Swiss HIV epidemics have similar underlying dynamics and observed differences in clustering are mainly due to different population sizes

The ARGO-YBJ Experiment Progresses and Future Extension

Gamma ray source detection above 30TeV is an encouraging approach for finding galactic cosmic ray origins. All sky survey for gamma ray sources using wide field of view detector is essential for population accumulation for various types of sources above 100GeV. To target the goals, the ARGO-YBJ experiment has been established. Significant progresses have been made in the experiment. A large air shower detector array in an area of 1km2 is proposed to boost the sensitivity. Hybrid detection with multi-techniques will allow a good discrimination between different types of primary particles, including photons and protons, thus enable an energy spectrum measurement for individual specie. Fluorescence light detector array will extend the spectrum measurement above 100PeV where the second knee is located. An energy scale determined by balloon experiments at 10TeV will be propagated to ultra high energy cosmic ray experiments