Design and synthesis of conjugated macrocycles and polymers

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010.Vita. Page 208 blank. Cataloged from PDF version of thesis.Includes bibliographical references.The design, synthesis and characterization of conjugated macrocycles and polymers are presented in this dissertation. In particular, work involving the exploration of unusual and/or novel aromatic structures for various materials applications is described in detail, along with appropriate discussions of relevant structure-property relationships. A brief general introduction to J-aggregates and conjugated polymers is given in Chapter 1, which represents two major areas that are dealt with throughout this thesis. Besides providing an overview of the basic principles, this introductory chapter will hopefully serve to give insight into the motivation behind the work discussed herein. In Chapter 2, the facile one-step construction of highly functionalized cyclohexa-mphenylene macrocycles from simple monobenzenoid building blocks is presented. This methodology is based on a six-fold Suzuki-Miyaura coupling, and represents an improvement over preceding cyclohexa-m-phenylene preparations. In Chapter 3, the development of novel J-aggregating dibenz[aj]anthracene-based macrocycles are reported. These materials are uniquely non-polar compared to all other known Jaggregates, and are also much more photostable relative to the classic J-aggregating cyanine dyes. A variation on the dibenzanthracene theme was extended to the work described in Chapter 4, which features poly(aryleneethynylene)s containing dibenz[a,h]anthracene repeat units. These polymers have unusual stair-stepped structures that confer unto them spectroscopic properties that are atypical of the more common poly(phenyleneethynylene)s. Chapter 5 details recent efforts aimed at utilizing the J-aggregate design principles discussed in Chapter 3 in our search for new J-aggregate candidates in various conjugated polymers and small molecules (e.g. the dibenz[a,m]rubicenes).by Julian M.W. Chan.Ph.D

Scale-invariant magnetic anisotropy in RuCl3_3 at high magnetic fields

In RuCl$_3$, inelastic neutron scattering and Raman spectroscopy reveal a continuum of non-spin-wave excitations that persists to high temperature, suggesting the presence of a spin liquid state on a honeycomb lattice. In the context of the Kitaev model, magnetic fields introduce finite interactions between the elementary excitations, and thus the effects of high magnetic fields - comparable to the spin exchange energy scale - must be explored. Here we report measurements of the magnetotropic coefficient - the second derivative of the free energy with respect to magnetic field orientation - over a wide range of magnetic fields and temperatures. We find that magnetic field and temperature compete to determine the magnetic response in a way that is independent of the large intrinsic exchange interaction energy. This emergent scale-invariant magnetic anisotropy provides evidence for a high degree of exchange frustration that favors the formation of a spin liquid state in RuCl$_3$.Comment: arXiv admin note: substantial text overlap with arXiv:1901.09245. Nature Physic

Weight changes and lifestyle behaviors in women after breast cancer diagnosis: a cross-sectional study

Background: Weight gain rather than weight loss often occurs after breast cancer diagnosis despite breast cancer survivors frequently reported making healthful lifestyle changes. This study describes the prevalence and magnitude of changes in weight before and after breast cancer diagnosis and examines lifestyle behaviors of breast cancer survivors with stable weight, weight gain or weight loss. Methods. Respondents were 368 women with breast cancer characterized by stages I, II and III. All were recruited from hospitals or breast cancer support groups and had completed conventional treatment. Current weight and height were measured while weight at cancer diagnosis and 1 year before diagnosis were self-reported. Weight change was calculated as the difference between current weight and weight a year preceding breast cancer diagnosis. A 24-hour diet recall and Global Physical Activity Questionnaire assessed dietary intake and physical activity, respectively. Differences in lifestyle behaviors among weight change groups were examined using Analysis of Covariance (ANCOVA). Results: Mean weight change from a year preceding diagnosis to study entry was 2.73 kg (95% CI: 1.90-3.55). Most women (63.3%) experienced weight gain rather than weight loss (36.7%) with a higher percentage (47.8%) having at least 5% weight gain (47.8%) rather than weight loss (22%), respectively. Compared to other weight change groups, women in >10% weight gain group had the lowest fruit and vegetable servings (1.58 servings/day; 95% CI: 1.36-1.82) and highest servings of dairy products (0.41 servings/day; 95% CI: 0.30-0.52). Conclusions: Weight gain was evident in this sample of women after breast cancer diagnosis. Information on magnitude of weight change after breast cancer diagnosis and lifestyle behaviors of breast cancer survivors with varying degrees of weight change could facilitate the development and targeting of effective intervention strategies to achieve healthy weight and optimal health for better survival

The UniProt-GO Annotation database in 2011

The GO annotation dataset provided by the UniProt Consortium (GOA: http://www.ebi.ac.uk/GOA) is a comprehensive set of evidenced-based associations between terms from the Gene Ontology resource and UniProtKB proteins. Currently supplying over 100 million annotations to 11 million proteins in more than 360 000 taxa, this resource has increased 2-fold over the last 2 years and has benefited from a wealth of checks to improve annotation correctness and consistency as well as now supplying a greater information content enabled by GO Consortium annotation format developments. Detailed, manual GO annotations obtained from the curation of peer-reviewed papers are directly contributed by all UniProt curators and supplemented with manual and electronic annotations from 36 model organism and domain-focused scientific resources. The inclusion of high-quality, automatic annotation predictions ensures the UniProt GO annotation dataset supplies functional information to a wide range of proteins, including those from poorly characterized, non-model organism species. UniProt GO annotations are freely available in a range of formats accessible by both file downloads and web-based views. In addition, the introduction of a new, normalized file format in 2010 has made for easier handling of the complete UniProt-GOA data set

Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33–40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi ∼900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short ≤20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

European polygenic risk score for prediction of breast cancer shows similar performance in Asian women

Abstract: Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection