Thermal and other tests of photovoltaic modules performed in natural sunlight

The bulk of the testing was the characterization of twenty-nine modules according to their nominal operating cell temperature (NOCT) and the effect on NOCT of changes in module design, various residential roof mounting configurations, and dirt accumulation. Other tests, often performed parallel with the NOCT measurements, evaluated the improvement in electrical performance by cooling the modules with water and by channeling the waste heat into a phase change material (wax). Electrical degradation resulting from the natural marriage of photovoltaic and solar water heating modules was also demonstrated. Cost effectiveness of each of these techniques are evaluated in light of the LSA cost goal of $0.50 per watt

Fences and Gates: A Survey of Collaborative Aspects of District Court Practice in Light of Self-Represented Litigants, Addiction, and the Mandate to Formulate Plans

The district courts of North Carolina are called to handle a multitude of legal issues, many of which are vital, personal issues facing individuals in our society. Court dockets swell with cases for resolution, due in part to substance use disorder, addiction, and legal issues that frequently arise as a result of them. The court must adjudicate in the midst of these complex challenges experienced by the litigants. These litigants are also increasingly appearing before the court without legal counsel. In Reinventing the Courts: The Frontiers of Judicial Activism in the State Courts, criticism is leveled at courts that attempt to solve these problems. Under legislative direction and ethical duty, a North Carolina district court judge may utilize collaborative and problem-solving methods to bring cases to a resolution. These methods, despite the criticism of Frontiers, are not far beyond the historically contemplated purposes of courts and are well within long-standing structural safeguards, statutory requirements and ethical obligations. In many instances, the court is called to resolve these issues and formulate plans for resolution of these cases by the North Carolina General Assembly. The challenges that present in court everyday often need these approved, prescribed problem solving approaches to answer the needs of the litigants

Methods for Scarless, Selection-Free Generation of Human Cells and Allele-Specific Functional Analysis of Disease-Associated SNPs and Variants of Uncertain Significance.

With the continued emergence of risk loci from Genome-Wide Association studies and variants of uncertain significance identified from patient sequencing, better methods are required to translate these human genetic findings into improvements in public health. Here we combine CRISPR/Cas9 gene editing with an innovative high-throughput genotyping pipeline utilizing KASP (Kompetitive Allele-Specific PCR) genotyping technology to create scarless isogenic cell models of cancer variants in ~1 month. We successfully modeled two novel variants previously identified by our lab in the PALB2 gene in HEK239 cells, resulting in isogenic cells representing all three genotypes for both variants. We also modeled a known functional risk SNP of colorectal cancer, rs6983267, in HCT-116 cells. Cells with extremely low levels of gene editing could still be identified and isolated using this approach. We also introduce a novel molecular assay, ChIPnQASO (Chromatin Immunoprecipitation and Quantitative Allele-Specific Occupation), which uses the same technology to reveal allele-specific function of these variants at the DNA-protein interaction level. We demonstrated preferential binding of the transcription factor TCF7L2 to the rs6983267 risk allele over the non-risk. Our pipeline provides a platform for functional variant discovery and validation that is accessible and broadly applicable for the progression of efforts towards precision medicine

A Structure-free Method for Quantifying Conformational Flexibility in proteins

All proteins sample a range of conformations at physiologic temperatures and this inherent flexibility enables them to carry out their prescribed functions. A comprehensive understanding of protein function therefore entails a characterization of protein flexibility. Here we describe a novel approach for quantifying a protein’s flexibility in solution using small-angle X-ray scattering (SAXS) data. The method calculates an effective entropy that quantifies the diversity of radii of gyration that a protein can adopt in solution and does not require the explicit generation of structural ensembles to garner insights into protein flexibility. Application of this structure-free approach to over 200 experimental datasets demonstrates that the methodology can quantify a protein’s disorder as well as the effects of ligand binding on protein flexibility. Such quantitative descriptions of protein flexibility form the basis of a rigorous taxonomy for the description and classification of protein structure.Massachusetts Institute of Technology (Steve G. and Renee Finn Faculty Innovation Fellowship)Swiss National Science Foundation (Early Postdoc.Mobility Fellowship

Residual Spiritual Shifts Regarding the Homeless Resulting From a College Poverty Immersion Experience

We report the results of a qualitative study, having interviewed 20 students who had 1.5 years previously been involved in a collegiate, weekend poverty immersion experience. We coded the transcripts, analyzed the data from a phenomenological framework, provided checks for internal validity, and report the common themes from the participants’ interviews.Three overall results were evident. First, participants reported believing that, generally, the church is ignorant regarding the needs of the poor and impoverished people around them. Second, students generally did not believe that the church was doing enough in order to combat poverty and/or homelessness, mentioning that the church’s outreach ministries are often ineffective. Third, students reported believing that the church is responsible to care for the poor and thus, Christians as a whole should be more involved than they are presently. The study’s results are discussed in the context of social psychology findings, published research literature reading how contemporary Christians generally fare at helping impoverished individuals, and the long term effectiveness of active, experiential learning in higher education

Motif Discovery in Physiological Datasets: A Methodology for Inferring Predictive Elements

In this article, we propose a methodology for identifying predictive physiological patterns in the absence of prior knowledge. We use the principle of conservation to identify activity that consistently precedes an outcome in patients, and describe a two-stage process that allows us to efficiently search for such patterns in large datasets. This involves first transforming continuous physiological signals from patients into symbolic sequences, and then searching for patterns in these reduced representations that are strongly associated with an outcome. Our strategy of identifying conserved activity that is unlikely to have occurred purely by chance in symbolic data is analogous to the discovery of regulatory motifs in genomic datasets. We build upon existing work in this area, generalizing the notion of a regulatory motif and enhancing current techniques to operate robustly on non-genomic data. We also address two significant considerations associated with motif discovery in general: computational efficiency and robustness in the presence of degeneracy and noise. To deal with these issues, we introduce the concept of active regions and new subset-based techniques such as a two-layer Gibbs sampling algorithm. These extensions allow for a framework for information inference, where precursors are identified as approximately conserved activity of arbitrary complexity preceding multiple occurrences of an event. We evaluated our solution on a population of patients who experienced sudden cardiac death and attempted to discover electrocardiographic activity that may be associated with the endpoint of death. To assess the predictive patterns discovered, we compared likelihood scores for motifs in the sudden death population against control populations of normal individuals and those with non-fatal supraventricular arrhythmias. Our results suggest that predictive motif discovery may be able to identify clinically relevant information even in the absence of significant prior knowledge.CIMIT: Center for Integration of Medicine and Innovative TechnologyHarvard University--MIT Division of Health Sciences and Technolog

Haplotype analysis of the internationally distributed BRCA1 c.3331_3334delCAAG founder mutation reveals a common ancestral origin in Iberia

BACKGROUND: The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. METHODS: BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. RESULTS: The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period. CONCLUSIONS: Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening

Hidden States within Disordered Regions of the CcdA Antitoxin Protein

The bacterial toxin–antitoxin system CcdB–CcdA provides a mechanism for the control of cell death and quiescence. The antitoxin protein CcdA is a homodimer composed of two monomers that each contain a folded N-terminal region and an intrinsically disordered C-terminal arm. Binding of the intrinsically disordered C-terminal arm of CcdA to the toxin CcdB prevents CcdB from inhibiting DNA gyrase and thereby averts cell death. Accurate models of the unfolded state of the partially disordered CcdA antitoxin can therefore provide insight into general mechanisms whereby protein disorder regulates events that are crucial to cell survival. Previous structural studies were able to model only two of three distinct structural states, a closed state and an open state, that are adopted by the C-terminal arm of CcdA. Using a combination of free energy simulations, single-pair Förster resonance energy transfer experiments, and existing NMR data, we developed structural models for all three states of the protein. Contrary to prior studies, we find that CcdA samples a previously unknown state where only one of the disordered C-terminal arms makes extensive contacts with the folded N-terminal domain. Moreover, our data suggest that previously unobserved conformational states play a role in regulating antitoxin concentrations and the activity of CcdA’s cognate toxin. These data demonstrate that intrinsic disorder in CcdA provides a mechanism for regulating cell fate