Iron Complexes for Photocatalytic Hydrogen Generation

Increasing global energy demands have led to renewed interest in alternative energy sources such as solar power. Devices designed to harness solar power and convert absorbed energy into hydrogen fuel are an attractive option (termed ‘artificial photosynthesis’), and require the development of catalysts for hydrogen generation. We report here a family of iron complexes that are active catalysts for proton reduction to generate H2 gas. Photochemical studies show that ligand modification of the complexes significantly impacts activity levels, and quenching studies elucidate mechanism. These complexes present active, stable, and cost-effective means for hydrogen generation in devices for artificial photosynthesis

Practicing Culturally Competent Therapeutic Jurisprudence: A Collaboration Between Social Work and Law

The Essay will be presented in two parts. Part I lays the theoretical and empirical foundation for the need for an emphasis on lawyers’ cultural competence. Part II then details the substantive content of a culturally competent approach to lawyering. In Part I.A, we define Therapeutic Justice (“TJ”) and discuss some of its current applications. In Part I.B, we identify the commonalities between TJ and the generalist social work model. In Part I.C, we discuss the current thinking and debates on racial and ethnic disparities and discrimination in the criminal justice system from a macro social work perspective. Part I.D describes a TJ approach to lawyering that addresses how TJ might be used to uncover key aspects of racial and ethnic disparities in the legal process. Part I.E presents a discussion of the empirical research that supports the important emphasis on “relationship” in the lawyer-client relationship while arguing that specific attention to racial and ethnic competency is notably missing. In Part II.A, we provide a discussion of the role of race in the lawyer-client relationship using racial identity development theory. Finally, in Part II.B, we present a cultural competency education model that integrates existing approaches in social work and law, and advocates a process that includes recommendations for: institutional change; infusion of diversity content throughout law school curriculum; an exploration of issues of power and oppression; an exploration and challenging of one’s own racial beliefs and biases; and a skill-building component

INVESTIGATIONS OF THE REDOX CHEMISTRY OF COLLOIDAL SEMICONDUCTOR QUANTUM DOTS

Quantum dots (QDs) are quantum-confined, nanometer-size semiconductor crystals that have gained popularity for their optical and charge transfer properties that make them strong candidates in many technologies. Though promising, QD-based device performance typically lags behind their expected potential. Much of this discrepancy is attributed to defects that arise at the QD surface; because of their small size and large surface area to volume ratio, it is established the presence of defects such as undercoordinated surface ions can markedly impact QD properties. Approaches to passivating such defects have been presented such as adding excess ligand or using a core/shell material. However, these efforts are inherently limited by a lack of molecular-level understanding of the QD surface. To address these discrepancies, this dissertation presents studies of QD surface chemistry using a relatively new experimental tool: redox-active chemical probes. Chemical probes are attractive for studying QDs because they can be added stoichiometrically and provide insight into both the structure and reactivity of specific surface sites. Several projects utilizing redox-active probes are presented. First, the reactivity of oleate-capped CdSe QDs with added charge from a radical anion reductant is explored. We present the phenomenon of electron-promoted X-type ligand displacement, an important concept for understanding charge balance at QD surfaces. This concept was then expanded to another QD material: PbS. The influence of parameters including QD size, strength of reductant, and capping ligands are explored in order to gain substantial insight into the factors influencing QD surface defect reactivity. This work moves the field towards new insight into QD surface defects, which will ultimately enable researchers to design rational surface passivation strategies. Finally, a secondary area of research that is critical to advancing QD-based optoelectronic devices is a firmer understanding of the dynamics of interfacial charge transfer from photoexcited QDs. Efforts to develop a system for testing the validity of semiclassical Marcus Theory in interfacial electron transfer between QDs and a molecular acceptor are presented. Realization of this work will help to shape understanding of photoinduced charge transfer in QD-based systems, ultimately helping QD-based devices to reach their full potential.Doctor of Philosoph

Data report of oblique reflection-refraction radio-sonobuoy profiles on the African Atlantic continental margin : (R/V Atlantis II cruises 67 and 75)

Two hundred sixty-four unreversed oblique reflection-refraction profiles using expendable radio-sonobuoys were obtained during two geophysical cruises to the Atlantic continental margin of Africa. This data report gives the profile locations, a summary of the data collection and analysis, and 780 interval reflection and refraction velocities and thicknesses that were determined.Prepared for the International Decade of Ocean Exploration, National Science Foundation Grant GX-28193 for the Eastern Atlantic Continental Margin program

Measurement of H₂O₂ within living drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix

Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is central to mitochondrial oxidative damage and redox signaling, but its roles are poorly understood due to the difficulty of measuring mitochondrial H<sub>2</sub>O<sub>2</sub> in vivo. Here we report a ratiometric mass spectrometry probe approach to assess mitochondrial matrix H<sub>2</sub>O<sub>2</sub> levels in vivo. The probe, MitoB, comprises a triphenylphosphonium (TPP) cation driving its accumulation within mitochondria, conjugated to an arylboronic acid that reacts with H<sub>2</sub>O<sub>2</sub> to form a phenol, MitoP. Quantifying the MitoP/MitoB ratio by liquid chromatography-tandem mass spectrometry enabled measurement of a weighted average of mitochondrial H<sub>2</sub>O<sub>2</sub> that predominantly reports on thoracic muscle mitochondria within living flies. There was an increase in mitochondrial H<sub>2</sub>O<sub>2</sub> with age in flies, which was not coordinately altered by interventions that modulated life span. Our findings provide approaches to investigate mitochondrial ROS in vivo and suggest that while an increase in overall mitochondrial H<sub>2</sub>O<sub>2</sub> correlates with aging, it may not be causative

Electrocatalytic hydrogen evolution by an iron complex containing a nitro-functionalized polypyridyl ligand

Iron polypyridyl complexes have recently been reported to electrocatalytically reduce protons to hydrogen gas at -1.57 V versus Fc(+)/Fc. A new iron catalyst with a nitro-functionalized polypyridyl ligand has been synthesized and found to be active for proton reduction. Interestingly, catalysis occurs at -1.18 V versus Fc(+)/Fc for the nitro-functionalized complex, resulting in an overpotential of 300 mV. Additionally, the complex is active with a turnover frequency of 550 s(-1). Catalysis is also observed in the presence of water with a 12% enhancement in activity. (C) 2015 Elsevier Ltd. All rights reserved

Effect of Depth and Duration of Cooling on Death or Disability at Age 18 Months Among Neonates With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial

Importance Hypothermia for 72 hours at 33.5°C for neonatal hypoxic-ischemic encephalopathy reduces death or disability, but rates continue to be high. Objective To determine if cooling for 120 hours or to a temperature of 32.0°C reduces death or disability at age 18 months in infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants Randomized 2 × 2 factorial clinical trial in neonates (≥36 weeks’ gestation) with hypoxic-ischemic encephalopathy at 18 US centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network between October 2010 and January 2016. Interventions A total of 364 neonates were randomly assigned to 4 hypothermia groups: 33.5°C for 72 hours (n = 95), 32.0°C for 72 hours (n = 90), 33.5°C for 120 hours (n = 96), or 32.0°C for 120 hours (n = 83). Main Outcomes and Measures The primary outcome was death or moderate or severe disability at 18 to 22 months of age adjusted for center and level of encephalopathy. Severe disability included any of Bayley Scales of Infant Development III cognitive score less than 70, Gross Motor Function Classification System (GMFCS) level of 3 to 5, or blindness or hearing loss despite amplification. Moderate disability was defined as a cognitive score of 70 to 84 and either GMFCS level 2, active seizures, or hearing with amplification. Results The trial was stopped for safety and futility in November 2013 after 364 of the planned 726 infants were enrolled. Among 347 infants (95%) with primary outcome data (mean age at follow-up, 20.7 [SD, 3.5] months; 42% female), death or disability occurred in 56 of 176 (31.8%) cooled for 72 hours and 54 of 171 (31.6%) cooled for 120 hours (adjusted risk ratio, 0.92 [95% CI, 0.68-1.25]; adjusted absolute risk difference, −1.0% [95% CI, −10.2% to 8.1%]) and in 59 of 185 (31.9%) cooled to 33.5°C and 51 of 162 (31.5%) cooled to 32.0°C (adjusted risk ratio, 0.92 [95% CI, 0.68-1.26]; adjusted absolute risk difference, −3.1% [95% CI, −12.3% to 6.1%]). A significant interaction between longer and deeper cooling was observed (P = .048), with primary outcome rates of 29.3% at 33.5°C for 72 hours, 34.5% at 32.0°C for 72 hours, 34.4% at 33.5°C for 120 hours, and 28.2% at 32.0°C for 120 hours. Conclusions and Relevance Among term neonates with moderate or severe hypoxic-ischemic encephalopathy, cooling for longer than 72 hours, cooling to lower than 33.5°C, or both did not reduce death or moderate or severe disability at 18 months of age. However, the trial may be underpowered, and an interaction was found between longer and deeper cooling. These results support the current regimen of cooling for 72 hours at 33.5°C

A High-Throughput Platform for Lentiviral Overexpression Screening of the Human ORFeome

In response to the growing need for functional analysis of the human genome, we have developed a platform for high-throughput functional screening of genes overexpressed from lentiviral vectors. Protein-coding human open reading frames (ORFs) from the Mammalian Gene Collection were transferred into lentiviral expression vector using the highly efficient Gateway recombination cloning. Target ORFs were inserted into the vector downstream of a constitutive promoter and upstream of an IRES controlled GFP reporter, so that their transfection, transduction and expression could be monitored by fluorescence. The expression plasmids and viral packaging plasmids were combined and transfected into 293T cells to produce virus, which was then used to transduce the screening cell line. We have optimised the transfection and transduction procedures so that they can be performed using robotic liquid handling systems in arrayed 96-well microplate, one-gene-per-well format, without the need to concentrate the viral supernatant. Since lentiviruses can infect both dividing and non-dividing cells, this system can be used to overexpress human ORFs in a broad spectrum of experimental contexts. We tested the platform in a 1990 gene pilot screen for genes that can increase proliferation of the non-tumorigenic mammary epithelial cell line MCF-10A after removal of growth factors. Transduced cells were labelled with the nucleoside analogue 5-ethynyl-2′-deoxyuridine (EdU) to detect cells progressing through S phase. Hits were identified using high-content imaging and statistical analysis and confirmed with vectors using two different promoters (CMV and EF1α). The screen demonstrates the reliability, versatility and utility of our screening platform, and identifies novel cell cycle/proliferative activities for a number of genes

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

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