TiO2/PDMS Buoyant Photocatalyst for Water Remediation and Cu‑RBS Organic/Inorganic Hybrid for Thermoelectric Applications

Two novel materials have been developed: TiO2/poly(dimethylsiloxane) (PDMS) beads as buoyant photocatalyst materials for water remediation, and copper rhodamine‑B silane (Cu‑RBS) as an n ‑type organic/inorganic hybrid for thermoelectric applications. The approach to incorporate TiO2 into low‑density PDMS beads addresses many of the challenges traditionally encountered when creating buoyant photocatalysts, an area which is crucial for wide‑spread remediation of water resources, including natural bodies of water. The performance and reusability of the buoyant photocatalyst materials, demonstrated by using methylene blue as a model degradation target, is strong enough for environmental application. The use of a kinetic model and the introduction of a parameter to allow comparison of buoyant photocatalysts is also included as part of the analysis. The performance of Cu‑RBS was investigated as a low‑temperature thermoelectric material. Clear improvements in the electrical conductivity and Seebeck coefficient are observed for RBS upon coordination to Cu2+. Evidence explaining this improvement is provided by computational analysis and by concentration‑dependent optical absorption and fluorescent emission measurements, all of which indicate that a metal‑to‑ligand charge transfer occurs from Cu2+ to RBS. Although the power factor of Cu‑RBS is low compared to other materials reported in the literature, these results provide a promising approach to increasing both the Seebeck coefficient and electrical conductivity of n‑type small molecule organic systems

TREX1 is expressed by microglia in normal human brain and increases in regions affected by ischemia

BACKGROUND: Mutations in the three-prime repair exonuclease 1 (TREX1) gene have been associated with neurological diseases, including Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). However, the endogenous expression of TREX1 in human brain has not been studied. METHODS: We produced a rabbit polyclonal antibody (pAb) to TREX1 to characterize TREX1 by Western blotting (WB) of cell lysates from normal controls and subjects carrying an RVCL frame-shift mutation. Dual staining was performed to determine cell types expressing TREX1 in human brain tissue. TREX1 distribution in human brain was further evaluated by immunohistochemical analyses of formalin-fixed, paraffin-embedded samples from normal controls and patients with RVCL and ischemic stroke. RESULTS: After validating the specificity of our anti-TREX1 rabbit pAb, WB analysis was utilized to detect the endogenous wild-type and frame-shift mutant of TREX1 in cell lysates. Dual staining in human brain tissues from patients with RVCL and normal controls localized TREX1 to a subset of microglia and macrophages. Quantification of immunohistochemical staining of the cerebral cortex revealed that TREX1 CONCLUSIONS: TREX1 is expressed by a subset of microglia in normal human brain, often in close proximity to the microvasculature, and increases in the setting of ischemic lesions. These findings suggest a role for TREX

The burden of proof: the current state of atrial fibrillation prevention and treatment trials

Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3–5, 2015

Tumor Response to Radiotherapy is Dependent on Genotype-Associated Mechanisms in vitro and in vivo

Background: We have previously shown that in vitro radiosensitivity of human tumor cells segregate non-randomly into a limited number of groups. Each group associates with a specific genotype. However we have also shown that abrogation of a single gene (p21) in a human tumor cell unexpectedly sensitized xenograft tumors comprised of these cells to radiotherapy while not affecting in vitro cellular radiosensitivity. Therefore in vitro assays alone cannot predict tumor response to radiotherapy. In the current work, we measure in vitro radiosensitivity and in vivo response of their xenograft tumors in a series of human tumor lines that represent the range of radiosensitivity observed in human tumor cells. We also measure response of their xenograft tumors to different radiotherapy protocols. We reduce these data into a simple analytical structure that defines the relationship between tumor response and total dose based on two coefficients that are specific to tumor cell genotype, fraction size and total dose. Methods: We assayed in vitro survival patterns in eight tumor cell lines that vary in cellular radiosensitivity and genotype. We also measured response of their xenograft tumors to four radiotherapy protocols: 8 × 2 Gy; 2 × 5Gy, 1 × 7.5 Gy and 1 × 15 Gy. We analyze these data to derive coefficients that describe both in vitro and in vivo responses. Results: Response of xenografts comprised of human tumor cells to different radiotherapy protocols can be reduced to only two coefficients that represent 1) total cells killed as measured in vitro 2) additional response in vivo not predicted by cell killing. These coefficients segregate with specific genotypes including those most frequently observed in human tumors in the clinic. Coefficients that describe in vitro and in vivo mechanisms can predict tumor response to any radiation protocol based on tumor cell genotype, fraction-size and total dose. Conclusions: We establish an analytical structure that predicts tumor response to radiotherapy based on coefficients that represent in vitro and in vivo responses. Both coefficients are dependent on tumor cell genotype and fraction-size. We identify a novel previously unreported mechanism that sensitizes tumors in vivo; this sensitization varies with tumor cell genotype and fraction size

Nanorg Microbial Factories: Light-Driven Renewable Biochemical Synthesis Using Quantum Dot-Bacteria Nanobiohybrids

Living cells do not interface naturally with nanoscale materials, although such artificial organisms can have unprecedented multifunctional properties, like wireless activation of enzyme function using electromagnetic stimuli. Realizing such interfacing in a nanobiohybrid organism (or nanorg) requires (1) chemical coupling via affinity binding and self-assembly, (2) the energetic coupling between optoelectronic states of artificial materials with the cellular process, and (3) the design of appropriate interfaces ensuring biocompatibility. Here we show that seven different core−shell quantum dots (QDs), with excitations ranging from ultraviolet to near-infrared energies, couple with targeted enzyme sites in bacteria. When illuminated by light, these QDs drive the renewable production of different biofuels and chemicals using carbon-dioxide (CO2), water, and nitrogen (from air) as substrates. These QDs use their zinc-rich shell facets for affinity attachment to the proteins. Cysteine zwitterion ligands enable uptake through the cell, facilitating cell survival. Together, these nanorgs catalyze light-induced air−water−CO2 reduction with a high turnover number (TON) of ∼106-108 (mols of product per mol of cells) to biofuels like isopropanol (IPA), 2,3-butanediol (BDO), C11−C15 methyl ketones (MKs), and hydrogen (H2); and chemicals such as formic acid (FA), ammonia (NH3), ethylene (C2H4), and degradable bioplastics polyhydroxybutyrate (PHB). Therefore, these resting cells function as nanomicrobial factories powered by light

802-6 The Cost-Effectiveness of Pravastatin in Secondary Prevention of Coronary Heart Disease

To determine the cost-effectiveness of pravastatin therapy in patients with coronary heart disease, a projected risk model was developed that used the results of the three-year, double blind, placebo controlled clinical trials: Pravastatin Limitation ofAtherosclerosis in the Coronary Arteries (PLAC I) and Pravastatin, Upids and Atherosclerosis in the Carotid Arteries (PLAC II). In addition to measuring atherosclerotic progression, the PLAC studies evaluated four outcome variables: coronary heart disease death, non-coronary heart disease death, fatal myocardial infarction, and non-fatal myocardial infarction in a patient population (mean age 60 years) with established coronary heart disease and moderate low-density-lipoprotein cholesterol levels, Pooled PLAC data analysis (n=559) revealed a statistically significant (p<0.05) difference in male non-fatal myocardial infarctions between the pravastatin and placebo groups. The projected risk model utilized Framingham data to project the risk of mortality 10 years post myocardial infarction. Markov Process was used to estimate the life-years saved and cost. All costs and benefits were discounted by 5%, Results are presented in the table below:Patient Risk ProfileCost per Life-Year SavedMale with CHD + 1Additional Risk Factor$19,082Male with CHD + 2 Additional Risk Factors$14,022Male with CHD + 3 Additional Risk Factors$10,630Based on this model, pravastatin monotherapy in secondary prevention of coronary heart disease has a cost-effectiveness ratio comparable to some of the widely accepted medical interventions such as breast cancer screening,$21,700, hydrochlorothiazide in the treatment of hypertension, $16,400, and pneumococcal vaccine,$12,000

Bell Inequality Experiment for a High Brightness Time-Energy Entangled Source

A periodically poled MgO - doped LiNbO3 (MgO:LN) non-degenerate photon pair source is utilized for spontaneous parametric down-conversion of 532-nanometer photons into time-energy entangled pairs of 800- and 1600-nanometer photons. The entangled photons are separated using previously detailed sorting optics, such that each wavelength is independently directed through one of two modified Mach-Zehnder interferometers - also known as a Franson interferometer - after which they are fiber-optically guided to high-efficiency photon detectors. Output from the detectors is sent to a high resolution time tagger, where coincidences between the entangled photons are recorded. By varying the length of the long path in one Mach-Zehnder interferometer, it is possible to observe high visibility sinusoidal fringes in the measured coincidence rates (while no variation is seen in single photon detection rates). These fringes - due to interference between the photon probability amplitudes - are indicative of a violation of the Bell inequality, and confirm inconsistencies with local hidden variable theory for the correlations of the time-energy entangled photon pairs

Bell Inequality Experiment for a High Brightness Time-Energy Entangled Source

A periodically poled MgO doped LiNbO3 (MgO:LN) non-degenerate photon pair source is utilized for spontaneous parametric down-conversion of 532 nm photons into time-energy entangled pairs of 800 and 1600 nm photons. The entangled photons are separated using previously detailed sorting optics, such that each wavelength is independently directed through one of two modified Mach-Zehnder interferometers also known as a Franson interferometer after which they are fiber-optically guided to high-efficiency photon detectors. Output from the detectors is sent to a high resolution time tagger, where coincidences between the entangled photons are recorded. By varying the length of the long path in one Mach-Zehnder interferometer, it is possible to observe high visibility sinusoidal fringes in the measured coincidence rates (while no variation is seen in single photon detection rates). These fringes due to interference between the photon probability amplitudes are indicative of a violation of the Bell inequality, and confirm inconsistencies with local hidden variable theory for the correlations of the time-energy entangled photon pairs

Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants

BACKGROUND During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation. METHODS Kidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24h after birth. Using image analysis, nephrogenic zone width, the number of glomerular generations, renal corpuscle cross-sectional area and the cellular composition of glomeruli were examined. Kidneys from female and male infants were analysed separately. FINDINGS The number of glomerular generations formed within the fetal kidneys was directly proportional to gestational age, body weight and kidney weight, with variability between individuals in the ultimate number of generations (8 to 12) and in the timing of the cessation of nephrogenesis (still ongoing at 37weeks gestation in one infant). There was a slight but significant (r2=0.30, P=0.001) increase in renal corpuscle cross-sectional area from mid gestation to term in females, but this was not evident in males. The proportions of podocytes, endothelial and non-epithelial cells within mature glomeruli were stable throughout gestation. INTERPRETATION These findings highlight spatial and temporal variability in nephrogenesis in the developing human kidney, whereas the relative cellular composition of glomeruli does not appear to be influenced by gestational age.This study was supported by funding from the National Health and Medical Research Council (NHMRC) (1011136) of Australia and National Institutes of Health (NIH) USA grant 3U01DK094526-04S1 (PI A P McMahon). Author Danica Ryan was the recipient of the Biomedicine Discovery Scholarship from Monash University and author Megan R. Sutherland was supported by a NHMRC CJ Martin Fellowship