Aggregation of Charge Acceptors on Nanocrystal Surfaces Alters Rates of Photoinduced Electron Transfer.

Semiconductor nanocrystals (NCs) interfaced with molecular ligands that function as charge and energy acceptors are an emerging platform for the design of light-harvesting, photon-upconverting, and photocatalytic materials. However, NC systems explored for these applications often feature high concentrations of bound acceptor ligands, which can lead to ligand-ligand interactions that may alter each system's ability to undergo charge and energy transfer. Here, we demonstrate that aggregation of acceptor ligands impacts the rate of photoinduced NC-to-ligand charge transfer between lead(II) sulfide (PbS) NCs and perylenediimide (PDI) electron acceptors. As the concentration of PDI acceptors is increased, we find the average electron transfer rate from PbS to PDI ligands decreases by nearly an order of magnitude. The electron transfer rate slowdown with increasing PDI concentration correlates strongly with the appearance of PDI aggregates in steady-state absorption spectra. Electronic structure calculations and molecular dynamics (MD) simulations suggest PDI aggregation slows the rate of electron transfer by reducing orbital overlap between PbS charge donors and PDI charge acceptors. While we find aggregation slows electron transfer in this system, the computational models we employ predict ligand aggregation could also be used to speed electron transfer by producing delocalized states that exhibit improved NC-molecule electronic coupling and energy alignment with NC conduction band states. Our results demonstrate that ligand aggregation can alter rates of photoinduced electron transfer between NCs and organic acceptor ligands and should be considered when designing hybrid NC:molecule systems for charge separation.

Evaluating the Effect of Dye-Dye Interactions of Xanthene-Based Fluorophores in the Fluorosequencing of Peptides.

A peptide sequencing scheme utilizing fluorescence microscopy and Edman degradation to determine the amino acid position in fluorophore-labeled peptides was recently reported, referred to as fluorosequencing. It was observed that multiple fluorophores covalently linked to a peptide scaffold resulted in a decrease in the anticipated fluorescence output and worsened the single-molecule fluorescence analysis. In this study, we report an improvement in the photophysical properties of fluorophore-labeled peptides by incorporating long and flexible (PEG)10 linkers at the peptide attachment points. Long linkers to the fluorophores were installed using copper-catalyzed azide-alkyne cycloaddition conditions. The photophysical properties of these peptides were analyzed in solution and immobilized on a microscope slide at the single-molecule level under peptide fluorosequencing conditions. Solution-phase fluorescence analysis showed improvements in both quantum yield and fluorescence lifetime with the long linkers. While on the solid support, photometry measurements showed significant increases in fluorescence brightness and 20 to 60% improvements in the ability to determine the amino acid position with fluorosequencing. This spatial distancing strategy demonstrates improvements in the peptide sequencing platform and provides a general approach for improving the photophysical properties in fluorophore-labeled macromolecules.

Mechanistic Analysis of Solid-State Colorimetric Switching: Monoalkoxynaphthalene-Naphthalimide Donor-Acceptor Dyads.

There is growing interest in creating solids that are responsive to various stimuli. Herein we report the first molecular-level mechanistic picture of the thermochromic polymorphic transition in a series of MAN-NI dyad crystals that turn from orange to yellow upon heating with minimal changes to the microscopic morphology following the transition. Detailed structural analyses revealed that the dyads assemble to create an alternating bilayer type structure, with horizontal alternating alkyl and stacked aromatic layers in both the orange and yellow forms. The observed dynamic behavior in the solid state moves as a yellow wavefront through the orange crystal. The overall process is critically dependent on a complex interplay between the layered structure of the starting crystal, the thermodynamics of the two differently colored forms, and similar densities of the two polymorphs. Upon heating, the orange form alkyl chain layers become disordered, allowing for some lateral diffusion of dyads within their own layer. Moving to either adjacent stack in the same layer allows a dyad to exchange a head-to-head stacking geometry (orange) for a head-to-tail stacking geometry (yellow). This transition is unique in that it involves a nucleation and growth mechanism that converts to a faster cooperative wavefront mechanism during the transition. The fastest moving of the wavefronts have an approximately 38° angle with respect to the long axis of the crystal, corresponding to a nonconventional C-H···O hydrogen bond network of dyad molecules in adjacent stacks that enables a transition with cooperative character to proceed within layers of orange crystals. The orange-to-yellow transition is triggered at a temperature that is very close to the temperature at which the orange and yellow forms exchange as the more stable, while being lower than the melting temperature of the original orange, or final yellow, solids.

Pesticide removal through wastewater and advanced treatment: full-scale sampling and bench-scale testing.

Dieldrin and DDx removal through wastewater treatment, ozonation, and microfiltration was assessed for a water reuse project for groundwater replenishment in Monterey, California, USA. Full-scale sampling was conducted at the wastewater treatment plant, and physical wastewater treatment processes, ozonation, and microfiltration were tested at the bench scale. Removals observed through wastewater treatment, ozonation, and microfiltration were 84%, 44% to 63%, and 97% to 98%, respectively, for dieldrin, and 93%, 36% to 48%, and 92% to 94% for DDx. These were sufficient to meet California Ocean Plan water quality objectives after wastewater treatment alone. Levels in the secondary effluent, ahead of ozonation, microfiltration, reverse osmosis and advanced oxidation in the advanced water purification facility, met drinking water standards. Removal of dieldrin and DDx through wastewater treatment occurred by physical treatment processes; removal through the full-scale wastewater treatment plant, which included biological and physical treatment processes, matched removal through the physical bench-scale wastewater treatment processes. Dieldrin and DDx removal correlated with removal of volatile suspended solids, suggesting that volatile suspended solids could be used as an indicator for pesticide removal through wastewater treatment. Dieldrin and DDx concentrations were highest in the solids contact process, where biomass is accumulated for carbon removal.

Age-related reductions in whole brain mass and telencephalon volume in very old white Carneau pigeons (Columba livia).

While studies have identified age-related cognitive impairment in pigeons (Columba livia), no study has detected the brain atrophy which typically accompanies cognitive impairment in older mammals. Instead, Coppola and Bingman (Aging is associated with larger brain mass and volume in homing pigeons (Columba livia), Neurosci. Letters 698 (2019) 39-43) reported increased whole brain mass and telencephalon volume in older, compared to younger, homing pigeons. One reason for this unexpected finding might be that the older pigeons studied were not old enough to display age-related brain atrophy. Therefore, the current study repeated Coppola and Bingman, but with a sample of older white Carneau pigeons that were on average 5.34 years older. Brains from young and old homing pigeons were weighed and orthogonal measurements of the telencephalon, cerebellum, and optic tectum were obtained. Despite having a heavier body mass than younger pigeons, older pigeons had a significant reduction in whole brain mass and telencephalon volume, but not cerebellum or optic tectum volume. This study is therefore the first to find that pigeons experience age-related brain atrophy.

Primary peritonitis due to group A Streptococcus in a previously healthy pediatric patient.

Primary peritonitis remains a rare disease in otherwise healthy children, with group A Streptococcus (GAS) being a particularly unusual cause. A case involving a 14-year-old girl, who presented with an 'acute abdomen' and was taken to the operating room for urgent laparoscopy, is reported. Abdominal and pelvic structures were only minimally inflamed, as was the appendix. Peritoneal fluid and blood cultures both grew pure cultures of GAS. The patient's course was complicated by streptococcal toxic shock syndrome. She fortunately made a full recovery. The present report highlights the diagnostic and treatment dilemmas associated with GAS primary peritonitis.

La péritonite primaire demeure une maladie rare chez un enfant autrement en santé, et le streptocoque du groupe A (SGA) en est une cause particulièrement inhabituelle. Les auteurs présentent le cas d'une fille de 14 ans qui a consulté en raison d'un « abdomen aigu ¼ et a dû subir une laparoscopie d'urgence en salle d'opération. Les structures abdominale et pelvienne, de même que l'appendice, étaient peu enflammées. Le liquide péritonéal et les prélèvements sanguins ont tous deux permis d'obtenir des cultures pures de SGA. L'évolution de la patiente a été compliquée par un syndrome de choc toxique streptococcique. Heureusement, elle s'est entièrement rétablie. Le présent rapport souligne les dilemmes diagnostiques et thérapeutiques associés à la péritonite primaire à SGA.

Evaluation of a method to measure fluorescent cell burden in complex culture systems.

Purpose. This work introduces and evaluates a method for accurate in-vitro measurement of fluorescent cell burden in complex 3D-culture conditions.Methods.The Fluorescent Cell Burden (FCB) method was developed to analyze the burden of 4T1 mCherry-expressing cells grown in an organotypic co-culture model of brain metastasis using 400µm rat brain slices. As a first step, representative simulated image-data accurately reflecting the 4T1 experimental data, but with known ground truth burden, were created. The FCB method was then developed in the CellProfiler software to measure the integrated intensity and area of the colonies in the simulated image data. Parameters in the pipeline were varied to span the experimentally observed range (e.g. of cell colony size) and the result compared with simulation ground truth to evaluate and optimize FCB performance. The optimized CellProfiler pipeline was then applied to the original 4T1 tumor cell images to determine colony growth with time, and re-applied with upper and lower bound parameters to determine uncertainty estimates.Results.The FCB method measured integrated intensity across 10 simulated images with an accuracy of 99.23% ± 0.75%. When colony density was increased by increasing colony number to 450, 600, and 750, the FCB measurement was 98.68%, 100.9%, 97.6% and 113.5% of the true value respectively. For the increasing number of cells plated on the rat brain slices, the integrated intensity increased nearly linearly with cell count except for at high cell counts, where it is hypothesized that shadowing from clumped cells causes a sub-linear relationship.Conclusion. The FCB method accurately measured an integrated fluorescent light intensity to within 5% of ground truth for a wide range of simulated image data spanning the range of observed variability in experimental data. The method is readily customizable to in-vitro studies requiring estimation of fluorescent tumor cell burden.

Using Spectator Ligands to Enhance Nanocrystal-to-Molecule Electron Transfer.

Semiconductor nanocrystals (NCs) have emerged as promising photocatalysts. However, NCs are often functionalized with complex ligand shells that contain not only charge acceptors but also other "spectator ligands" that control NC solubility and affinity for target reactants. Here, we show that spectator ligands are not passive observers of photoinduced charge transfer but rather play an active role in this process. We find the rate of electron transfer from quantum-confined PbS NCs to perylenediimide acceptors can be varied by over a factor of 4 simply by coordinating cinnamate ligands with distinct dipole moments to NC surfaces. Theoretical calculations indicate this rate variation stems from both ligand-induced changes in the free energy for charge transfer and electrostatic interactions that alter perylenediimide electron acceptor orientation on NC surfaces. Our work shows NC-to-molecule charge transfer can be fine-tuned through ligand shell design, giving researchers an additional handle for enhancing NC photocatalysis.

Centralised urban stormwater harvesting for potable reuse.

Urban impervious areas provide a guaranteed source of runoff, especially in cities with high rainfall - this represents a source of water with low sensitivity to unfavourable climate change. Whilst the potential to reuse stormwater has long been recognised, its quality has largely limited usage to non-potable applications requiring the use of a third-pipe network, a prohibitively expensive option in established urban areas. Given recent advances in membrane filtration, this study investigates the potential of harvesting and treating stormwater to a potable standard to enable use of the potable distribution network. A case study based on the Throsby Creek catchment in Newcastle explores the issue. The high seasonally uniform rainfall provides insight into the maximum potential of such an option. Multicriterion optimisation was used to identify Pareto optimal solutions for harvesting, storing and treating stormwater. It is shown that harvesting and treating stormwater from a 13 km² catchment can produce yields ranging from 8.5 to 14.2 ML/day at costs ranging from AU$2.60/kL to AU$2.89/kL, which may become viable as the cost of traditional supply continues to grow. However, there are significant social impacts to deal with including alienation of public land for storage and community acceptance of treated stormwater.

Combination of two analytical techniques improves wine classification by Vineyard, Region, and vintage.

Three important wine parameters: vineyard, region, and vintage year, were evaluated using fifteen Vitis vinifera L. 'Pinot noir' wines derived from the same scion clone (Pinot noir 667). These wines were produced from two vintage years (2015 and 2016) and eight different regions along the Pacific Coast of the United States. We successfully improved the classification of the selected Pinot noir wines by combining an untargeted 1D 1H NMR analysis with a targeted peptide based differential sensing array. NMR spectroscopy was used to evaluate the chemical fingerprint of the wines, whereas the peptide-based sensing array is known to mimic the senses of taste, smell, and palate texture by characterizing the phenolic profile. Multivariate and univariate statistical analyses of the combined NMR and differential sensing array dataset classified the genetically identical Pinot noir wines on the basis of distinctive metabolic signatures associated with the region of growth, vineyard, and vintage year.

The centrosome in neuronal development.

Establishment of polarity is an essential process during proliferation, migration and differentiation in neurons, and the signaling pathways leading to polarization of the cytoskeleton are topics of intense research. One key marker for cell polarity is the centrosome, also known as the microtubule-organizing center. Recent discoveries have shown that the position of the centrosome is precisely regulated during neurogenesis, migration and differentiation, leading to the segregation of cell fate factors, efficient nucleokinesis and directed neurite outgrowth, respectively. Here, we review recent advances in the understanding of this interesting organelle and propose a model whereby centrosome position, determined by extracellular factors, directs multiple aspects of neuronal development.

Translating Research into Agile Development (TRIAD): Development of Electronic Health Record Tools for Primary Care Settings.

OBJECTIVES: This article describes a method for developing electronic health record (EHR) tools for use in primary care settings. METHODS: The "Translating Research into Agile Development" (TRIAD) method relies on the close collaboration of researchers, end users, and development teams. This five-step method for designing a tailored EHR tool includes (1) assessment, observation, and documentation; (2) structured engagement for collaboration and iterative data collection; (3) data distillation; (4) developmental feedback from clinical team members on high-priority EHR needs and input on design prototypes and EHR functionality; and (5) agile scrum sprint cycles for prototype development. RESULTS: The TRIAD method was used to modify an existing EHR for behavioral health clinicians (BHCs) embedded with primary care teams, called the BH e-Suite. The structured engagement processes stimulated discussions on how best to automate BHC screening tools and provide goal tracking functionality over time. Data distillation procedures rendered technical documents, with information on workflow steps, tasks, and associated challenges. In the developmental feedback phase, BHCs gave input on screening assessments, scoring needs, and other functionality to inform prototype feature development. Six 2-week sprint cycles were conducted to address three domains of prototype development: assessment and documentation needs, information retrieval, and monitoring and tracking. The BH e-Suite tool resulted with eight new EHR features to accommodate BHCs' needs. CONCLUSION: The TRIAD method can be used to develop EHR functionality to address the evolving needs of health professionals in primary care and other settings. The BH e-Suite was developed through TRIAD and was found to be acceptable, easy to use, and improved care delivery during pilot testing. The BH e-Suite was later adopted by OCHIN Inc., which provided the tool to its 640 community health centers. This suggests that the TRIAD method is a promising research and development approach.

Health care clinicians' engagement in organizational redesign of care processes: The importance of work and organizational conditions.

The Swedish health care system is reorienting towards horizontal organization for care processes. A main challenge is to engage health care clinicians in the process. The aim of this study was to assess engagement (i.e. attitudes and beliefs, the cognitive state and clinical engagement behaviour) among health care clinicians, and to investigate how engagement was related to work resources and demands during organizational redesign. A cohort study was conducted, using a questionnaire distributed to clinicians at five hospitals working with care process improvement approaches, two of them having implemented Lean production. The results show that kinds of engagement are interlinked and contribute to clinical engagement behaviour in quality of care and patient safety. Increased work resources have importance for engagements in organizational improvements, especially in top-down implementations. An extended work engagement model during organizational improvements in health care was supported. The model contributes to knowledge about how and when clinicians are mobilized to engage in organizational changes.

Pulmonary scintigraphy in fibrosing mediastinitis due to histoplasmosis.

The pulmonary scintigraphic findings from four patients with fibrosing mediastinitis due to histoplasmosis are reported. The ventilation/perfusion (V/Q) mismatch mimicked pulmonary emboli. However, in these cases the chest radiographs and/or gallium-67 scintigraphy were abnormal, suggesting mediastinal or hilar disease. Awareness of the nonembolic conditions that can result in V/Q mismatches is important in the interpretation of lung scans.

Pathways to improved radiologic research. An NIH workshop.

In summary, the workshop recommended two years of research training as being essential for radiologists to acquire the skills and knowledge necessary to begin a successful research career in today's funding and academic environment. Many pathways can combine two years of research training and provide fulfillment of existing requirements to achieve specialty certification and subspecialty credentialing. Departments of radiology supporting the beginning qualified investigator should allow him or her approximately 75% research time for the first three years of the academic appointment. Departmental research time accorded faculty members may best be concentrated on a few individuals, providing them sufficient time to be competitive for peer-reviewed grants and enabling research advances to provide a solid foundation for the future of radiologic imaging.

The spectrum of sonographic findings of fibroadenoma of the breast.

There are a number of sonographic findings seen in fibroadenoma of the breast. In a retrospective study, we examined the biopsy results of 59 masses given the sonographic diagnosis of fibroadenoma. We also reviewed the sonograms of an additional 26 biopsy-proven fibroadenomas that were not diagnosed as such with ultrasound. The ultrasound diagnosis was correct in 50 of 76 fibroadenomas (65.8%). Only 12 of the 76 biopsy-proven fibroadenomas had the classic sonographic appearance of a smooth round or oval mass with homogeneous internal echoes. Fourteen fibroadenomas were not visible on the sonograms, even in retrospect. The remaining 50 biopsy-proven fibroadenomas demonstrated one or more "atypical" signs of border irregularity, lobulation, inhomogeneous internal echo texture, or posterior shadowing. There were nine sonographic false positives: five patients had other benign lesions on histology, and four masses believed to be sonographically compatible with fibroadenoma were found to be carcinomas. While breast sonography is frequently a useful modality for breast mass detection, particularly as an adjunct to x-ray mammography, the common overlap in characteristics of benign and malignant masses makes histologic evaluation of all solid masses essential.

Influence of cardiac function on the quality of intravenous digital subtraction arteriograms.

In a retrospective comparison between 22 pairs of matched intravenous digital subtraction angiogram (DSA) images, five angiographers made independent determinations as to which one of each pair was superior in image quality (110 image comparisons). Matched pairs were identical for anatomic region filmed, catheter position during injection, amount of contrast material injected, injection rate, and iodine concentration of the contrast material. Each pair consisted of images from one patient with a normal (less than 1 S.D. above the mean) sodium dehydrocholate circulation time and images from one patient with a prolonged (greater than 1 S.D. above the mean) circulation time. In 85 of the 110 instances (77.3%) an image judged superior in quality to its matched counterpart derived from a DSA exam in a patient with normal circulation time; images from the exam with prolonged circulation time were judged equal in quality to the ones with the normal circulation time in 14 comparisons (12.3%); in 11 comparisons (10%) the images from the DSA with the prolonged circulation time were judged superior to the ones from the DSA with the normal circulation time. These results show that with statistically significant frequency (P less than 0.001) observers judge intravenous DSA images deriving from patients with normal circulation times superior in quality to those deriving from patients with prolonged circulation times.

Detection of acute gastrointestinal bleeding by intra-arterial Tc-99m sulfur colloid scintigraphy in a canine model. Preliminary study.

The diagnostic sensitivities of arteriography, intravenous (IV) Tc-99m sulfur colloid scintigraphy, and intra-arterial (IA) Tc-99m sulfur colloid scintigraphy were evaluated in a canine model of gastrointestinal bleeding. Fifteen dogs were studied at bleeding rates ranging from .4 to 1.0 ml/minute. All three studies were obtained in six of the 15 dogs. Intravenous scintigraphy was superior to angiography in two cases, inferior in three, and equal in one. No significant difference could be shown between these two tests at these bleeding rates. Intra-arterial scintigraphy was superior to angiography in four cases and equal in two (P = .06). It was superior to IV scintigraphy in five cases and inferior in one (P = .10). In this small preliminary study, IA scintigraphy appears to be superior to the other two modalities and may prove useful in the detection of acute bleeding at the time of negative arteriography, and in serial studies in patients receiving Pitressin.

Intracoronary administration of streptokinase in a canine model. Disturbance in thromboxane A2-prostacyclin balance.

The potential impact of local intracoronary infusion of streptokinase (SK) on vascular prostaglandin synthetic pathways was studied in a canine model. Control animals (n = 10) underwent left coronary artery (LCA) infusion of 50,000 units SK for 90 minutes; experimental animals (n = 10) underwent LCA infusion of normal saline. Plasma samples for radioimmunoassay (RIA) of prostacyclin (PGI-2) and thromboxane (TXA-2) were obtained from the coronary sinus (CS) as follows: one sample preinfusion, six samples during infusion, and three samples postinfusion in each animal. Comparisons between control and experimental plasma levels of PGI-2 and TXA-2 were made for each sampling time. The PGI-2 levels remained at or below the lower limits of detectability by RIA (the most sensitive assay available) in both control and experimental animals. TXA-2 levels were higher in experimental than in control animals at all sampling times, with the most significant differences occurring in samples 3 (after 30 minutes of infusion, .001 less than P less than .01), 4 (after 45 minutes of infusion, .05 less than P less than .10), and 5 (after 60 minutes of infusion, .02 less than P less than .05). We suggest (1) it is unlikely that any of the beneficial effects of coronary streptokinase infusions are PGI-2-mediated, (2) that the TXA-2 increases in our model may represent a pathophysiologic-biochemical correlate of previously identified morphologic evidence of endothelial damage in animals infused with fibrinolytic agents, and (3) that our findings may indicate that fibrinolytic infusions produce competing effects: lysis of thrombi and endothelial injury with TXA-2 production.(ABSTRACT TRUNCATED AT 250 WORDS)

The General Electric-Association of University Radiologists Radiology Research Academic Fellowship (GERRAF). An industry-academic collaboration to improve clinical research in radiology.

The association of GE Medical Systems and the AUR represents a unique collaboration between academic radiology and industry that bears important potential for elevating the quality of clinical research in radiology and developing a cadre of high-quality radiologist researchers for the future. The establishment of the GERRAF is especially timely given the new imperatives of the rapidly changing health care environment, with its emphasis on expenditure reduction. The ultimate goals of GERRAF are to develop research leaders for radiology that will provide guidance for appropriate clinical practice, better train future researchers, and secure the role of radiologists in caring for patients.