cssi/SciSciGPT-SciSciNet huggingface dataset:
Iqg1p, a Yeast Homologue of the Mammalian IQGAPs, Mediates Cdc42p Effects on the Actin Cytoskeleton

The Rho-type GTPase Cdc42p has been implicated in diverse cellular functions including cell shape, cell motility, and cytokinesis, all of which involve the reorganization of the actin cytoskeleton. Targets of Cdc42p that interface the actin cytoskeleton are likely candidates for mediating cellular activities. In this report, we identify and characterize a yeast homologue for the mammalian IQGAP, a cytoskeletal target for Cdc42p. The yeast IQGAP homologue, designated Iqg1p, displays a two-hybrid interaction with activated Cdc42p and coimmunoprecipitates with actin filaments. Deletion of IQG1 results in a temperature-sensitive lethality and causes aberrant morphologies including elongated and round multinucleated cells. This together with its localization at the mother–bud neck, suggest that Iqg1p promotes budding and cytokinesis. At restrictive temperatures, the vacuoles of the mutant cells enlarge and vesicles accumulate in the bud. Interestingly, Iqg1p shows two-hybrid interactions with the ankyrin repeat–containing protein, Akr1p (Kao, L.-R., J. Peterson, J. Ruiru, L. Bender, and A. Bender. 1996. Mol. Cell. Biol. 16:168–178), which inhibits pheromone signaling and appears to promote cytokinesis and/or trafficking. We also show two-hybrid interactions between Iqg1p and Afr1p, a septin-binding protein involved in projection formation (Konopka, J.B., C. DeMattei, and C. Davis. 1995. Mol. Cell. Biol. 15:723–730). We propose that Iqg1p acts as a scaffold to recruit and localize a protein complex involved in actin-based cellular functions and thus mediates the regulatory effects of Cdc42p on the actin cytoskeleton.
Phosphorylation of Endothelial Nitric Oxide Synthase in Response to Fluid Shear Stress

Endothelial cells release nitric oxide (NO) more potently in response to increased shear stress than to agonists which elevate intracellular free calcium concentration ([Ca2+]i). To determine mechanistic differences in the regulation of endothelial constitutive NO synthase (ecNOS), we measured NO production by bovine aortic endothelial cells exposed to shear stress in a laminar flow chamber or treated with Ca2+ ionophores in static culture. The kinetics of cumulative NO production varied strikingly: shear stress (25 dyne/cm2) stimulated a biphasic increase over control that was 13-fold at 60 minutes, whereas raising [Ca2+]i caused a monophasic 6-fold increase. We hypothesized that activation of a protein kinase cascade mediates the early phase of flow-dependent NO production. Immunoprecipitation of ecNOS showed a 210% increase in phosphorylation 1 minute after flow initiation, whereas there was no significant increase after Ca2+ ionophore treatment. Although ecNOS was not tyrosine-phosphorylated, the early phase of flow-dependent NO production was blocked by genistein, an inhibitor of tyrosine kinases. To determine the Ca2+ requirement for flow-dependent NO production, we measured [Ca2+]i with a novel flow-step protocol. [Ca2+]i increased with the onset of shear stress, but not after a step increase. However, the step increase in shear stress was associated with a potent biphasic increase in NO production rate and ecNOS phosphorylation. These studies demonstrate that shear stress can increase NO production in the absence of increased [Ca2+]i, and they suggest that phosphorylation of ecNOS may importantly modulate its activity during the imposition of increased shear stress.
Effects of Changes in Structural Hydration of Multiphasic Heterogeneous Calcium Phosphate Powders Created via Auto-Ignition Combustion Synthesis

Calcium phosphate (CaP) materials are commonly used in bone tissue engineering applications since they closely resemble the chemistry of bone and teeth. The inorganic component of mineralized tissue is multiphasic in nature-thus to better replicate those tissues, CaP materials should also be multiphasic. Combustion synthesis is a process that creates multiphasic CaP (HCaP) with low energy input over a relatively short time. The structure and chemistry of HCaP synthesized via auto-ignition combustion synthesis (AICS) varies greatly with respect to structural hydration. Product hydration was accomplished by modifying hydrogen and oxygen content in the combustion reaction by changing the amount of fuel, urea [ ] pre-reaction, and heating or sintering products post-reaction. The reaction equation for this specific system is given below. Calcium nitrate [ ], and ammonium nitrate [ ] are the components that form HCaP. Urea acts as an ignition source and fuel. Changes in the amount of urea dictate the amount of excess hydrogen to form water within the reaction. Excess products formed include water, carbon dioxide, and nitrogen. Salts of the reactants were mixed with 10 milliliters of de-ionized water in a Pyrex beaker, heated on a hot plate for 20 minutes or until the reactants began to foam, and then placed in a muffle furnace at 1000°C until the foam ignited in a combustion reaction. This was noted by the progression of a combustion wave throughout the foam. Post-AICS, products were heated at 105°C for 8 hours and 24 hours and massed to determine water content of the product. Subsequently, the products were sintered at 1000°C for 8 hours and massed again. The primary products formed using AICS are hydroxyapatite (HA), a-tricalcium calcium phosphate (TCP) and hydrated forms of tricalcium phosphate (HTCP). During low temperature heating, 105°C, water content decreases as time increases and the products began to densify. Initial results indicate that surface porosity decreases during the powder densification. XRD shows that peak intensity increases after low temperature heating, indicating an increase in crystallinity and grain orientation. XRD confirms that both crystalline and amorphous phases occur in the hydroxyapatite (HA), a-TCP and HTCP products. The amount of structural hydration has an effect on CaP, and these effects are noted by an increase in density and decrease in porosity as structurally bound water is removed from the system. Future research will be dedicated to determining hydration ratio (amount of urea in the reaction to the amount of water within the products) and a Ca:P ratio that result in optimal powder porosity, ductility and grain size generating a multiphasic HCaP implant biomaterial that accurately replicates natural bony tissue.
Hepatitis B Vaccination in Pregnancy in the United States

Hepatitis B remains a significant health issue worldwide, and contributes significantly to the incidence of cirrhosis and hepatocellular carcinoma. Widespread adoption of hepatitis B vaccination strategies has lead to significant declines in acute hepatitis B infections. Current recommendations for vaccination in the non-pregnant population include vaccinating all persons found to have risk-factors for disease acquisition. Hepatitis B virus is known to occur through vertical transmission or early childhood transmission, and strategies to decrease transmission include avoidance of exposure, avoidance of high-risk behaviors, universal screening of women during pregnancy, and active and passive immunization. It is currently recommended that all pregnant women undergo screening for hepatitis B virus at presentation for prenatal care. Those who engage in high-risk behavior should be re-screened at presentation for delivery. Studies have demonstrated the safety and efficacy of the hepatitis B vaccine in pregnancy, and its use is an important component in prevention of disease acquisition. Pregnant women in the United States who are found to be at risk for disease acquisition should be specifically targeted for vaccination.
Physiology of, an enzyme production by, plant cell cultures

Red kidney bean (Phascolus vulgaris) cells, derived from roof, callus, were grown in suspension culture in shake flasks and in laboratory fermentors using batch and continuous batch culture techniques. The medium contained casein hydrolysate, sucrose, inorganic salts, vitamins, and growth hormones. In continuous batch culture yields of up to 171 g wet weight, (8.5 g dry weight) per liter were obtained in 7 days. Organic nitrogen was used preferentially. Growth on nitrate was considerably slower than on organic nitrogen sources. Indole acetic and naphthalene acetic acids were not essential for good growth of the cells whereas kinetin and 2, 4-D were. The optimum pH for growth was about p11 4.5. The presence of amylase and peroxidase was detected in culture filtrates. Amylase activity was low in either the presence or the absence of starch in the medium. Peroxidase production could be related directly with growth of the culture. Maximum peroxidase yield, as measured by the guaiacol method and expressed as horse radish peroxidase, was 1.25 × 10−8 M.
Psychophysical Investigation of an Auditory Spatial Illusion in Cats: The Precedence Effect

The precedence effect (PE) describes several spatial perceptual phenomena that occur when similar sounds are presented from two different locations and separated by a delay. The mechanisms that pro...
Tracing the Geographic Origins of Major Avocado Cultivars

It has been difficult to infer the genetic history of avocado breeding, owing to the role of hybridization in the origin of contemporary avocado cultivars. To address this difficulty, we used the model-based clustering program, STRUCTURE, and nucleotide polymorphism in 5960 bp of sequence from 4 nuclear loci to examine population structure in 21 wild avocado accessions. The origins of 33 cultivars were inferred relative to the wild sample. Nucleotide sequence diversity in domesticated avocados ranged between 80% and 90% of that observed for the same loci in wild avocado, depending on the diversity statistic used for comparison. Substantial genetic differentiation among 3 geographic groups of wild germplasm corresponded to the classically defined horticultural races of avocado. Previously undetected genetic differentiation was revealed in wild populations from Central Mexico, where 2 subpopulations were distinguished based on elevation and latitude.
Scalable personalized learning

We describe an approach to teaching mid-sized computer science classes in a highly personalized manner. We began with an enumeration of fundamentals that reflect commonly recognized benefits of tutoring: student accountability, customized instruction, clear expectations, emphasis on discussion, and regular evaluation and feedback. For classes of 75 or more some of these appeared unattainable without an army of teaching assistants. But we succeeded, experimenting first in a senior level class of 23 with a design that has remained surprisingly stable as we have transitioned it into discrete math classes of 75 to 80. Our approach includes a novel mix of old and new teaching tactics and techniques combined to create a discussion oriented, high feedback, personalized, group learning environment. We evaluate the costs and benefits associated with our approach, including the surprising result that individual, video-taped exit interviews add little to the instructor's and TA's burden, when all costs and benefits are evaluated.
Planning for Evaluation in Online Learning: University of Hawaii Case Study

With contemporary requirements for objective measurement, program evaluation is a certain necessity. Most program evaluation is designed in response to external demands for assessment. Moreover, such evaluation is typically developed only after programs already exist. However, the proliferation of online learning provides new opportunities for approaching evaluation. Specifically, many higher education institutions are currently augmenting existing campus-based programs with online learning—either by hybridizing traditional delivery or by providing parallel online options. At the University of Hawaii, while designing a parallel online delivery model for an existing campus-based program, careful consideration was given to the unique requirements for evaluation and assessment. In this way, an overall plan for evaluation was developed that incorporated multiple layers of assessment: from specific programmatic to internal university to external accreditation requirements. Commonalities among the multiple layers were considered to develop a single, overall evaluation approach. In a case study model, this paper describes eight practical steps taken to develop an overall, effective evaluation model.
The statistics of radar backscatter phase and a comparison of Doppler frequency estimates

The statistics of the phase of radar backscatter from the ocean surface is examined using scatterometer data from the SAXON FPN experiment. >
3-(2-Amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-5-fluoro-3-hydr-oxy-1-methyl-indolin-2-one methanol hemisolvate

In the title compound, C13H13FN4O3·0.5CH3OH, mol­ecules are packed in the crystal structure by a series of O—H⋯N, N—H⋯O, N—H⋯F and O—H⋯O inter­molecular hydrogen bonds. The indole and creatinine units make a dihedral angle of 60.80 (4)°.
A Nazi-Looted Art Tribunal

This article is a ten-page article to appear in a 1:5 World Arbitration and Mediation Review (2007), a peer-reviewed Juris Publishing journal produced at the Penn State Dickenson School of Law. It is a shorter rendition of my thesis at 73 Brooklyn Law Review 155 (Dec. 2007) entitled Reconciling Individual and Group Justice with the Need for Repose in Nazi-Looted Art Disputes: Creation of an International Tribunal. Abstract: The recent push for Holocaust reparations, which resulted in European, domestic and international funds, left a significant gap pertaining to Nazi-looted art. Claims to Nazi-looted art are exploding, creating a tremendous problem for the art market. This Article concludes that the best remedy for the problem is the creation of an international tribunal with compulsory jurisdiction to resolve claims to Nazi-looted art in a manner akin to an equitable hybrid of mediation and binding arbitration. The Tribunal would provide justice to both individual claimants with strong claims and other claimants who probably could not win in court but are nonetheless deserving of relief. It also would provide the repose so desperately needed by the art community. With the upcoming administration change in the White House, this idea has a realistic chance of being implemented and should be explored.
A Participatory Learning and Action (PLA) Approach to Enhancing Linkage to HIV Care Among Youth

Purpose: Early linkage to HIV care is critical for viral suppression and to prevent HIV transmission. However, people with HIV, and especially adolescents, delay linkage to care. Studies estimate between 66% and 75% of newly diagnosed HIV-positive individuals are linked to care. The purpose of this study was to utilize a Participatory Learning Action (PLA) approach to engage community members in identifying barriers to HIV linkage to care and creating an action plan. Methods: Over 50 individuals from various community organizations participated in a series of meetings to address HIV linkage to care barriers. Identified barriers were related to the health care system, lack of community collaborations, social factors such as stigma, and characteristics of risk populations. Results: dOne of the solutions identified to address individual barriers was the creation of an application (app) for smart phones that includes resources and how to access care. This app is a way to reach youth on a platform that they are familiar with using. The app was created and allows to search for various resources related to HIV/STD testing and care, directions to nearby services, and the ability to call linkage workers at various sites. Conclusions: HIV linkage to care is a major public health concern. Engaging community stakeholders through a PLA approach can be effective in improving engagement in care of people with HIV. The PLA approach has been shown to be an effective approach to mobilize the community and engage stakeholders in addressing a shared concern and make a collective impact. Sources of Support: Gilead Sciences Inc.
Temporal Associations Between Sleep and Physical Activity Among Overweight/Obese Youth

Objective Examine average interindividual and temporal intraindividual associations between time of sleep onset (sleep onset), total sleep time (TST), and minutes in moderate-to-very-vigorous physical activity per hour (MVPA/h) among overweight/obese youth. Methods Overweight/obese youth (n = 134; 7-12 years) wore an accelerometer for 16+ hr/day, 5-7 days, which provided daily objective estimates of MVPA/h, TST, and sleep onset. Results Multilevel models revealed an intraindividual effect of TST, such that nights with longer TST preceded less MVPA/h during the midnight-to-midnight monitoring period; a significant random effect qualified this relationship. Average interindividual TST did not predict mean MVPA/h, whereas sleep onset significantly predicted mean MVPA/h. Conclusions Later time of sleep onset (as opposed to TST) was the strongest predictor of group-level decreased physical activity. At the individual level, longer TST than usual predicted less MVPA/h than usual. Results suggest the need for more person-centered research and a greater focus on sleep timing among youth.
Insecticides Tested Versus Grasshoppers: Correlations Between Results of Ground and Aerial Applications

The comparative effectiveness of 33 insecticides was tested vs. grashoppers on rangeland, from 1960 through 1972. The insecticides were applied with ground equipment and from the air. Mortalities produced by ground application and estimated effective doses were relatively poor indicators of the results that were obtained by aerial application, but the correlations were surprisingly good in view of the diverse conditions of testing.
Control of Macrosiphum barri Essig and Its Damage to Lettuce Seed Plants

Repeated field applications of selected insecticides to seed lettuce satisfactorily controlled infestations of the lettuce seed stem aphid, Macrosiphum barri Essig. These treatments also gave a very significant reduction of an infestation by the two-spotted spider mite ( Tetranychus telarius (L.)), but they did not give an adequate reduction of lettuce mosaic. A tree fold increase in yield of lettuce seed was obtained by the use of repeated applications of parathion sprays and dusts for control of the lettuce seed stem aphid. This increased yield was significantly higher than that obtained from plots treated with other materials, and was judged to be economically satisfactory. There was also a very significant increase in the weight and size of the lettuce seeds. This was also confirmed by cage tests. This aphid caused a reduction of about 66% in yield of lettuce seed obtained from untreated plots. It was possible to demonstrate that these stem aphids caused a lettuce seed loss of as much as 59%, when artificially infested plants were grown in field cages. However, the exact degree of infestation necessary to produce economic loss of seed was not established. The feeding of this aphid also produced a significant redaction in the number of normal seedlings. In addition, there was a decrease in the mean emergence period of the aphid-damaged seeds, indicating a more rapid germination. A significant increase in damage to cotyledons of the seedlings was obtained from thc aphid-damaged seeds, which showed that this aphid is one cause of "red cotyledon" of lettuce seedlings.
Toxicity of Selected Insecticides Applied Topically to Lygus hesperus

Lygus hesperus Knight collected from alfalfa at 2 California locations were treated topically with a total of 19 insecticides during the period 1968–75. LD50 values were developed. For some insecticides, comparisons of toxicity are made between 2 or more years and between locations. The development of resistance by L. hesperus to malathion and trichlorfon is evident at both locations, and resistance to monocrotophos is evident at one location. There is a trend toward greater resistance to organophosphorous and carbamate insecticides at the location with a greater history of use of insecticides.
Photographs and Descriptions of Cup-Fungi—V. Discina Venosa

(1917). Photographs and Descriptions of Cup-Fungi—V. Discina Venosa. Mycologia: Vol. 9, No. 2, pp. 53-54.
Where are the dedicated scholars of management learning and education

The vibrancy of a field is predicated on the attraction and sustained efforts of increasing numbers of dedicated scholars. However, in management education research, historically this level of dedi...
Incompatibility in Food Production Process——Taking Henan Province as an Example

In the analysis food production process's incompatibility,to promote the food production in the main producing areas for the national food security is important.Using the food production statistical data,the food production's succession tendency and the spatial variation are analyzed.Grain yield's large scale growth mainly relies on the grain per unit area yield enhancement.The land delivers(grain per unit area yield) high and the low efficiency of resources coexist.Food production cost increase and food price rise cannot synchronous,appeared commissariat advocate produce a division of fiscal income and net income of farmers" double low" phenomenon,become an obstacle to food security.Fluctuations in food production and food policy are closely related.To ensure national food security,Food policy can play an important role.The grain main production region in ensuring national food security has important role.Through the policy implementation of the fiscal,monetary and price to promote the development of major grain producing areas,explores a sustained,stable and harmonious development way that complies with the principle of synchronization to improve food production and farmers ' income,benefit coordinated between the main production areas and sales areas,not to sacrifice the interests for ecology and the environment in the grain main production area.
Erythropoietin production in a primary culture of human renal carcinoma cells maintained in nude mice

The present studies report erythropoietin (Ep) production in primary cultures of a human renal carcinoma from a patient with erythrocytosis that has been serially transplanted to BALB/c nude mice. The levels of erythropoietin in the culture media were estimated using the exhypoxic polycythemic mouse assay (EHPCMA), fetal mouse liver erythroid colony- forming technique (FMLC), and a radioimmunoassay (RIA). The spent culture media of the exponentially growing cells contained less than 10 mU/ml of Ep measured by RIA. However, after the cells became confluent, Ep levels (RIA) in the spent media showed a marked increase to approximately 300 mU/ml. Ep levels estimated using the FMLC and EHPCMA were approximately 2/3 and 1/10, respectively, of those measured by RIA. Rabbit antiserum to highly purified human urinary Ep (70,400 U/mg protein) was utilized for immunocytochemical (peroxidase-antiperoxidase method) localization of Ep in the cultured cells. Very few of the cells in exponential growth exhibited Ep-like immunoreactivity, whereas intense Ep-like immunoreactivity was observed in the cytoplasm of the cells maintained in culture for a prolonged period after reaching confluency. The most intense staining was observed in some of the cells forming domes. The domes developed after the cells reached confluency, and their numbers increased with increasing time in confluent culture, in parallel with the increase in Ep levels in the spent media. This primary cell culture system of a renal cell carcinoma maintained in nude mice, which produces immunologically and biologically active Ep, may provide a useful model for studies of the mechanism of Ep production.
Production of W±H from heavy-quark fusion

The supersymmetric two-Higgs-doublet model is adopted to study the production of a charged Higgs boson ({ital H}{sup {minus plus}}) in association with a {ital W} boson ({ital W}{sup {plus minus}}) at future hadron colliders. The subprocess reactions {ital t{bar t}}{r arrow}{ital W}{sup {plus minus}}H{sup {minus plus}}, {ital gt}{r arrow}{ital W}{sup {plus minus}}H{sup {minus plus}}t, {ital g{bar t}}{r arrow}{ital W}{sup {plus minus}}H{sup {minus plus}}{bar t}, and {ital gg}{r arrow}{ital W}{sup {plus minus}}H{sup {minus plus}}t{bar t} are combined to find the total rate.
Annotating Logical Forms for EHR Questions

This paper discusses the creation of a semantically annotated corpus of questions about patient data in electronic health records (EHRs). The goal is to provide the training data necessary for semantic parsers to automatically convert EHR questions into a structured query. A layered annotation strategy is used which mirrors a typical natural language processing (NLP) pipeline. First, questions are syntactically analyzed to identify multi-part questions. Second, medical concepts are recognized and normalized to a clinical ontology. Finally, logical forms are created using a lambda calculus representation. We use a corpus of 446 questions asking for patient-specific information. From these, 468 specific questions are found containing 259 unique medical concepts and requiring 53 unique predicates to represent the logical forms. We further present detailed characteristics of the corpus, including inter-annotator agreement results, and describe the challenges automatic NLP systems will face on this task.
The direct wave root in marine seismology

Abstract The “direct wave root” is an evanescent wave which is observed below the sea floor when the direct water wave is incident on the sea floor from above at supercritical angles. For shallow borehole receivers, it is the largest amplitude arrival on large offset seismograms. The wave has been studied and observed in electromagnetics and acoustics but this paper is the first report of the “direct wave root” in marine seismology. Theoretically, an expression for the “direct wave root” can be obtained from a branch line integral in the complex ray parameter plane for the transmission problem between two acoustic half-spaces. Synthetic seismogram analysis based on the discrete wavenumber (or reflectivity) method can be applied to study the more realistic cases of elastic bottoms, gradients beneath the sea floor, and intrinsic attenuation. Steep gradients below the sea floor give amplitude-depth relations which are not exponential. Attenuation (Q = 40) affects amplitudes less than 1 dB. Observations of the “direct wave root” have been made at the Deep Sea Drilling Project Site 504B in the Costa Rica Rift area and the observed properties are consistent with theory. It is proposed that more detailed measurements of the decay of the “direct wave root” amplitude with depth be used to obtain high resolution measurements of upper crustal elastic properties at seismic frequencies.
Trauma-Focused Cognitive Behavioral Therapy

Exposure to traumatic events during childhood is relatively common and is related to a host of adverse short- and long-term outcomes. Trauma-Focused Cognitive Behavioral Therapy (TF-CBT; Cohen et al. Treating trauma and traumatic grief in children and adolescents. The Guildford Press, New York, 2006) is the leading intervention for childhood trauma, having amassed the most empirical support (Cohen et al. J Am Acad Child Adolesc Psychiatry 4: 414–430, 2010). TF-CBT is a conjoint child and parent therapy model that consists of nine trauma-focused components that spell the acronym PRACTICE. In this chapter, we provide a brief overview of the TF-CBT model and PRACTICE components. Next, we describe the theoretical underpinnings of TF-CBT, highlighting such concepts as stress management, gradual exposure, cognitive theory, and observational learning via caregiver involvement. We then illustrate how to implement TF-CBT using a case example. Special challenges frequently observed in TF-CBT, and how to overcome these difficulties, are then discussed. We conclude by describing the significant empirical support for TF-CBT and outlining areas for future TF-CBT research.
Combining Semi-Classical and Quantum Mechanical Methodologies for Nuclear Cross-Section Calculations Between 1 MeV and 5 GeV

With a goal to develop a nuclear cross-section code usable over the wide energy range of 1 MeV to 5 GeV, one option is to combine intranuclear cascade, pre-equilibrium, and Hauser-Feshbach models in existing codes. However, the first two models are semi-classical while the third one is quantum mechanical, and combining them is not straightforward because the third model requires spin and parity distributions for all excited states that cannot be supplied by either one of the first two models. Approximations to overcome this difficulty are described in this paper. Success of this combined model will allow nuclear data evaluations for a large number of materials whose cross sections are needed in a wide range of applications, including the design, operation, and future upgrades of the SNS (1 GeV proton). The incident particles may be neutrons, protons, charged pions, or photons. Though only partially completed at this time, the new model compares well with experimental radionuclide production cross sections from thresholds to 2.6 GeV for proton-induced reactions on Fe.
Vibration of Nearly Periodic Structures and Mistuned Bladed Rotors

This is the first comprehensive volume on nearly periodic structures and mistuned blade vibration. Alok Sinha presents fundamental concepts and state-of-the-art techniques in the analysis of free and forced response of a nearly periodic structure, weaving together his own work (covering thirty-five years of research in this field) with works by other researchers. He also discusses similarities between tools used in bladed rotor analysis and condensed matter physics. Specific subjects covered include the reasons behind mode localization, the reasons behind amplitude amplification of steady-state response, state-of-the-art computational techniques for mistuned bladed rotors including multistage rotors, identification of mistuning from measured response, vibration localization in linear atomic chains, and analysis of two-dimensional periodic structures.
Fine structure of conformational ensembles in adenylate kinase.

Adenylate kinase (ADK) catalyzes the reversible Mg2+ -dependent phosphoryl transfer reaction Mg2+ +2ADP ↔Mg2+ +ATP + AMP in essential cellular systems. This reaction is a major player in cellular energy homeostasis and the isoform network of ADK plays an important role in AMP metabolic signaling circuits. ADK has 3 domains, the LID, NMP, and CORE domains, that undergo large conformational rearrangements during ADK's catalytic cycle. In spite of extensive experimental and computational studies, details of the conformational pathway from open to closed forms remain uncertain. In this paper we explore this pathway using coarse-grained molecular dynamics (MD) trajectories of ADK calculated by GROMACS using a SMOG model and classify the conformations within the resultant trajectories by K-means clustering. ADK conformations segregate naturally into open; intermediate; and closed forms with long-term residence in the intermediate state. Structural clustering divides the intermediate conformation into 3 sub-states that are distinguished from one another on the basis of differences in both structure and dynamics. These distinctions are defined on the basis of a number of different metrics including radius of gyration, dihedral angle fluctuation, and fluctuations of interatomic pair distances. Furthermore, differences in the sub-states appear to correspond to the distinct ways each sub-state contributes to the molecular mechanism of catalysis: One sub-state acts as a gate-way to the open conformation; one sub-state a gate-way to the closed conformation. A third intermediate sub-state appears to represent a metastable off-pathway structure that is nevertheless frequently visited during the passage from open to closed state.
UV- and Thermo-Controllable Azobenzene-Decorated Polycarbodiimide Molecular Springs

Molecular switches offer wide applicability through conformational changes which can be triggered by external stimuli. Azobenzenes are excellent candidates to contribute toward a rational design of molecular switches because they exist as either cis or trans isomers as a result of the dynamic photoisomerization process. In this study, we leverage the azobenzene stimuli response by attaching it as a pendant group on polycarbodiimides synthesized using screw sense polymerization. The exposure of the polymer sample in solution to UV light induces the transformation of the azobenzene pendant groups to the cis isomer with re-emergence of the trans conformer under visible light or heat. Corroborating experimental and computational data reveal that these events induce spring-like expansion–contraction motions throughout the helical backbone. Our finding suggests the use of polycarbodiimide-derived photoswitches as dynamic materials in biological applications and materials science.
EphA2 stimulates VCAM-1 expression through calcium-dependent NFAT1 activity

Endothelial cell activation by proinflammatory stimuli drives leukocyte recruitment through enhanced expression of counter-receptors such as vascular cell adhesion molecule-1 (VCAM-1). We previously demonstrated that activation of the receptor tyrosine kinase EphA2 with its ligand ephrin-A1 induces VCAM-1 expression. Here, we sought to characterize the proinflammatory signaling pathways involved. Analysis of over-represented transcription factors in ephrin-A1-induced genes identified multiple potential transcriptional regulators, including the Rel family members nuclear factor-κB (NF-κB/p65) and nuclear factor of activated T-cells (NFAT). While ephrin-A1 failed to induce endothelial NF-κB activation, NF-κB inhibitors prevented ephrin-A1-induced VCAM-1 expression, suggesting basal NF-κB activity is required. In contrast, ephrin-A1 induced a robust EphA2-dependent increase in NFAT activation, and mutation of the NF-κB/NFAT-binding sites in the VCAM-1 promoter blunted ephrin-A1-induced promoter activity. NFAT activation classically occurs through calcium-dependent calcineurin activation, and inhibiting NFAT signaling with calcineurin inhibitors (cyclosporine A, FK506) or direct NFAT inhibitors (A-285222) was sufficient to block ephrin-A1-induced VCAM-1 expression. Consistent with robust NFAT activation, ephrin-A1-induced an EphA2-dependent calcium influx in endothelial cells that was required for ephrin-A1-induced NFAT activation and VCAM-1 expression. This work provides the first data showing EphA2-dependent calcium influx and NFAT activation and identifies NFAT as a novel EphA2-dependent proinflammatory pathway in endothelial activation.
Infants Are More Likely Than Older Children to Have Surgery for Cervical Infections.

Objectives. To identify differences in cervical infection management in infants versus older children. Methods. Charts of patients 0–18 years, diagnosed with a cervical infection at our institution between 2004 and 2015, were included. Age, gender, presenting symptoms, comorbidities, CT scan findings and management including admission, procedures, antibiotics, cultures, length of stay, readmission rates, and complications were included. Results. 239 patients were included: mean age was 4.6 years, with 55.6% boys and 44.4% girls. Mean length of stay was 3.2 days, with no significant difference between age categories. 12.55% were readmitted within 30 days with no significant difference when stratified for age (p = 0.268). The most common presenting symptoms were fever (74.3%), swelling (71.4%), and neck pain (48.2%). Infants had fewer symptoms documented than older children. 51% has lateral neck infections, and these were more common in younger children (p < 0.001). The most common antibiotic used was amoxicillin-clavulanic acid in 53.96% of inpatients and 48.05% of outpatients. Infants were most likely to have MRSA isolates (29.2% versus 11.7% of older children, p = 0.011). 70.0% went to the operating room for incision and drainage procedures. Younger children were more likely to undergo surgery, with an odds ratio of 2.38 for children under 1 year. (p = 0.029). 90.9% of infants underwent surgery with radiolucencies of at least 1 cm diameter in contrast to 50% of children over 8 years old. Conclusions. This study emphasizes the importance of considering early operative treatment of cervical abscesses in infants despite fewer symptoms and smaller radiolucencies on CT.
Schwarz’ Lemma and its Many Applications

This chapter is fairly tightly unified around the following simple result: Theorem 6.1 (Schwarz’ Lemma) Let f be holomorphic and bounded by 1 in D = D(0, 1) and f(0) = 0. Then (i) ∣f′(0)∣ ≤ 1 (ii) ∣f(z)∣ ≤ ∣z∣ ∀z ∈ D and equality in (i) or in (ii) for some non-zero z occurs if and only if (iii) f(z) = cz for some unimodular complex constant c.
Management and Disposition of Atrial Fibrillation in the Emergency Department: A Systematic Review.

Introduction Management of atrial fibrillation (AF) and atrial flutter (AFL) in the emergency department (ED) varies greatly, and there are currently no United States guidelines to guide management with regard to patient disposition after ED treatment. The aim of this systematic review was to evaluate the literature for decision aids to guide disposition of patients with AF/AFLin the ED, and assess potential outcomes associated with different management strategies in the ED. Methods and results A systematic review was done using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE, combining the search terms "Atrial Fibrillation", "Atrial Flutter", "Emergency Medicine", "Emergency Service", and "Emergency Treatment". After removal of duplicates, 754 articles were identified. After initial screening of titles and abstracts, 69full text articles were carefully reviewed and 34 articles were ultimately included in the study based on inclusion and exclusion criteria. The articles were grouped into four main categories: decision aids and outcome predictors, electrical cardioversion-based protocols, antiarrhythmic-based protocols, and general management protocols. Conclusion This systematic review is the first study to our knowledge to evaluate the optimal management of symptomatic AF/AFLin the ED with a direct impact on ED disposition. There are several viable management strategies that can result in safe discharge from the ED in the right patient population, and decision aids can be utilized to guide selection of appropriate patients for discharge.
Inflammatory eruptions associated with immune checkpoint inhibitor therapy: A single-institution retrospective analysis with stratification of reactions by toxicity and implications for management.

Background There is increasing recognition of distinct inflammatory eruptions associated with checkpoint inhibitors. A better understanding of their severity, therapeutic response, and impact on cancer treatment is needed. Objective To analyze the different rashes associated with immunotherapy referred to our institution's oncodermatology clinic and inpatient consultative service and to evaluate their therapeutic response and impact on immunotherapy. Methods We retrospectively reviewed the medical records of patients referred to the oncodermatology clinic or inpatient dermatology service during 2016-2018 at Yale-New Haven Hospital for eruptions that developed during immunotherapy. Results In total, 98 patients (51 men, 47 women) treated with checkpoint inhibitors developed 103 inflammatory eruptions, with a range of mean latency of 0.2-17.7 months. A minority of patients (25/103; 24.3%) required immunotherapy interruption; most of these cases involved immunobullous (7/8; 87.5%), lichenoid (8/26; 30.8%), maculopapular (6/18; 33.3%), and Stevens-Johnson syndrome–like (2/2, 100%) reactions. Only 3 of 16 (18.8%) patients who had their immunotherapy interrupted had a grade 2 or 3 flare on rechallenge. Most reactions (93/103; 90.3%) responded to dermatologic therapy or immunotherapy interruption. Limitations This was a retrospective study from a single tertiary care center. Conclusion A variety of inflammatory reactions might occur from immunotherapy with differing degrees of severity. While most rashes responded to topical treatment, immunobullous and exfoliative presentations frequently interrupted immunotherapy. Increased awareness and early recognition could reduce the need for unnecessary immunotherapy interruption.
Uncovering the role admixture in health disparities: Assocication of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans

ABSTRACT In African Americans (AA), the proportion of West African ancestry (WAA) may explain the genetic drivers of health disparities in disease. Analysis of RNA sequencing data from sixty AA-derived primary hepatocytes identified 32 gene expression profiles associated with WAA (FDR
Challenges in the Use of Performance Data in Management: Results of a National Survey of Human Service Nonprofit Organizations

Nonprofit organizations are increasingly pressured to measure their performance. Although several studies identify driving factors of measuring performance in public organizations, there is limited...
Outcome of a High-Frequency Transcutaneous Electrical Nerve Stimulator (hfTENS) Device for Low Back Pain: A Randomized Controlled Trial.

OBJECTIVE This controlled trial examined the benefit of a high-frequency transcutaneous electrical nerve stimulation (hfTENS) device (the Quell, NeuroMetrix, Inc., Waltham, MA, U.S.A.) for patients with chronic low back pain (CLBP). METHODS Thirty-five (n = 35) participants were randomly assigned to use the device each day for 3 months (experimental group) and were compared with 33 subjects without the device (treatment-as-usual control group). All patients were instructed to complete baseline questionnaires and were assessed on thresholds of pressure pain and mechanical temporal summation as part of standardized quantitative sensory testing (QST). The subjects also uploaded smartphone applications (apps) for tracking use of the hfTENS and for daily pain assessment. Each participant completed weekly phone interviews, was prompted to complete daily pain app assessments, and was asked to repeat the baseline questionnaires again after 6 weeks and 3 months. RESULTS Sixty percent of the subjects were female, 77.9% were Caucasian, and the average age was 46.2 years. Significant reductions in pain intensity (P < 0.01) and activity interference (P < 0.025) and significant improvements in pain catastrophizing (P < 0.025) were noted in the experimental group compared with the control group. No group differences were found on depression, anxiety, or pain-related disability. Older subjects with a longer duration of pain tended to use the hfTENS more often. Subjects who showed greater sensitivity based on QST results revealed increased use of the hfTENS (P < 0.025) and tended to believe that the hfTENS was more helpful in reducing their back pain, but these findings did not reach significance (P = 0.09). CONCLUSION These results suggest that hfTENS can have a moderate effect in reducing pain and improving quality of life in low back pain patients. Further trials designed to determine the mechanism of action of the hfTENS are needed.
Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells

Long-chain bases are present in the oral cavity. Previously we determined that sphingosine, dihydrosphingosine, and phytosphingosine have potent antimicrobial activity against oral pathogens. Here, we determined the cytotoxicities of long-chain bases for oral cells, an important step in considering their potential as antimicrobial agents for oral infections. This information would clearly help in establishing prophylactic or therapeutic doses. To assess this, human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), and dendritic cells (DC) were exposed to 10.0-640.0 μM long-chain bases and glycerol monolaurate (GML). The effects of long-chain bases on cell metabolism (conversion of resazurin to resorufin), membrane permeability (uptake of propidium iodide or SYTOX-Green), release of cellular contents (LDH), and cell morphology (confocal microscopy) were all determined. GE keratinocytes were more resistant to long-chain bases as compared to GF and DC, which were more susceptible. For DC, 0.2-10.0 μM long-chain bases and GML were not cytotoxic; 40.0-80.0 μM long-chain bases, but not GML, were cytotoxic; and 80.0 μM long-chain bases induced cellular damage and death in less than 20 min. The LD50 of long-chain bases for GE keratinocytes, GF, and DC were considerably higher than their minimal inhibitory concentrations for oral pathogens, a finding important to pursuing their future potential in treating periodontal and oral infections.
Exacting collaboration: performance as pedagogy in interdisciplinary contexts

In this field report from a STEAM (science, technology, engineering, arts, and mathematics) study abroad programme, the author describes how students came to see collaboration – a key component of ...
Dexamethasone Intravitreal Implant Injection in Eyes with Comorbid Hypotony

Purpose To evaluate outcomes in patients with hypotony treated with intravitreal dexamethasone implant (Ozurdex). Design Retrospective cohort study. Participants Thirteen patients (15 eyes) that received a total of 99 dexamethasone implant injections on occasions at which the intraocular pressure was low, meeting the definition of statistical hypotony. Methods The medical records of 13 patients (15 consecutive eyes) receiving 1 or more intravitreal dexamethasone implants between December 2014 and April 2017 were reviewed retrospectively. Hypotony was defined as intraocular pressure less than 6.5 mmHg. The indications for intravitreal dexamethasone implant injection were intermediate or posterior uveitis (86.7%), diabetic macular edema (13.3%), and/or cystoid macular edema (6.7%). Main Outcome Measures The primary outcome measures were safety outcomes and best visual acuity within 6 months of the final intravitreal dexamethasone implant injection in a hypotonous eye. Results In 15 eyes (13 patients), 99 injections were administered to eyes under circumstances of hypotony. Uveitic cystoid macular edema or diabetic macular edema was reduced after treatment in all cases. No complications were noted during the injection procedure. Three complications were noted in 2 patients after injection. Pseudophakodonesis and mild vitreous hemorrhage immediately after injection were noted in 1 patient, and a case of delayed-onset vitreous hemorrhage with pigment release was noted in another. All 3 complications resolved without intervention. The primary end point of this study—mean visual acuity—was stable over the follow-up period. In patients with hypotony whose intraocular pressure normalized during the follow-up period, this was attributable to management of glaucoma surgery–related complications rather than an effect of the intravitreal dexamethasone implant. Conclusions Intravitreal dexamethasone implant injection is a reasonable treatment option for patients with comorbid hypotony in whom clinical findings warrant treatment with a sustained-delivery intravitreal steroid implant. Further studies, including imaging of zonules before and after intravitreal dexamethasone implant injection in a hypotonous eye, could help define risks to intraocular lens stability with this procedure.