cssi/SciSciGPT-SciSciNet huggingface dataset:
Use of the Kidney Failure Risk Equation to Determine the Risk of Progression to End-stage Renal Disease in Children With Chronic Kidney Disease.

Importance The kidney failure risk equation (KFRE) has been shown to accurately estimate progression to kidney failure in adults with chronic kidney disease (CKD). Use of the KFRE in children with CKD, if accurate, would help to optimize planning for end-stage renal disease (ESRD) care. Objective To determine whether the KFRE adequately discriminates the risk of ESRD in children with CKD. Design, Setting, and Participants This retrospective cohort study included 603 children with an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2in the Chronic Kidney Disease in Children study, a national multicenter observational study. Data were collected from January 1, 2005, through July 31, 2013, and analyzed from September 30, 2016, through September 8, 2017. Exposures The primary predictive factors were the 4-variable (age, sex, bedside Schwartz estimated glomerular filtration rate, and ratio of albumin to creatinine levels) and 8-variable (4 variables plus serum calcium, phosphate, bicarbonate, and albumin levels) KFREs, which provide 1-, 2-, and 5-year estimates of the risk of progression to ESRD. Main Outcomes and Measures Time to ESRD. The Cox proportional hazards model was used to examine the association between the KFRE score and time to ESRD. C statistics were used to discriminate ESRD risk by the KFRE, with a value of greater than 0.80 indicating strong discrimination. Results Of the 603 children included in the study, 378 were boys (62.7%) and 225 were girls (37.3%); median age at study entry was 12 years (interquartile range, 8-15 years). Median estimated glomerular filtration rate was 44 mL/min/1.73 m2. Four hundred fifty-seven participants (75.8%) had a nonglomerular cause of CKD. Median observation time was 3.8 years (interquartile range, 1.7-6.2 years); 144 (23.9%) developed ESRD within 5 years of enrollment. The 4-variable KFRE scores discriminated risk of ESRD, with C statistics of 0.90, 0.86, and 0.81 for the 1-, 2-, and 5-year risk scores, respectively. Results were similar using the 8-variable equation. Conclusions and Relevance The KFRE is a simple tool that provides excellent discrimination of the risk of ESRD. Results suggest that the KFRE could be incorporated into the clinical care of children with CKD to aid in anticipatory guidance, timing of referral for transplant evaluation, and planning for dialysis access.
Uric acid and the vaccine adjuvant activity of aluminium (oxy)hydroxide nanoparticles

In an effort to improve the adjuvanticity of insoluble aluminium salts, we discovered that the adjuvant activity of aluminium salt nanoparticles is significantly stronger than aluminium salt microparticles, likely related to nanoparticle's stronger ability to directly activate NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome as the nanoparticles are more efficiently taken up by phagocytic cells. Endogenous signals such as uric acid from cell damage or death caused by the cytotoxicity of aluminium salts are thought to indirectly activate inflammasome, prompting us to hypothesise that the potent adjuvant activity of aluminium salt nanoparticles is also related to their ability to stimulate uric acid production. In the present study, we prepared aluminium (oxy)hydroxide nanoparticles (∼ 30-100 nm) and microparticles (X50, 9.43 μm) and showed that intraperitoneal injection of mice with the nanoparticles, absorbed with ovalbumin, led to a significant increase in uric acid level in the peritoneal lavage, whereas the microparticles did not. The aluminium (oxy)hydroxide nanoparticles' ability to stimulate uric acid production was also confirmed in cell culture. We concluded that the stronger adjuvant activity of insoluble aluminium (oxy)hydroxide nanoparticles, relative to microparticles, may be attributed at least in part to their stronger ability to induce endogenous danger signals such as uric acid.
Improve the mechanical properties and wear resistance of Cr-C thin films by adding Al2O3 particles

Abstract In this study, alumina particles with various contents of 5, 10, 15, and 20 g/L in bath are co-deposited within Cr-C matrix by electrodeposition from a trivalent chromium bath. The electrodeposition is performed at a current density of 10, 15, 20 and 25 A/dm2, respectively, for 30 min. The influences of plating parameters including alumina concentration in the plating bath and current density on the volumetric percent of co-deposited particles in coating, deposition rate, morphology, hardness, corrosion resistance and wear behavior of electrodeposited Cr-C/Al2O3 composite coatings are evaluated and compared with that of electrodeposited Cr-C coatings. Our result shows that the codeposited particles percent, a determinant factor governing the hardness, corrosion resistance, and wear resistance of the coating, is influenced by concentration of alumina in bath and the current density. The maximum content of Al2O3 particles of 21.1 vol% is achieved at an Al2O3 concentration of 15 g/L in bath and a current density of 20 A/dm2. An increase of Al2O3 particles content in deposits increases the hardness of the coatings and significantly increases the corrosion as well as the wear resistance of the coatings, whereas the average friction coefficient decreases. The highest hardness approximately at 1075 HV is obtained from the Cr-C/Al2O3 composite coating with Al2O3 content of 21.5 vol%.
Implementation of the Department of Veterans Affairs' first point-of-care clinical trial.

The Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) and the Stanford Center for Innovative Study Design have developed a new method for the implementation of experimental clinical research. The point-of-care clinical trial (POCCT) is designed to be embedded directly into the clinical care setting thereby addressing the issues of cost and translation, and creating an integrated environment of research-based care. The POCCT capitalizes on the Veterans Affairs (VA) electronic medical record (EMR) system to perform study activities traditionally conducted by a study team such as enrolment, randomization, and longitudinal data collection. In addition, as evidence accumulates in favor of a specific intervention, it can be transitioned to decision support in the same EMR. As a result, POCCT integrate clinical research and clinical care providing a valuable tool for achieving the vision of a ‘learning healthcare system’. In this article, the implementation of the VA's first POCCT is described, citing experience to date with an ongoing comparative effectiveness study comparing two common regimens of administering insulin. The informatics-related challenges and strategies used to overcome them are the primary focus of this article, with additional consideration of the potential of POCCT to diffuse within and beyond the VA healthcare system.
Why Is It So Hard to Build and Validate Discrete Event Simulation Models of Manufacturing Facilities

Discrete event simulation modeling methods are widely used to evaluate the performance of manufacturing systems. These models provide factory management the ability to test different manufacturing methods and operational policies before a factory is built, or before significant changes are made to a facility. These policies could include testing of proposed manufacturing methods, layout methodologies, production equipment assignment strategies, equipment maintenance and repair policies, operator staffing scenarios, and factory automation configurations. Using these models, it is possible to evaluate the performance or predict future performance based on a detailed sensitivity analysis of these different operating variables. This ability has proven to be invaluable, especially if the analysis is performed before major investment decisions are made or prior to finalizing factory designs. Consequently, discrete event simulation modeling continues to be an enabling capability for performance evaluation of manufacturing systems.
The course of cryptococcal capsular polysaccharide antigenemia/human cryptococcal polysaccharide elimination kinetics

The detection of cryptococcal polysaccharides in the serum is diagnostic of cryptococcosis in the absence of rheumatoid factor. The significance of the continued detection of this antigen in the serum during antifungal therapy is not known. Prolonged anti-genemia might indicate ongoing active infection, delayed clearance of the polysaccharides from the blood, or continued release of the polysaccharide antigens from a reservoir of nonviable organisms. In seven cases of cryptococcosis with prolonged and high levels of cryptococcal polysaccharide antigenemia, the courses of antigenemia were determined. During the convalescent phase, the T1/2's were approximately 48 hours for the antigen clearance in all the cases studied. The polysaccharide antigens recovered from the serum of one patient had molecular weights of greater than 200,000 daltons. In rabbits, a single intravenous injection of cryptococcal capsular polysaccharides showed a similarly slow clearance of the antigen with a T1/2 of approximately 24 to 48 hours. These data suggest that adequately treated cases of cryptococcosis may have a predictable rate of antigen clearance from the serum during convalescence.
Development of Aluminum Epilayers as Buffers for GaInAs

Aluminum could be used as a structural buffer and sacrificial layer that is lattice-matched on the (001) surface to GaInAs having a 45° in-plane rotation. Conventional MOCVD from trimethylaluminum results in nanocrystalline aluminum carbide. By using hydrogen-plasma assistance in the reactor inlet, we avoid carbide formation, allowing deposition of elemental aluminum. The microstructures of these films resulting from initial applications of this method are discussed.
Nativity and Perceived Healthcare Quality

Perceptions of healthcare quality are lower among foreign- than US-born individuals. The objective of the study was to identify possible explanations for this disparity. Data were from 6202 respondents to cycles 1 and 2 of the Health Information National Trends Survey 4 conducted 2011–2013, including 5425 US-born and 777 foreign-born respondents. Perceived quality of healthcare was lower among foreign-born than US-born respondents, accounted for, to some degree (19.5 %), by foreign-born respondents experiencing relatively less patient-centered healthcare provider communication than US-born respondents. More patient-centered provider communication was associated with receiving higher quality healthcare in all respondents. Having a regular provider was associated with perceived quality of care in foreign-born but not US-born respondents, and the reverse was true for frequency of care. Patient centered provider communication and continuity of care may be key targets for improving quality of care for foreign-born individuals.
The Hidden Burden of Mental Health Outcomes Following Firearm-related Injures

Objectives:Examine the effect of different types of firearms on readmission due to acute stress disorder (ASD) and/or post-traumatic stress disorder (PTSD) in firearm-injury victims.Background:Survivors of firearm-related injuries suffer long-term sequelae such as disability, work loss, and deterior
Queer Adventures in the Forum and the Archive: Or, the Flood Made Immersion Possible:

Inspired by the Queer Archival Immersion Seminar at the Kinsey Institute during the 2017 Rhetoric Society of America (RSA) Summer Institute, this article engages the queerness of archival research ...
Nostradamus: a floorplanner of uncertain design

Floorplanning is an early phase in chip planning. It provides information on approximate area, delay, power, and other performance measures. Careful floorplanning is thus of extreme importance. In many applications while a good floorplan is needed, not all modules' information are available, or even w orse, part of the pro vided information is inaccurate. Floorplanning with uncertainty is the problem of obtaining a good floorplan under uncertainty. In this paper, the floorplanning problem with uncertainty is form ulated. It is established that traditional floorplanners are incapable of handling uncertainty. An effective method for dealing with uncertain data is proposed. Experiments sho w that, for example, with up to 30% input uncertainty an area estimate with less than 7% error can be obtained.
Analysis of methods for the Maxwell-random Lorentz model

Abstract Maxwell’s equations describes the propagation of electromagnetic fields in materials. Constitutive laws are used to describe the material response to the fields. We extend a novel computational framework involving Polynomial Chaos Expansions to the Lorentz model including random parameters. We perform stability and dispersion analyses for the resulting fully discrete schemes utilizing the second order Yee scheme in two spatial dimensions.
Stress Fractures of the Ankle and Hindfoot

Stress fractures of the ankle and hindfoot are common injuries in athletes. Most of these fractures can be treated nonoperatively, but certain factors including fracture location, vascular supply, lower leg alignment, and return to play considerations may require surgical intervention. Stress fractures of the ankle and hindfoot can also be classified as low risk and high risk in regard to propensity to heal with conservative treatment. Generally, low-risk fractures include the distal tibia, distal fibula, talus, and calcaneus. High-risk fractures include the medial malleolus and navicular. The treating health-care provider should have a low index for suspicion for stress fracture and be able to identify risk factors in regard to bone health, structural alignment, and training/competing issues in order to achieve a quick recovery and minimize the chance for recurrence of injury.
The effect of non-pharmacologic strategies on prevention or management of intensive care unit delirium: a systematic review

Background: Post-operative delirium is a common complication among adult patients in the intensive care unit. Current literature does not support the use of pharmacologic measures to manage this condition, and several studies explore the potential for the use of non-pharmacologic methods such as early mobility plans or environmental modifications. The aim of this systematic review is to examine and report on recently available literature evaluating the relationship between non-pharmacologic management strategies and the reduction of delirium in the intensive care unit. Methods: Six major research databases were systematically searched for articles analyzing the efficacy of non-pharmacologic delirium interventions in the past five years. Search results were restricted to adult human patients aged 18 years or older in the intensive care unit setting, excluding terminally ill subjects and withdrawal-related delirium. Following title, abstract, and full text review, 27 articles fulfilled the inclusion criteria and are included in this report. Results: The 27 reviewed articles consist of 12 interventions with a single-component investigational approach, and 15 with multi-component bundled protocols. Delirium incidence was the most commonly assessed outcome followed by duration. Family visitation was the most effective individual intervention while mobility interventions were the least effective. Two of the three family studies significantly reduced delirium incidence, while one in five mobility studies did the same. Multi-component bundle approaches were the most effective of all; of the reviewed studies, eight of 11 bundles significantly improved delirium incidence and seven of eight bundles decreased the duration of delirium. Conclusions: Multi-component, bundled interventions were more effective at managing intensive care unit delirium than those utilizing an approach with a single interventional element. Although better management of this condition suggests a decrease in resource burden and improvement in patient outcomes, comparative research should be performed to identify the importance of specific bundle elements.
Opioid Dependency and the Progression of Simian AIDS

Studies of the effects of opioids on T lymphocytes have become increasingly important in light of statistical data which suggest that opioid users/abusers are at high risk for developing AIDS. Also, these studies are significant since T lymphocytes play a crucial role in both cellular and humoral immunity in patients with AIDS. The simian model of immunodeficiency virus infection, which has been followed thoroughly in our laboratory in a controlled fashion, has yielded important insights which may not be obtainable from a clinical setting involving human subjects. Using this system, we have studied the consequences of chronic morphine intake on the progression of AIDS in order to model a segment of the human population shown to be at risk. These studies are concerned with the possible modulation of the immuno-responses of primates toward lentiviral as well as opioid challenges. We have found that administration of morphine sulfate to rhesus monkeys may activate the quiescent lymphocyte for proliferation, induce a transient increase in the T cell proliferative response to mitogens, and cause an enhanced interleukin-2 (IL-2) release from the mitogen-stimulated lymphocytes (1). However, longitudinal studies of the animals dependent upon morphine have revealed an overall immunosuppression of both T helper cell functions (T cell proliferation and IL-2 release) and PMN (polymorphonuclear cells) chemotaxis and phagocytosis activities (1,2). In addition to cellular effects, opioid treatment also affects the humoral response of the treated subjects; relative to saline-treated animals, morphine-dependent animals had a lower titer of anti-SIV neutralizing antibody activity after SIV infection (3).
Cities in pursuit of economic growth The local state as entrepreneur

Abstract During the past two decades, issues of local economic growth have come to dominate urban politics and planning in American cities, and local governments have adopted increasingly entrepreneurial economic-development strategies. Explanations of this by previous writers have claimed that entrepreneurial behavior by the local state is either economically determined, or stems from the initiatives of relatively autonomous political agents. In this paper it is contended that, in order to reassess these conflicting explanations, it is necessary to analyze how economic and political processes operating at different spatial scales interact to determine local policy formation and outcomes, and a conceptualization of local state action using this approach is developed. This is then applied to explain the evolution of downtown development policies in the central cities of American metropolitan areas. It is also argued that local context must be incorporated into the analysis in order to account for inter-urban variations in policy outcomes, and an abbreviated comparison of two central cities, San Francisco and Minneapolis, illustrates the importance of this.
Social purpose in a social media world

Purpose – The purpose of this paper is to illustrate the effects of social media on a company when stakeholders decide select companies are not living up to their corporate social responsibility (CSR) goals. As the number of CSR and sustainability reports on company Web sites increases, the more stakeholders, not just stockholders, know about a company’s commitment to CSR, and the more they can use social media to comment on those goals. It will describe three strategies for CSR initiatives that move beyond self-reporting of goals and progress: third party assessment, specialized certifications and partnerships to provide trustworthy data to stakeholders. Design/methodology/approach – The experiences of Nestle, Unilever, PepsiCo/Frito Lay and P & G are described. Key third-party assessors and their processes are described, as well as organizations who certify in specific areas. The importance of third-party assessment for CSR achievement is reinforced by examining the results of two reports on CSR reporti...
A Uniquely Canadian Institution: The Copyright Board of Canada

The Copyright Board of Canada, one of the first copyright administrative tribunals in the world, has moved from a simple adjucatory role to a regulatory role, adapting copyright rules to a fast-changing technological environment. Its history, role, comparative advantages and disadvantages are reviewed.
Analysis of Modulation of Immunoglobulin Gene Expression

Immunoglobulins (Ig) are critical in maintaining host immunity to a variety of pathogens. Regulation of Ig expression is a complex process involving transcriptional regulation of different Ig gene loci by many transcription factors and transcriptional regulatory regions. This complexity suggests many possible molecular targets for immunotoxicants. Therefore, thorough evaluation of chemical-induced modulation of Ig expression may necessitate multiple experimental approaches evaluating: (1) number of B cells secreting antibodies by antibody-forming cell response or plaque assay; (2) concentration of total secreted antibodies by enzyme-linked immunosorbent assay (ELISA); (3) cellular proliferation and viability by cell count measurements, [3H] thymidine incorporation, and trypan blue exclusion; (4) Ig mRNA expression by quantitative real-time reverse transcriptase–polymerase chain reaction (RT-PCR); (5) transcriptional activity of specific Ig regulatory regions by reporter gene analysis; and (6) transcription factor binding to specific Ig regulatory regions by electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP). These experimental approaches are discussed in the unit, with detailed description of EMSA, EMSA-western analysis, and isolation of nuclear protein. Curr. Protoc. Toxicol. 36:18.14.1-18.14.21. © 2008 by John Wiley & Sons, Inc. Keywords: EMSA analysis; EMSA-western analysis; supershift EMSA analysis; immunoglobulin gene; transcription factors; regulatory sequences
A simulation study for the control of a platoon of vehicles

Studies the control of the successive vehicle spacings of a platoon of vehicles traveling up hill with an incline angle. The analysis on both the identical and non-identical vehicle cases was examined. Under the steady velocity changes of the lead vehicle, the authors found that that the deviations of the vehicles from their pre-assigned positions for both cases are reasonably small and are also able to return to their steady state. The final steady state deviations of the vehicles in the platoon increase with the increase in the steepness of the hill.
Zinc absorption in human small intestine.

We determined the intestinal site of zinc absorption in humans and investigated the interaction between intestinal absorption of zinc and other solutes using the triple-lumen steady-state perfusion technique. Twenty-one healthy subjects participated in the study. During intestinal perfusion of a balanced electrolyte solution containing 0.1 mM zinc acetate, zinc absorption occurred throughout the entire small intestine. However, the jejunum had the highest rate of absorption (357 +/- 14 nM.min-1.40 cm-1) compared with the duodenum (230 +/- 33 nM.min-1.40 cm-1) and ileum (84 +/- 10 nM.min-1.40 cm-1). Over a range of zinc concentrations infused into the jejunum (0.1, 0.9, and 1.8 mM) there were linear increases in the rate of zinc absorption (P less than 0.05). Intestinal absorption of zinc was significantly stimulated by the addition of glucose (20 mM). Zinc absorption increased from 459 +/- 39 to 582 +/- 45 nM.min-1.40 cm-1 (P less than 0.05). Conversely, zinc (0.9 mM) also enhanced the absorption of glucose, which was increased from 293 +/- 43 to 447 +/- 27 microM.min-1.40 cm-1 (P less than 0.05). The enhanced absorption of zinc or glucose was not accompanied by any increase in absorption of water and sodium. In contrast, increasing the concentration of zinc in the perfusate resulted in decreased absorption of sodium and water in a dose-related manner. In conclusion, our study demonstrated that zinc absorption is concentration dependent and occurs throughout the small intestine. The jejunum has the highest rate of absorption of zinc. The interactions between absorption of zinc and other solutes suggest that the transport process of zinc is carrier mediated.
Regulation of adeno-associated virus gene expression in 293 cells: control of mRNA abundance and translation

The authors studied the effects of the adeno-associated virus (AAV) rep gene on the control of gene expression from the AAV p/sub 40/ promoter in 293 cells in the absence of an adenovirus coinfection. AAV vectors containing the chloramphenicol acetyltransferase (cat) gene were used to measure the levels of cat expression and steady-state mRNA from p/sub 40/. When the rep gene was present in cis or in trans, cat expression from p/sub 40/ was decreased 3- to 10-fold, but there was a 2- to 10-fold increase in the level of p/sub 40/ mRNA. Conversely, cat expression increased and the p/sub 40/ mRNA level decreased in the absence of the rep gene. Both wild-type and carboxyl-terminal truncated Rep proteins were capable of eliciting both effects. These data suggest two roles for the pleiotropic AAV rep gene: as a translational inhibitor and as a positive regulator of p/sub 40/ mRNA levels. They also provide additional evidence for a cis-acting negative regulatory region which decreases RNA from the AAV p/sub 5/ promoter in a fashion independent of rep.
Linking Organic Carbon, Water Content, and Nitrous Oxide Emission in a Reclaimed Coal Mine Soil

Mine-land reclamation for biomass production is often achieved by means of large applications of N and organic C with amendments that could create soil conditions favorable for N2O production and emissions. To investigate this possibility, we conducted a laboratory experiment using mine soil collected from an active surface coal mine site near Philipsburg, Pennsylvania. During a 37-d incubation period, we measured N2O and CO2 fluxes from non-amended soil and from soil amended with ammonium nitrate (L + F), composted poultry manure (Comp), poultry manure alone (Man) and mixed with 3 rates of paper mill sludge (PMS) to obtain carbon to nitrogen ratios of 14, 20 and 27 (Man + PMS14, 20 and 27), each at 60% and 80% water filled pore space (WFPS). Results showed that manure alone leads to a greater emission of N2O under laboratory conditions than with L + F. However, composting manure effectively reduced the emissions compared to that of L + F despite a large addition of organic C and N. Composted manure-treated soil emitted less than all other manure-based treatments at both 60% and 80% WFPS. The emissions were greater from soil amended with the Man + PMS treatments compared to non-amended and L + F-amended soil, and it increased during periods of intense microbial activity created by the application of manure and PMS. Higher water content increased emissions particularly during periods of intense microbial activity coupled with inorganic N availability. Cumulative N2O emissions from manure-treated soils represented less than 0·1% loss of total applied N. Copyright © 2014 John Wiley & Sons, Ltd.
Constructing densities from moments

We show how to construct distributions from moments directly, that is, without first calculating the characteristic function. We apply the method to compute the Wigner distribution from its conditional moments.
Sweet corn phosphorylase: Purification and properties☆

Abstract Sweet corn 1,4-α-glucan phosphorylase was purified 190-fold to a near homogeneous state. The enzyme had a molecular weight of about 315,000 on Sephadex G-200 chromatography. The pyridoxal 5′-phosphate content was found to 1 mole per 140,000 g protein, suggesting that the enzyme is dimeric. On sucrose density gradient ultracentrifugation the sweet corn phosphorylase was dissociated to an active monomeric species with a molecular weight of 150,000 and a sedimentation coefficient of 8 S. The priming specificity of the sweet corn phosphorylase was investigated; maltose was not a primer and maltotriose was the smallest apparent primer. The Michaelis constants for the maltosaccharide series from maltopentaose to maltooctaose were determined. The effect of d -enzyme on the apparent priming specificity of the enzyme was investigated. Adenosine diphosphoglucose and 2,3-diphosphoglycerate were found to inhibit the enzyme activity.
Adenine Recognition Is a Key Checkpoint in the Energy Release Mechanism of Phage T4 DNA Packaging Motor

ATP is the source of energy for numerous biochemical reactions in all organisms. Tailed bacteriophages use ATP to drive powerful packaging machines that translocate viral DNA into a procapsid and compact it to near-crystalline density. Here we report that a complex network of interactions dictates adenine recognition and ATP hydrolysis in the pentameric phage T4 large "terminase" (gp17) motor. The network includes residues that form hydrogen bonds at the edges of the adenine ring (Q138 and Q143), base-stacking interactions at the plane of the ring (I127 and R140), and cross-talking bonds between adenine, triphosphate, and Walker A P-loop (Y142, Q143, and R140). These interactions are conserved in other translocases such as type I/type III restriction enzymes and SF1/SF2 helicases. Perturbation of any of these interactions, even the loss of a single hydrogen bond, leads to multiple defects in motor functions. Adenine recognition is therefore a key checkpoint that ensures efficient ATP firing only when the fuel molecule is precisely engaged with the motor. This may be a common feature in the energy release mechanism of ATP-driven molecular machines that carry out numerous biomolecular reactions in biological systems.
Anomalous oxygen uptake by flowing blood.

It is found that oxygen uptake by whole blood flowing in rectangular channels greatly excedes theoretical predictions, despite the fact that such predictions are accurate when used with other channel geometries. An “optimum” rectangular channel aspect ratio for oxygen uptake improvement, relative to theory, is found and the possible use of the anomalous gas transfer in membrane oxygenator construction is indicated.
Effects of low concentrations of arachidonic acid derived mediators on the membrane potential and respiratory burst responses of human neutrophils as assessed by flow cytometry

Hypaque-Ficoll purified (95%) neutrophils (PMN) from normal healthy subjects were assessed for FMLP-elicited membrane potential (delta psi) responses and dichlorofluorescein (DCF) fluorescence (a measure of intracellular hydrogen peroxide production) using flow cytometry and appropriate fluorescent probes. Superoxide (O2) production was measured spectrophotometrically as the superoxide dismutase-inhibitable reduction of cytochrome C. The modulatory effects of dilute solutions of the arachidonic acid-derived inflammatory mediators LTB4, LTC4, LTD4, PGE1, PGE2 and PGF2 alpha (10(-9)-10(-5) M) were assessed in these systems. While LTB4 enhanced the proportion of cells depolarizing to the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP) 2-3x with a maximum effect in the 10(-9)-10(-8) M range, LTC4 and LTD4 showed no such enhancement except at high concentrations (10(-6) M). Unlike LTB4, LTC4 and LTD4 were unable to enhance FMLP mediated PMN O2 or DCF responses at any concentration tested, implying a divergence between the effects of the leukotrienes on membrane potential and oxidant responses. Pre-incubation of PMN with prostaglandins E1 or E2 led to a dose dependent inhibition of the proportion of depolarizing PMN in response to FMLP; PGF2 alpha did not show such an effect. The present data indicate that LTB4, in addition to being a powerful direct neutrophil activator, may act in a priming capacity by increasing the proportion of subsequently FMLP responsive cells, while PGE's inhibit. These modulatory effects appear relatively specific for LTB4 and the E-series prostaglandins.
Lint-Loss and Appearance-Change Tests for Blankets:

Several textile-abrasion instruments were investigated for their ability to simulate the general surface appearance and lint loss of blankets developed during laundering and actual use. An Accelerotor-type abrasion instrument was the most effective in this regard for a wide range of representative 'blanket constructions and fiber types used by consumers. A 25-second Accelerotor exposure produced simulations of blanket surface appearances comparable to those developed during use. A nomograph was produced from correlations of the lint deposited in the dryer during latindering of the blankets and lint generated by a separate, Accelerotor test. The nomograph predicts the lint deposited in the dryer per laundering from the Accelerotor lint test for all representative blanket types evaluated. This simulated performance test rapidly determines the properties that consumers readily recognize during use and care of blankets and may be useful as a basis for blanket pricing.
How musculotendon architecture and joint geometry affect the capacity of muscles to move and exert force on objects: A review with application to arm and forearm tendon transfer design

This commentary reviews musculotendon architecture and the relation between architectural parameters and the force, speed, and excursion capacity of musculotendon units. It is hoped that this review will help provide the framework within which to appreciate the importance of the data presented by Lieber et al. Muscle fiber pennation hardly affects musculotendon output of forearm and hand muscles. Instead, physiologic cross-sectional area and muscle fiber length affect force capacity and speed and excursion capacity, respectively. How muscles with equal mass can have different force, speed, and excursion capacities is explained. Since the moment arm of a muscle (the shortest distance from the musculotendon unit to the joint center of rotation) transforms muscle output into musculotendon output, it is shown why the capacity for a muscle to exert force on an object, as during grasping, is directly proportional to its moment arm and why the range of joint movement and speed over which muscles exert force is inversely proportional to the moment arm. Finally, tendon, being not stiff in forearm and hand musculotendon units, also affects their output. Criteria are given for designing tendon transfer reconstructions from architectural data and moment arm data to best replicate the biomechanical function of the replaced muscle. To have the same capacity for imparting movement to objects and exerting force on them, the donor muscle should have the same moment arm/physiologic cross-sectional area product, the same fiber length/moment arm ratio, and the same tendon length/muscle fiber length ratio as the replaced muscle.
Epigenetics and B-cell Lymphoma

Purpose of review It has only recently become apparent that mutations in epigenetic mechanisms and perturbation of epigenomic patterning are frequent events in B-cell lymphomas. The purpose of this review is to highlight these new findings and provide a conceptual framework for understanding how epigenetic modifications might contribute to lymphomagenesis. Recent findings Somatic mutations affecting histone methyltransferases such as enhancer of zeste 2 and mixed lineage leukemia 2, histone demethylases including ubiquitously transcribed X chromosome tetratricopeptide repeat and Jumonji domain-containing 2C, and histone acetyltransferases including CBP and p300 are recurrent and common in lymphomas. These mutations result in disruption of chromatin structure and functions of other proteins, ultimately causing aberrant transcriptional programming affecting multiple gene networks. Widespread perturbation of cytosine methylation patterning now appears to be a hallmark of B-cell lymphomas and occurs in specific patterns that can distinguish disease subtypes. Therapeutic targeting strategies can overcome abnormal epigenetic mechanisms and potently kill lymphoma cells. Summary Newly discovered epigenetic lesions may provide critical insights into the genesis of B-cell lymphomas, but further studies are required to understand how they affect biological mechanism. Epigenetic lesions offer tremendous opportunities for the development of improved biomarkers and treatments.
Crosslink analysis of N-terminal, C-terminal, and N/B determining regions of the Moloney murine leukemia virus capsid protein.

Abstract To analyze contacts made by Moloney murine leukemia virus (M-MuLV) capsid (CA) proteins in immature and mature virus particles, we have employed a cysteine-specific crosslinking approach that permits the identification of retroviral Gag protein interactions at particular residues. For analysis, single cysteine creation mutations were made in the context of protease-deficient or protease-competent parental constructs. Cysteine creation mutations were chosen near the N- and C-termini of CA and at a site adjacent to the M-MuLV Glu-Ala Fv1 N/B host range determination sequence. Analysis of immature virions showed that PrGag proteins were crosslinked at C-terminal CA residues to form dimers while crosslinking of particle-associated N-terminal and N/B region mutant proteins did not yield dimers, but showed evidence of linking to an unknown 140- to 160-kDa partner. Analysis of mature virions demonstrated that both N- and C-terminal CA residues participated in dimer formation, suggesting that processed CA N- and C-termini are free to establish interprotein associations. Interestingly, N/B region mutant residues in mature virus particles did not crosslink to form dimers, but showed a novel crosslinked band, consistent with an interaction between the N/B tropism determining region and a cellular protein of 45–55 kDa.
Abstract 4525: mTOR complex inhibition as a novel therapeutic strategy in high-grade papillary serous ovarian cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Objectives: To compare mTOR complex 1 inhibition (RAD001) vs. mTOR complex 1/2 inhibition (PP242) as single agents and with Carboplatin (CPP) in a preclinical model of serous ovarian cancer (OVCA). Methods: In vitro: OVCAR3 and SKOV3 cell lines were exposed to the following treatment conditions: RAD001 or PP242 as single agents, vehicle, CPP alone, and RAD001 or PP242 followed by CPP. Colony forming assays (CFAs) were performed and quantified. mRNA levels of AKT, downstream targets of mTOR and the DNA repair response (ATR, ATM, BRCA1/2) were quantified by qRTPCR. Immunoblots characterized the protein expression of key components of mTOR and DNA repair pathways. Non-parametric analyses were used to compare results across groups on SPSS. In vivo: OVCAR3 cells expressing F-Luciferase were injected IP into SCID-BG mice. 15 wks post-injection, mice were exposed to the treatment conditions described above for 4 weeks. Tumor growth and response to treatment were assessed using bioluminescence imaging (IVIS). Results were analyzed on Living Image and Prism6. Results: In vitro: OVCAR3 and SKOV3 cells are highly sensitive to mTOR inhibition. CFAs showed significantly decreased colony counts and diameter in groups exposed to either PP242 or RAD001 vs. control, an effect that was potentiated by CPP (Fig 1). qRTPCR revealed a significant decrease in 4EBP1 mRNA with mTOR inhibition (p<0.0001), but no change in other biomarkers. Although treatment with both mTOR inhibitors resulted in decreased expression of p-S6 by immunoblots, treatment with the dual inhibitor (PP242) caused a decrease in p-AKT, p-4EBP1, total and p-CHK1, and total and p-BRCA1. The levels of these proteins were not changed by addition of CPP despite the significant effect observed in the functional assay (CFA). In vivo: Treatment with CPP + PP242 was associated with a longer median survival than other treatment groups (Table 1). A decrease in tumor burden was seen on IVIS and tumor flux (photons/sec) at the end of treatment was significantly lower in mice treated with CPP+PP242 compared to other groups (p<0.0001). Conclusions: Our preclinical model supports the concurrent use of dual mTOR inhibitors and platinum chemotherapy in the treatment of OVCA. mTOR complex 1/2 inhibition impairs the DNA repair response and correlates with improved survival in a murine model. Citation Format: Fernanda Musa, Amandine Alard, Gizelka David-West, Iulia Giuroiu, Stephanie Blank, Bhavana Pothuri, John P. Curtin, Robert Schneider. mTOR complex inhibition as a novel therapeutic strategy in high-grade papillary serous ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4525. doi:10.1158/1538-7445.AM2014-4525
DNA in the core of the calf lens.

SummaryA study of DNA in the bovine lens has indicated its presence in all layers of the lens. Lenses were obtained from freshly slaughtered calves and cultured in a medium containing [3H]thymidine. The lenses were then separated into three cellular layers: epithelial, cortex and nuclear. Measurements of radioactivity of fractions from sucrose gradients of each preparation provided evidence for the presence of DNA. The radioactivity was sensitive to DNase. Apparently, pieces of DNA have been retained even in the core of the lens and these pieces can be utilized as templates by a repair enzyme (s).
Juvenile hormone activity of structurally unrelated compounds

Abstract A number of terpenoid and straight-chain alcohols and their derivatives were synthesized, purified, and their juvenile hormone activity determined, employing the Galleria bioassay. The Galleria bioassay for morphogenetic activity of juvenile hormone is described. The results indicate that (a) there is no obvious structural relationship amongst a number of compounds with high juvenile hormone activity, (b) there is a critical size of the molecule which is most active, (c) the compounds themselves have juvenile hormone activity and neither the active compounds nor their degradation products serve as precursors of juvenile hormone-mimicking substances, and (d) like the true juvenile hormone the active compounds had morphogenetic, gonadotrophic, and prothoracotrophic activities suggesting that the site and mode of action of these compounds are the same as that of the true juvenile hormone.
Dual window method for processing spectroscopic optical coherence tomography signals with simultaneously high spectral and temporal resolution

Current methods for analysis of spectroscopic optical coherence tomography (SOCT) signals suffer from an inherent tradeoff between time (depth) and frequency (wavelength) resolution. Here, we present a dual window (DW) method for reconstructing time frequency distributions (TFDs) that applies two orthogonal Gaussian windows that independently determine the spectral and temporal resolution. The effectiveness of the method is demonstrated in simulations and in processing of measured OCT signals that contain fields which vary in time and frequency. The DW method yields TFDs that maintain high spectral and temporal resolution and are free from the artifacts and limitations commonly observed with other processing methods.
On Setting Optimal Sales Commissions

This paper treats the problem of determining the commission rates a company should choose to establish for each of n products sold by a salesman. It has been shown that a sales commission plan based on paying equal commission rates on the gross margins of the salesman's product lines is optimal under the assumption that sales generated as a function of time spent on a product is a deterministic increasing function of time. This paper explores a similar problem with relaxation of the deterministic assumption. It considers a stochastic sales function in order to show differences in preference functions between a company and salesman in determining optimal commissions.
Impact of cyclin E overexpression on Smad3 activity in breast cancer cell lines

Smad3, a component of the TGFβ signaling pathway, contributes to G1 arrest in breast cancer cells. Overexpression of the cell cycle mitogen, cyclin E, is associated with poor prognosis in breast cancer, and cyclin E/CDK2 mediated phosphorylation of Smad3 has been linked with inhibition of Smad3 activity. We hypothesized that the biological aggressiveness of cyclin E overexpressing breast cancer cells would be associated with CDK2 phosphorylation and inhibition of the tumor suppressant action of Smad3. Expression constructs containing empty vector, wild-type (WT) Smad3 or Smad3 with CDK phosphorylation site mutations were co-transfected with a Smad3-responsive reporter construct into parental, vector control (A1) or cyclin E overexpressing (EL1) MCF7 cells. Smad3 function was evaluated by luciferase reporter assay and mRNA analysis. The impact of a Cdk2 inhibitor and cdk2 siRNA on Smad3 activity was also assessed. Cells expressing Smad3 containing mutations of the CDK phosphorylation sites had higher p15 and p21 and lower c-myc mRNA levels, as well as higher Smad3-responsive reporter activity, compared with controls or cells expressing WT Smad3. Transfection of cdk2 siRNA resulted in a significant increase in Smad3-responsive reporter activity compared with control siRNA; reporter activity was also increased after the treatment with a Cdk2 inhibitor. Thus, cyclin E-mediated inhibition of Smad3 is regulated by CDK2 phosphorylation of the Smad3 protein in MCF7 cells. Inhibition of CDK2 may lead to restoration of Smad3 tumor suppressor activity in breast cancer cells, and may represent a potential treatment approach for cyclin E overexpressing breast cancers.