cssi/SciSciGPT-SciSciNet huggingface dataset:
FEN1 endonuclease as a therapeutic target for human cancers with defects in homologous recombination

Synthetic lethality strategies for cancer therapy exploit cancer-specific genetic defects to identify targets that are uniquely essential to the survival of tumor cells. Here we show RAD27/FEN1, which encodes flap endonuclease 1 (FEN1), a structure-specific nuclease with roles in DNA replication and repair, and has the greatest number of synthetic lethal interactions with Saccharomyces cerevisiae genome instability genes, is a druggable target for an inhibitor-based approach to kill cancers with defects in homologous recombination (HR). The vulnerability of cancers with HR defects to FEN1 loss was validated by studies showing that small-molecule FEN1 inhibitors and FEN1 small interfering RNAs (siRNAs) selectively killed BRCA1- and BRCA2-defective human cell lines. Furthermore, the differential sensitivity to FEN1 inhibition was recapitulated in mice, where a small-molecule FEN1 inhibitor reduced the growth of tumors established from drug-sensitive but not drug-resistant cancer cell lines. FEN1 inhibition induced a DNA damage response in both sensitive and resistant cell lines; however, sensitive cell lines were unable to recover and replicate DNA even when the inhibitor was removed. Although FEN1 inhibition activated caspase to higher levels in sensitive cells, this apoptotic response occurred in p53-defective cells and cell killing was not blocked by a pan-caspase inhibitor. These results suggest that FEN1 inhibitors have the potential for therapeutically targeting HR-defective cancers such as those resulting from BRCA1 and BRCA2 mutations, and other genetic defects.
Persons post-stroke improve step length symmetry by walking asymmetrically.

Restoration of step length symmetry is a common rehabilitation goal after stroke. Persons post-stroke often retain the ability to walk with symmetric step lengths (“symmetric steps”); however, the resulting walking pattern remains effortful. Two key questions with direct implications for rehabilitation have emerged: 1) how do persons post-stroke generate symmetric steps, and 2) why do symmetric steps remain so effortful? Here, we aimed to understand how persons post-stroke generate symmetric steps and explored how the resulting gait pattern may relate to the metabolic cost of transport. We recorded kinematic, kinetic, and metabolic data as nine persons post-stroke walked on an instrumented treadmill under two conditions: preferred walking and symmetric stepping (using visual feedback). Gait kinematics and kinetics remained markedly asymmetric even when persons post-stroke improved step length symmetry. Impaired paretic propulsion and aberrant movement of the center of mass were evident during both preferred walking and symmetric stepping. These deficits contributed to diminished positive work performed by the paretic limb on the center of mass in both conditions. Within each condition, decreased positive paretic work correlated with increased metabolic cost of transport and decreased walking speed across participants. It is critical to consider the mechanics used to restore symmetric steps when designing interventions to improve walking after stroke. Future research should consider the many dimensions of asymmetry in post-stroke gait, and additional within-participant manipulations of gait parameters are needed to improve our understanding of the elevated metabolic cost of walking after stroke.
FUTURE THINKING CONTINUITY OF LEARNING IN MARKETING: A STUDENT PERSPECTIVE ON CRISIS MANAGEMENT IN HIGHER EDUCATION

To boost understanding of how universities can develop strategies to ensure continuity of learning in anticipation of future crises, this research asked business students to reflect on their univer...
Resonant four-photon scattering of collinear laser pulses in plasma

Exact four-photon resonance of collinear planar laser pulses is known to be prohibited by the classical dispersion law of electromagnetic waves in plasma. We show here that the renormalization produced by an arbitrarily small relativistic electron nonlinearity removes this prohibition. The laser frequency shifts in collinear resonant four-photon scattering increase with laser intensities. For laser pulses of frequencies much greater than the electron plasma frequency, the shifts can also be much greater than the plasma frequency and even nearly double the input laser frequency at still small relativistic electron nonlinearities. This may enable broad range tunable lasers of very high frequencies and powers. Since the four-photon scattering does not rely on the Langmuir wave, which is very sensitive to plasma homogeneity, such lasers would also be able to operate at much larger plasma inhomogeneities than lasers based on stimulated Raman scattering in plasma.
Building interpersonal care teamwork skills in a virtual ipe simulation event

This is a story about the history and evolution of interprofessional education (IPE) at a mid-sized university in Michigan. It highlights an IPE simulation event conducted virtually during fall 202...
Feelings of pleasure, arousal, and dominance: men and women’s responses to athletic images in different types of sports

This experiment aimed to examine emotional responses to athletic images featuring male and female athletes in ‘gender-appropriate’, ‘gender-neutral’, and ‘gender-inappropriate’ sports. Recruiting 2...
The undercurrents of neoliberal ethics in science curricula: a critical appraisal

The world is confronted with wicked environmental problems that cannot be well understood or acted upon without addressing their ethical dimensions. Research shows that official science curricula o...
Tuning Thermal and Mechanical Properties of Polydimethylsiloxane with Carbon Fibers

In order to meet the needs of constantly advancing technologies, fabricating materials with improved properties and predictable behavior has become vital. To that end, we have prepared polydimethylsiloxane (PDMS) polymer samples filled with carbon nanofibers (CFs) at 0, 0.5, 1.0, 2.0, and 4.0 CF loadings (w/w) to investigate and optimize the amount of filler needed for fabrication with improved mechanical properties. Samples were prepared using easy, cost-efficient mechanical mixing to combine the PDMS and CF filler and were then characterized by chemical (FTIR), mechanical (hardness and tension), and physical (swelling, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and coefficient of thermal expansion) analyses to determine the material properties. We found that hardness and thermal stability increased predictably, while the ultimate strength and toughness both decreased. Repeated tension caused the CF-filled PDMS samples to lose significant toughness with increasing CF loadings. The hardness and thermal degradation temperature with 4 wt.% CF loading in PDMS increased more than 40% and 25 °C, respectively, compared with the pristine PDMS sample. Additionally, dilatometer measurements showed a 20% decrease in the coefficient of thermal expansion (CTE) with a small amount of CF filler in PDMS. In this study, we were able to show the mechanical and thermal properties of PDMS can be tuned with good confidence using CFs.
EBITDA Add-backs in Debt Contracting: A Step Too Far?

Financial covenants in syndicated loan agreements often rely on definitions of EBITDA that deviate from the GAAP definition. We document the increased usage of non-GAAP addbacks to EBITDA in recent times. Using the 2013 Interagency Guidance on Leveraged Lending, which we argue led to an exogenous increase in non-GAAP EBITDA addbacks, we show that these addbacks increase the likelihood of loan delinquency and default, and also increase the likelihood of the borrower experiencing a ratings downgrade. Greater use of non-GAAP EBITDA addbacks also makes it more likely that lead arrangers lower their loan share exposures through secondary market sales. Our results highlight that covenants based on customized measures of EBITDA hurt loan performance by worsening lead arrangers' incentives to monitor borrowers and by hampering their ability to take timely corrective actions.
Chapter 17 Medicinal Chemistry Opportunities in Bone Metabolism and Osteoporosis

Publisher Summary Recent research has aided in a substantial increase in the knowledge of basic bone metabolism. Bone is a dynamic tissue that continuously undergoes remodeling. Approximately 10% of cortical bone, the dense, mineral-rich bone that comprises the shafts of long bones, and 20%-40% of the trabecular bone, cancellous bone found in the interior of vertebrae and in the medullary space of long bones, is remodeled each year in the healthy adult. In this process, multinuclear osteoclasts resorb bone releasing mineral and matrix peptide constituents. This resorption is linked to a rebuilding process, in which osteoblasts replace eroded bone tissue. Osteoporosis (OP) is a debilitating progressive loss of bone mineral that ultimately manifests itself in elevated fracture rates, generally among those over age 45. OP is most prevalent among postmenopausal women, but affects both the sexes. Traditionally, modulation of the endocrine system has been the preferred approach to the management of OP. This chapter explains the topics in preclinical bone metabolism research as well as significant new developments in clinical management of OP. Practical in vitro and in vivo models are now available to serve as a basis for the study of synthetic mediators of bone mechanism. Thus, the development of novel therapeutic approaches to the clinical management of disease represents a significant opportunity in medicinal chemistry.
“...No one Can Hack My Mind”: Comparing Expert and Non-Expert Security Practices

The state of advice given to people today on how to stay safe online has plenty of room for improvement. Too many things are asked of them, which may be unrealistic, time consuming, or not really worth the effort. To improve the security advice, our community must find out what practices people use and what recommendations, if messaged well, are likely to bring the highest benefit while being realistic to ask of people. In this paper, we present the results of a study which aims to identify which practices people do that they consider most important at protecting their security online. We compare self-reported security practices of non-experts to those of security experts (i.e., participants who reported having five or more years of experience working in computer security). We report on the results of two online surveys—one with 231 security experts and one with 294 MTurk participants—on what the practices and attitudes of each group are. Our findings show a discrepancy between the security practices that experts and non-experts report taking. For instance, while experts most frequently report installing software updates, using two-factor authentication and using a password manager to stay safe online, non-experts report using antivirus software, visiting only known websites, and changing passwords frequently.
Quarks in nuclei

The quark model of nuclear forces is reviewed to illustrate the new perspective brought to nuclear theory by the quark structure of hadrons. The possible appearance of explicit quark effects is discussed in terms of the production of multiquark states by inelastic electron scattering and of nodal analyses of hadronhadron phase shifts.
Observations on primary short-term cultures of human tumors. A second 5-year study.

Resume Les auteurs ont etudie le comportement in vitro de 607 echantillons de tumeurs humaines, reparties en 5 grands groupes histologiques. Ils ont etabli, pour ces tumeurs, le pourcentage relatif de croissance (pourcentage de cultures positives), le temps de survie, l'activite mitotique et le degre d'incorporation de nucleosides trities. Des modalites de croissance et des types cellulaires morphologiquement definis ont ete observes. Le pourcentage relatif de croissance, en ordre decroissant, etait le suivant: 83,6% pour les lymphomes; 73,4% pour les tumeurs du systeme nerveux; 72,4% pour les carcinomes; 70,3% pour les melanomes et 65,6% pour les sarcomes. Une croissance moderee fut observee dans la majorite des lymphomes, tandis que la croissance etait lente dans la majorite des carcinomes. Les carcinomes qui avaient le plus grand pourcentage de croissance lente avaient aussi le plus petit nombre de survies des cultures apres 21 jours. Un petit nombre de survies etait egalement note dans les cas de lymphomes a croissance lente. Les lymphomes a croissance rapide avaient, par contre, un grand nombre de survies. L'activite mitotique etait tres variable parmi les divers specimens d'un meme groupe de tumeurs. L'examen des index mitotiques dans plusieurs series de cultures mit en evidence des pointes d'activite mitotique. Il y avait une coincidence remarquable entre le moment ou apparaissait ce maximum d'activite mitotique dans la culture et le temps de survie des cultures, pour les lymphomes et les carcinomes. On tenta d'etablir une relation entre l'incorporation de nucleosides marques (thymidine et uridine traitees) — temoin de la synthese d'ADN et d'ARN — et l'index mitotique. Une telle correlation ne fut observee que dans un petit nombre de cas.
INDIGENT NEGRO AND CAUCASIAN BIRTH WEIGHT-GESTATIONAL AGE TABLES

Birth weight-gestational age tables have been calculated for 7,547 indigent Caucasian and 9,800 indigent Negro deliveries. Twin pregnancies, macerated stillborn fetuses, and incomplete cases were excluded. The various collected data were tabulated by race and sex, and the 3rd, 5th, 10th, 25th, 40th, 50th, 60th, 75th, 90th, and 97th percentiles were determined. The 10th, 50th, and 90th percentiles are graphed. Ten standards for future birth weight-gestational age studies are suggested.
Radiation safety analysis for the experimental hutches at the Linac coherent light source at SLAC

The Linac Coherent Light Source (LCLS), the world's first X-ray free electron laser, will be constructed at the Stanford Linear Accelerator Center (SLAC) and is expected to be completed in 2009. A two-mirror system will be used in order to reduce background radiation in near and far experimental hutches. This paper describes the layout of the two-mirror system and also reports on the shielding requirements for the experimental hutches. Two beam loss scenarios for radiation sources are discussed: losses from the high energy electron beam hitting beam components and X-rays produced in the 130 m long undulator and scattered on X-ray mirrors. The FLUKA Monte-Carlo particle transport code was used for the shielding design and for the determination of the radiation levels around the experimental hutches.
Ground Effects on Lift for Turbofan Powered-Lift STOL Aircraft

Early studies of turbofan powered-lift STOL concepts indicated that a basic problem of aircraft which incorporate such concepts would be a serious adverse ground effect on lift. Experience to date with actual powered-lift STOL aircraft, however, has not borne out this concern. This apparent disagreement is examined and recent research data are used to help explain some of the differences observed. Analysis indicates that most of the disagreement can be attributed to the use of wind tunnel data that were not directly applicable to the airplane because the model did not properly represent some of the design features and operating conditions of the airplane.
A blueprint for automatic Boolean query processing

Conventional information retrieval systems use Boolean query formulations and inverted file technologies for search and retrieval purposes. The need to construct complex Boolean queries in order to obtain the benefit of the existing retrieval operations constitutes a substantial burden for the users. In most environments trained search intermediaries are used to facilitate the communication between system and user.In this note a new Boolean retrieval environment is outlined in which the queries are automatically constructed from the original natural language query formulations provided by the users. Any available Boolean query formulations can also be improved automatically by using the natural language text of previously retrieved documents identified as relevant during previous searches. The automatic queries can be formulated in a standard Boolean system, or in an extended system in which the interpretation of the Boolean operators and and or is relaxed. In either case. the automatic Boolean manipulations produce better retrieval output than conventional retrieval operations based on manually prepared query statements.
Designing materials for advanced microelectronic patterning applications using controlled polymerization RAFT technology

Reversible Addition Fragmentation Chain Transfer (RAFT) polymerization technology enables the production of polymers possessing low polydispersity (PD) in high yield for many applications. RAFT technology also enables control over polymer architecture. With synthetic control over these polymer characteristics, a variety of polymers can be designed and manufactured for use in advanced electronic applications. By matching the specific RAFT reagent and monomer combinations, we can accommodate monomer reactivity and optimize acrylate or methacrylate polymerizations (193 and 193i photoresist polymers) or optimize styrenic monomer systems (248 nm photoresist polymers) to yield polymers with PD as low as 1.05. For 193i lithography, we have used RAFT technology to produce block copolymers comprising of a random "resist" block with composition and size based on conventional dry photoresist materials and a "low surface energy" block The relative block lengths and compositions may be varied to tune solution migration behavior, surface energy, contact angles, and solubility in developer. Directed self assembly is proving to be an interesting and innovative method to make 2- and even 3-dimensional periodic, uniform patterns. Two keys to acceptable performance of directed self assembly from block copolymers are the uniformity and the purity of the materials will be discussed.
Exciton-exciton annihilation and the production of interchain species in conjugated polymer films: Comparing the ultrafast stimulated emission and photoluminescence dynamics of MEH-PPV

Despite the enormous versatility of conjugated polymers for use in optoelectronic devices and the correspondingly large number of research studies on their photophysics, understanding of the fundamental nature of the primary photoexcitations remains highly controversial. Part of the reason for this controversy stems from the fact that the photophysics of conjugated polymer films depends sensitively on the excitation intensity, making it difficult to compare the results of different experiments such as pump-probe stimulated emission (SE) and time-resolved photoluminescence (PL), which usually are performed at excitation intensities that differ by orders of magnitude. In this paper, we present a detailed exploration of the pump-probe SE and time-resolved PL dynamics of poly(2-methoxy 5-$[{2}^{\ensuremath{'}}$-ethylhexyloxy]-p-phenylene vinylene) (MEH-PPV) films under identical excitation conditions. Using an optically triggered streak camera, we are able to simultaneously measure the PL and SE dynamics as a function of both excitation intensity and emission wavelength. Although the SE and PL dynamics of dilute MEH-PPV solutions are identical, we find that even at relatively low excitation intensities, the PL and SE dynamics of MEH-PPV films are different, uncovering the presence of an interchain excited-state absorbing species that has dynamics distinct from the intrachain exciton. The number of interchain absorbing species increases nonlinearly with excitation intensity, suggesting that interchain species are formed both directly upon photoexcitation and as a by-product of exciton-exciton annihilation (E-EA). A comparison of the emission dynamics of pristine and intentionally oxidized MEH-PPV films leads us to conclude that there are multiple types of interchain species; we propose that the directly excited interchain species are likely aggregates or excimers, while the interchain species produced by E-EA are best assigned to polaron pairs. We also find that the wavelength dependence of the SE and PL from MEH-PPV films is complex, both because energy migration leads to a dynamic redshift of the exciton emission and because the rate of E-EA is higher for hot (blue-emitting) excitons than for thermalized (red-emitting) excitons. All the results are compared in detail to previous work, providing a means to resolve many of the apparently contradictory ideas in the literature concerning the photophysics of conjugated polymer films.
Differentiating atrioventricular nodal reentrant tachycardia from atrioventricular reentrant tachycardia by ΔHA values during entrainment from the ventricle

Background Differentiating atrioventricular nodal reentrant tachycardia (AVNRT) from orthodromic atrioventricular reentrant tachycardia (AVRT) can be difficult. The His bundle and atria are activated sequentially over the AV node during entrainment of AVNRT from the ventricle but simultaneously during supraventricular tachycardia (SVT). They are activated in parallel during entrainment of AVRT but sequentially during SVT. Objective The purpose of this study was to test the hypothesis that a ΔHA (HA(entrainment) – HA(SVT)) cutoff value of 0 reliably differentiates AVNRT from AVRT. Methods and Results Of 61 patients undergoing electrophysiologic evaluation for paroxysmal SVT, retrograde His-bundle potentials were recorded in 57 (93%) and entrainment performed in 49 (34 AVNRT, 15 AVRT). ΔHA values during entrainment from the ventricle were significantly longer during AVNRT than AVRT (31 ± 24 ms vs –38 ± 31 ms, P Conclusion The ΔHA criterion during entrainment of tachycardia from the ventricle reliably differentiates AVNRT (positive values) from AVRT (negative values).
NASA Office of Space Sciences and Applications study on Space Station attached payload pointing

A study has been conducted to determine the articulated-pointing requirements of a suite of instruments carried by the NASA Space Station, and define a pointing system architecture accomodating those requirements. It is found that these pointing requirements are sufficiently exacting, and the Space Station's disturbance environment sufficiently severe, to preclude the successful use of a conventional gimbal-pointing system; a gimbaled system incorporating an isolation stage is judged capable of furnishing the requisite levels of pointing performance.
Sample size and power calculations with correlated binary data

Correlated binary data are common in biomedical studies. Such data can be analyzed using Liang and Zeger's generalized estimating equations (GEE) approach. An attractive point of the GEE approach is that one can use a misspecified working correlation matrix, such as the working independence model (i.e., the identity matrix), and draw (asymptotically) valid statistical inference by using the so-called robust or sandwich variance estimator. In this article we derive some explicit formulas for sample size and power calculations under various common situations. The given formulas are based on using the robust variance estimator in GEE. We believe that these formulas will facilitate the practice in planning two-arm clinical trials with correlated binary outcome data.
Grid-Averaged Surface Fluxes

Abstract This study examines the inadequacies of formulations for surface fluxes for use in numerical models of atmospheric flow. The difficulty is that numerical models imply spatial averaging over each grid area. Existing formulations am based on the relationship between local fluxes and local gradients and appear to describe the relationship between the grid-averaged flux and the grid-averaged gradient poorly. For example, area-averaging the bulk aerodynamic relationship reveals additional spatial correlation terms and a complex relationship between the grid-averaged exchange coefficient and the stability based on “model” available” grid-averaged variables. This problem is studied by assuming idealized spatial distributions of the Richardson number over a grid area. Some perspective is provided by consulting observed spatial distributions of the layer Richardson number at the surface. Various contributions to the area-averaged surface flux are studied by employing a small-scale numerical model as a gri...
Molecular simulation of methane adsorption in micro- and mesoporous carbons with applications to coal and gas shale systems

Abstract Methane adsorption in porous carbon systems such as coal and the organic matrix of gas shales is an important factor in determining the feasibility of CO 2 injection for enhanced natural gas recovery and possible sequestration of CO 2 . Methane and CO 2 adsorb competitively on carbon surfaces and an understanding of each gas individually is important for determining a model to predict the feasibility of this approach for permanent CO 2 storage. Coal and gas shales have a very heterogeneous pore system, ranging from the micro, meso, and macro-scales, with the pore size strongly affecting the adsorption behavior. In micropores, the force fields of opposing pore walls are close enough that they will overlap and significantly influence the adsorption behavior, which affects adsorbate packing and density. To determine the size at which these effects become non-negligible and to determine the magnitude of this impact, grand canonical Monte Carlo simulations have been carried out to estimate the adsorption isotherms of methane across a range of pore sizes and at various temperature and pressure conditions characteristic of subsurface conditions. These isotherms have been calculated on graphitic surfaces as an initial model of coal and kerogen of gas shales. The general trend within pore sizes is that larger pores exhibit lower excess density compared to smaller pores. However, at pressure above 1 MPa, the adsorption capacities of 0.6-nm pores drop below those of the wider pores, ultimately decreasing below that of the 1.2-nm pore at 18 MPa. The density of adsorbed methane changes non-monotonically with increasing pore width, and drops to a minimum in 1.2-nm pores at 12 MPa. The isotherms have been compared with experimental data to gauge their accuracy, and the behavior of the adsorbed layer has been examined in detail. At pressures less than 2.5 MPa, the molecular simulation estimates underpredict the excess adsorption, while at pressures greater than 2.5 MPa up to 20 MPa, the simulation estimates overpredict the excess adsorption. This discrepancy is likely due to the limitation of the experimental-based model that was used to generate the pore size distribution and the surface functionalities of the porous media that were ignored in the molecular simulation investigations, but likely play an important role in determining accurate capacities under confinement at the nanoscale.
Approaching a consensus cognitive battery for clinical trials in schizophrenia: The NIMH-MATRICS conference to select cognitive domains and test criteria

To stimulate the development of new drugs for the cognitive deficits of schizophrenia, the National Institute of Mental Health (NIMH) established the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. This article presents an overview of decisions from the first MATRICS consensus conference. The goals of the meeting were to 1) identify the cognitive domains that should be represented in a consensus cognitive battery and 2) prioritize key criteria for selection of tests for the battery. Seven cognitive domains were selected based on a review of the literature and input from experts: working memory, attention/vigilance, verbal learning and memory, visual learning and memory, reasoning and problem solving, speed of processing, and social cognition. Based on discussions at this meeting, five criteria were considered essential for test selection: good test–retest reliability, high utility as a repeated measure, relationship to functional outcome, potential response to pharmacologic agents, and practicality/tolerability. The results from this meeting constitute the initial steps for reaching a consensus cognitive battery for clinical trials in schizophrenia.
Biochemical effects of the methyl ester of streptonigrin

Abstract This paper reports the biochemical effects of the methyl ester of streptonigrin on human leukemic leukocytes and erythrocytes. A qualitative and quantitative comparison was made between this drug and its parent compound, streptonigrin. Both of these quinone antitumor antibiotics catalyzed the direct oxidation of NADH and NADPH via NAD-NADP diaphorase and caused depletion of cellular ATP. As the reduced form of both drugs was autoxidized to the active state, hydrogen peroxide was formed. The impaired leukocyte protein synthesis and enhanced DNA degradation caused by these drugs were thought to be secondary to ATP depletion and peroxide formation. Although the biochemical effects of the two drugs were qualitatively similar, methyl ester streptonigrin (MeSN) was found to be considerably less effective than streptonigrin (SN). These findings in vitro correlate well with the observations that MeSN was less toxic than SN in tissue culture, animal, and man. A reduction in the biochemical effects of MeSN, as compared to SN, might explain the decreased toxicity noted with this drug. If the antitumor effects and the toxicity result from common biological mechanisms it would be predicted that MeSN would not provide a superior therapeutic ratio than its parent compound.
Initial audiologic assessment of infants referred from well baby, special care, and neonatal intensive care unit nurseries.

Purpose The purpose of the study was to evaluate the effectiveness of a 2-hr initial audiologic assessment appointment for infants referred from area universal newborn hearing screening (UNHS) prog...
SU-FF-T-162: Development of a Patient-Specific Lung Phantom Using 3D Imaging and Rapid Prototyping

Purpose: Physical human phantoms have been widely used in verification of external radiotherapytreatment plans, study of exposures outside of the target regions, and calibration of whole‐body counter for nuclear medicine procedures and for radiation safety bioassays. Existing phantoms are mostly crude in anatomical representations, although realistic 3D images of patients are available. This paper presents a method of fabricating a physical phantom of the lung using patient‐specific medical images and computer aided design (CAD) and manufacturing (CAM). Methods:Medical images have been used to construct the VIP‐Man model from Visible Human images. The voxelized data from the lung of VIP‐Man were translated into 3D polygon mesh models. The models were then corrected and scaled to the actual size of the organ. A 3D rapid prototyping machine (i.e., a 3D printer) was used to develop a physical mold of 3D polygon mesh lung. The mold was filled with lung tissue‐equivalent foam, which matched the density and effective atomic number of the lung tissue. Results: Using the methods described above the lung of the VIP‐Man model in STL format was used to fabricate an identical 3D tissue‐equivalent phantom. Conclusions: A method has been developed to rapidly prototype physical lung phantoms using CAD and CAM capabilities. Currently, there is no method that automates this complicated process of creating 3D organ phantoms. A major research effort in this task is to develop an integrated software method that will streamline image processing and 3D printing.
PGE2 Induces IL-6 in Orbital Fibroblasts through EP2 Receptors and Increased Gene Promoter Activity: Implications to Thyroid-Associated Ophthalmopathy

Background IL-6 plays an important role in the pathogenesis of Graves' disease and its orbital component, thyroid-associated ophthalmopathy (TAO). Orbital tissues become inflamed in TAO, a process in which prostanoids have been implicated. Orbital fibroblasts both generate and respond to PGE2, underlying the inflammatory phenotype of these cells. Methodology/Principal Findings Using cultured orbital and dermal fibroblasts, we characterized the effects of PGE2 on IL-6 expression. We found that the prostanoid provokes substantially greater cytokine synthesis in orbital fibroblasts, effects that are mediated through cell-surface EP2 receptors and increased steady-state IL-6 mRNA levels. The pre-translational up-regulation of IL-6 results from increased gene promoter activity and can be reproduced with the PKA agonist, Sp-cAMP and blocked by interrupting the PKA pathway. PGE2-induced production of cAMP in orbital fibroblasts was far greater than that in dermal fibroblasts, resulting from higher levels of adenylate cyclase. PGE2 provokes CREB phosphorylation, increases the pCREB/CREB ratio, and initiates nuclear localization of the pCREB/CREB binding protein/p300 complex (CBP) preferentially in orbital fibroblasts. Transfection with siRNAs targeting either CREB or CBP blunts the induction of IL-6 gene expression. PGE2 promotes the binding of pCREB to its target DNA sequence which is substantially greater in orbital fibroblasts. Conclusion/Significance These results identify the mechanism underlying the exaggerated induction of IL-6 in orbital fibroblasts and tie together two proinflammatory pathways involved in the pathogenesis of TAO. Moreover, they might therefore define an attractive therapeutic target for the treatment of TAO.
Enhancing physical activity promotion in midlife women with technology-based self-monitoring and social connectivity: A pilot study.

This pilot study tested a novel program to promote adoption and maintenance of aerobic activity in midlife women. Lifestyle modification group sessions were held weekly for 3 months, followed by two booster sessions during the 3-month maintenance phase. During all 6 months of the program, participants used a physical activity sensor to automate self-monitoring and a web platform to facilitate social connectivity. Aerobic exercise increased from 63 to 132 minute/week from baseline to 3 months (p < .01), and activity was maintained at 6 months (135 minute/week). Technology enhancements have strong potential to promote maintenance of behavior change.
Mixtec social “credit rating”—The particular versus the universal in one emic world view

Abstract That a society controls, to a greater or lesser extent, the behavior of its members is a universal; but the methods, the particulars of that control, vary from one culture to another. It is also, I would guess, a universal that in all societies people value respectability granted to them. If this is lost, the losers may become ineligible for many of the responsibilities and privileges of that society or subsociety. In this article, three ways are discussed by which such “credit rating” can be lost—as told by one member of a particular geographical subsection of the Mixtec society, as he has seen and lived it. Difficulties arose for some of its members, for example, from their refusal to vote with the majority, or from failure to care for children adequately in terms of grandparents' evaluation of the parents' responsibility, or from moral delinquency as judged by other members. Such internal cultural standards may be labeled “emic.”
Putative endogenous ligands to the benzodiazepine receptor: what can they tell us?

The endogenous ligand for the benzodiazepine receptor has not been convincingly demonstrated, nor is it clear what role this drug receptor actually plays in brain function. A number of putative endogenous ligands for the benzodiazepine receptor have been identified and reported in the literature. These putative ligands, at various stages of purification, have been typically identified by their ability to displace 3H-diazepam in a radioreceptor binding assay. Taken together, these studies provide useful information on the role that the benzodiazepine receptor and its ligand might play in brain function. The purpose of this paper is to review this area of research and attempt to provide a unifying hypothesis. In summary, calling this bioactive site the benzodiazepine receptor may be a misnomer, as it appears to effect both anxiogenic and anxiolytic activities involved in the maintenance of homeostatic levels of vigilance. Moreover, it can be suggested that endogenous ligands of reciprocal action could exist, mediating each function (relaxation and vigilance) and, thereby, maintain a balance of neural activity.
Influence of interference on photoinduced changes in transmission and reflection

Abstract The determination of photoinduced changes in the absorption coefficient (Δα) and index of refraction (Δn) from the measured changes in transmission (ΔT) and reflection (ΔR) of a thin film is discussed. It is shown that on a film with a thickness gradient special optical thicknesses can be found at which Δα is proportional to ΔT, or Δn is proportional to ΔR. The analysis is illustrated on the decays of photoinduced transmission and reflection in a-Si:H in the picosecond time domain.
ON DUPLICITY IN THE INTERVIEW

Patterns of partially blocked verbal communication are identified as duplicity, a term of Kaiser's which is here defined and applied to casework. A number of illustrative maneuvers by clients has been collected. These are here grouped according to the two proximate aims: escaping responsibility for one's words and controlling the interview. Suggestions are offered for helping the client yield these ultimately unsatisfying ways of coping with the fear of loneliness.
ENSO in a hybrid coupled model. Part I: sensitivity to physical parametrizations

A hybrid coupled model (HCM) for the tropical Pacific ocean-atmosphere system is used to test the effects of physical parametrizations on ENSO simulation. The HCM consists of the Geophysical Fluid Dynamics Laboratory ocean general circulation model coupled to an empirical atmospheric model based on the covariance matrix of observed SST and wind stress anomaly fields. In this two-part work, part I describes the effects of ocean vertical mixing schemes and atmospheric spin-up time on ENSO period. Part II addresses ENSO prediction using the HCM and examines the impact of initialization schemes. The standard version of the HCM exhibits spatial and temporal evolution that compare well to observations, with irregular cycles that tend to exhibit 3- and 4-year frequency-locking behavior. Effects in the vertical mixing parametrization that produce stronger mixing in the surface layer give a longer inherent ENSO period, suggesting model treatment of vertical mixing is crucial to the ENSO problem. Although the atmospheric spin-up time scale is short compared to ENSO time scales, it also has a significant effect in lengthening the ENSO period. This suggests that atmospheric time scales may not be truly negligible in quantitative ENSO theory. Overall, the form and evolution mechanism of the ENSO cycle is robust, even though the period is affected by these physical parametrizations.
Duodenal endoscopic findings and histopathologic confirmation of intestinal lymphangiectasia in dogs.

Background The diagnosis of intestinal lymphangiectasia (IL) has been associated with characteristic duodenal mucosal changes. However, the sensitivity and specificity of the endoscopic duodenal mucosal appearance for the diagnosis of IL are not reported. Hypothesis/Objectives To evaluate the utility of endoscopic images of the duodenum for diagnosis of IL. Endoscopic appearance of the duodenal mucosal might predict histopathologic diagnosis of IL with a high degree of sensitivity and specificity. Animals 51 dogs that underwent upper gastrointestinal (GI) endoscopy and endoscopic biopsies. Methods Retrospective review of images acquired during endoscopy. Dogs were included if adequate biopsies were obtained during upper GI endoscopy and digital images were saved during the procedure. Images were assessed for the presence and severity of IL. Using histopathology as the gold standard, the sensitivity and specificity of endoscopy for diagnosing IL were calculated. Results Intestinal lymphangiectasia (IL) was diagnosed in 25/51 dogs. Gross endoscopic appearance of the duodenal mucosa had a sensitivity and specificity (95% confidence interval) of 68% (46%, 84%) and 42% (24%, 63%), respectively for diagnosis of IL. Endoscopic images in cases with lymphopenia, hypocholesterolemia, and hypoalbuminemia had a sensitivity of 80%. Conclusions and Clinical Importance Endoscopic duodenal mucosa appearance alone lacks specificity and has only a moderate sensitivity for diagnosis of IL. Evaluation of biomarkers associated with PLE improved the sensitivity; however, poor specificity for diagnosis of IL supports the need for histopathologic confirmation.
Solution of One-Dimensional Elastic Wave Problems by the Method of Characteristics

Elastic wave problems involving one space variable solved by hyperbolic partial differential equations
Steady-state analysis of a class of carrier synchronizers†

The paper presents a steady-state analysis of the complete carrier synchronizer when the input is a non-return-to-zero (NRZ) pulse-amplitude-modulated (PAM) signal corrupted by an additive white gaussian noise. The synchronizer consists of the cascade of a bandpass filter (BPF), a non-linearity, and a phase-locked loop (PLL). The bandpass filter is assumed to be a Butterworth design and the non-linearity is of the positive power type. The variance of the phase of the regenerated carrier at the PLL output is expressed analytically as well as by a set of computer generated curves as a function of the BPF bandwidth and order, the power of the non-linearity, and the synchronizer input signal-to-noise ratio. The analysis reveals the optimum choice of the BPF, the non-linearity, and the optimum design of the PLL.
Testosterone enhances dopamine depletion by methamphetamine in male, but not female, mice

We examined the effects of varying concentrations of testosterone propionate (T) treatment within intact and gonadectomized male and female mice with regard to its capacity to alter striatal dopamine (DA) depletion in response to a neurotoxic regimen of methamphetamine (MA). Administration of T at 24h prior to MA significantly increased striatal DA depletion in intact and gonadectomized male mice. Similar treatments administered to intact and gonadectomized female mice failed to alter striatal DA concentrations in response to MA. These results demonstrate that T can enhance MA-induced neurotoxicity in male, but not in female, mice. Such findings have important implications with regard to sex differences in nigrostriatal dopaminergic function, in general, and, in specific, to sex differences related to nigrostriatal dopaminergic neurotoxicity and neurodegeneration like that in response to MA and in Parkinson's disease, where a greater incidence is typically reported for males.
A unique view on male infertility around the globe

Infertility affects an estimated 15% of couples globally, amounting to 48.5 million couples. Males are found to be solely responsible for 20-30% of infertility cases and contribute to 50% of cases overall. However, this number does not accurately represent all regions of the world. Indeed, on a global level, there is a lack of accurate statistics on rates of male infertility. Our report examines major regions of the world and reports rates of male infertility based on data on female infertility. Our search consisted of systematic reviews, meta-analyses, and population-based studies by searching the terms “epidemiology, male infertility, and prevalence.” We identified 16 articles for detailed study. We typically used the assumption that 50% of all cases of infertility are due to female factors alone, 20-30% are due to male factors alone, and the remaining 20-30% are due to a combination of male and female factors. Therefore, in regions of the world where male factor or rates of male infertility were not reported, we used this assumption to calculate general rates of male factor infertility. Our calculated data showed that the distribution of infertility due to male factor ranged from 20% to 70% and that the percentage of infertile men ranged from 2·5% to 12%. Infertility rates were highest in Africa and Central/Eastern Europe. Additionally, according to a variety of sources, rates of male infertility in North America, Australia, and Central and Eastern Europe varied from 4 5-6%, 9%, and 8-12%, respectively. This study demonstrates a novel and unique way to calculate the distribution of male infertility around the world. According to our results, at least 30 million men worldwide are infertile with the highest rates in Africa and Eastern Europe. Results indicate further research is needed regarding etiology and treatment, reduce stigma & cultural barriers, and establish a more precise calculation.
Growth factors and renal cancer: characterization and therapeutic implications

The heterogeneiety of renal-cell carcinoma can lead to unpredictable behavior: the ability to achieve a large volume yet not metastasize, the ability to demonstrate late recurrence or spontaneous regression, or the capability to metastasize at a relatively small volume. One-third of all patients who undergo radical nephrectomy for presumed localized disease will eventually have metastasis. Since renal-cell carcinoma is not significantly radio-or chemosensitive, it is important to investigate new avenues for treatment of this tumor once it has spread, specifically at the molecular level. This review discusses the most recent work on growth factors and renal cancer and proposes possible modalities for treatment.
Treatment of small nevomelanocytic nevi with a Q-switched ruby laser

Background: Small nevomelanocytic nevi are common and some are of cosmetic concern. Conventional therapy may cause a scar or permanent hypopigmentation. Objective: Our purpose was to determine whether selective photothermolysis of pigmented cells by Q-switched ruby laser treatment removes small nevomelanocytic nevi in a nonscarring fashion. Methods: Twelve patients with 18 small nevomelanocytic nevi were treated with a Q-switched ruby laser (694 nm, 28 nsec) at fluences of 8 J/cm 2 . Biopsy specimens were obtained after treatment at varying time intervals. Results: Twelve lesions (67%) showed a complete response and six lesions (33%) had a partial response. The only adverse sequela observed was mild fibrosis of the papillary dermis, without loss of papillary architecture. Conclusion: The Q-switched ruby laser is effective in removing small melanocytic nevi. However, some might recur depending on the depth of the nevomelanocytic nests.
REGULATION OF THE MEX-5 GRADIENT BY A SPATIALLY SEGREGATED KINASE/PHOSPHATASE CYCLE

Protein concentration gradients encode spatial information across cells and tissues and often depend on spatially localized protein synthesis. Here, we report that a different mechanism underlies the MEX-5 gradient. MEX-5 is an RNA-binding protein that becomes distributed in a cytoplasmic gradient along the anterior-to-posterior axis of the one-cell C. elegans embryo. We demonstrate that the MEX-5 gradient is a direct consequence of an underlying gradient in MEX-5 diffusivity. The MEX-5 diffusion gradient arises when the PAR-1 kinase stimulates the release of MEX-5 from slow-diffusive, RNA-containing complexes in the posterior cytoplasm. PAR-1 directly phosphorylates MEX-5 and is antagonized by the spatially uniform phosphatase PP2A. Mathematical modeling and in vivo observations demonstrate that spatially segregated phosphorylation and dephosphorylation reactions are sufficient to generate stable protein concentration gradients in the cytoplasm. The principles demonstrated here apply to any spatially segregated modification cycle that affects protein diffusion and do not require protein synthesis or degradation.