cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract B50: Abrogating cholesterol esterification suppresses pancreatic cancer growth and metastasis mediated by caveolin-1

Pancreatic cancer is one of the most lethal human cancers due to the lack of early diagnosis and its high propensity for metastases. Recent advances in cancer metabolism research have manifested new promises for therapy. However, cholesterol metabolism in pancreatic cancer remains poorly understood. Here, by employing label-free Raman spectromicroscopy, we found an aberrant accumulation of cholesteryl ester (CE) in human pancreatic cancer tissues and cell lines, but not in normal ones. Our biochemical study revealed that accumulation of CE is a consequence of activated PI3K/Akt/mTOR pathway. Pharmaceutical blocking and genetic knockdown of the cholesterol esterification enzyme, acyl-CoA cholesterol acyltransferase-1 (ACAT-1), reduced pancreatic cancer cell proliferation, migration and invasion rate. In an orthotopic mouse model of pancreatic cancer, ACAT-1 inhibition significantly suppressed tumor growth and metastasis. Furthermore, we showed that ACAT-1 inhibition suppressed pancreatic cancer growth and metastasis by induction of intracellular free cholesterol toxicity and down-regulation of Akt and MAPK pathway mediated by caveolin-1. Collectively, our study opens a new opportunity for treating pancreatic cancer by targeting the altered cholesterol metabolism. Citation Format: Junjie Li, Seung-Young Lee, Dongsheng Gu, Bing Song, Shaoxiong Chen, Stephen Konieczny, Timothy Ratliff, Xiaoqi Liu, Jingwu Xie, Ji-Xin Cheng. Abrogating cholesterol esterification suppresses pancreatic cancer growth and metastasis mediated by caveolin-1. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B50.
Verifying Information Flow Control over Unbounded Processes

Decentralized Information Flow Control (DIFC) systems enable programmers to express a desired DIFC policy, and to have the policy enforced via a reference monitor that restricts interactions between system objects, such as processes and files. Past research on DIFC systems focused on the reference-monitor implementation, and assumed that the desired DIFC policy is correctly specified. The focus of this paper is an automatic technique to verify that an application, plus its calls to DIFC primitives, does indeed correctly implement a desired policy. We present an abstraction that allows a model checker to reason soundly about DIFC programs that manipulate potentially unbounded sets of processes, principals, and communication channels. We implemented our approach and evaluated it on a set of real-world programs.
Hand nebulizers and asthma therapy in children and adolescents.

Should pressurized bronchodilator hand nebulizers be prescribed for routine treatment of asthma in children and adolescents? There has been considerable controversy about pressurized hand nebulizers since they were introduced into clinical medicine about 15 years ago. Proponents point to convenience, prompt relief of symptoms, and the advantage of a drug-delivery system which administers medication directly to the lungs. Others cite the danger of permitting the patient to determine his dosage of such a potent bronchodilator drug which may be packaged to deliver up to 600 dosages of medication per cartridge. Another danger is the psychological dependence which frequently results in a high abuse rate and the substitution of a nebulizer for effective oral bronchodilator therapy.
Smoothing Estimates for the Wave Equation and Applications

The purpose of this paper is to go over some recent results in analysis and partial differential equations that are related to regularity properties of solutions of the wave equation $$ \left\{ {_{u(0,x) = f(x),{\partial _t}u(0,x) = g(x).}^{\square u(t,x) = 0}} \right.$$ (1) .
América Latina: La Región más Desigual de Todas

America Latina aparece como un ejemplo nitido de una region donde los enfoques convencionales utilizados para explicar el desarrollo y los medios empleados para medirlo han sido refutados por la realidad. Esta reflexion se centra en identificar algunas dimensiones que dan cuenta de uno de los problemas mas graves vividos en los paises que integran esta region: la desigualdad. Ella se encuentra presente en todas las facetas de la vida cotidiana de sus habitantes. Se requiere con urgencia que los problemas relacionados con la desigualdad sean colocados en el centro de la discusion de la agenda publica, porque mientras ello no ocurra la desigualdad se constituira en un obstaculo para lograr un crecimiento sostenido y parametros adecuados de gobernabilidad democratica.
Dynamic assessment of quality of life after autologous bone marrow transplantation.

To determine the quality of life in adult patients after autologous bone marrow transplantation (BMT), we administered a questionnaire to a cohort of patients seen at a single referral-based center. The sample included adults 18 years and older during the 1 year following an autologous BMT. Both disease-free patients and those who relapsed with 1-year of follow-up data available were included. Of 59 eligible patients, 58 (98%) responded to the questionnaire. Patients completed a telephone questionnaire administered by a nurse specialist in the field of BMT approximately every 90 days. At the time of initial contact on day +90, the mean quality of life was 7.8 (range, 1 to 10) on a scale of 1 to 10, with 10 being the best. By the end of the first year of follow-up, the mean quality of life was 8.9 (range, 3 to 10). Seventy- eight percent of the patients were employed. Twenty-one percent lost weight during the first year, with the majority reporting voluntary weight loss. Fourteen percent reported difficulties with sexual activity. Only 5% reported difficulty with sleeping or with frequent colds. One patient felt that her appearance was worse, and none of the patients reported a poor appetite. Eighty-eight percent of surviving adult patients reported an above-average to excellent quality of life 1 year following autologous BMT. This outcome is encouraging and suggests that this procedure is not associated with long-term morbidity in the surviving adult patient.
The microvascular bed of fatty bone marrow in the adult beagle

Abstract The structure and ultrastructure of the microvascular bed of fatty bone marrow and the relationships of this vascular bed to endosteal bone surfaces was studied in adult beagles. The vascular volume of fatty bone marrow, as demonstrated by India ink-gelatin perfusion, appears less than the vascular volume of red bone marrow. The capillaries in fatty bone marrow are found between the large fat cells in a loose reticular connective tissue and have a continuous endothelial lining and basal lamina. Capillaries are frequently found adjacent to bone surfaces in these fatty marrow sites, yet are separated from these surfaces by very thin bone-lining cells. The nuclei of bone-lining cells are often found near these capillaries. The association of bone-lining cells to the microvasculature suggests that these cells may play a role in partitioning the extracellular fluids from the bone.
Computer Assisted Exposure In Scanned Film Radiography

A scanning beam system with feedback equalization is described. This offers the reduction in scattered radiation with a pair of moving slits and the regional manipulation of incident x-ray exposure to compress large variations in trans-mitted film exposure to fit within the useful exposure range of radiographic film. When applied to chest radiography, this allows maximum soft tissue contrast in the retrodiaphragmatic, retro-cardiac, mediastinal and lung field regions. The scan time to expose a 14" x 17" chest film is 5 seconds with either a one-dimensional slit scan or a two-dimensional raster scan. By manipulation of the feedback scheme, considerable variation in low frequency contrast can be obtained.© (1982) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
TERRESTRIAL SOURCES OF CARBON AND EARTHQUAKE OUTGASSING

The Earth has replenished its surface with carbon throughout geologic time. The supply may have come from hydrocarbons originally included in the body and outgassing largely through faults in the crust. Combustible gases are frequently released in earthquakes and seem to be an essential part of that phenomenon. New sources of fuel and improved earthquake prediction may come from a better understanding of the processes.
Contrasting molecular dynamics in red and purple membrane fractions of the Halobacterium halobium

2H-nuclear magnetic resonance (NMR) has been used to study the dynamics of amino acid residues in bacteriorhodopsin with results that depend on the method of sample preparation. We show here that in [2H]-leucine-labeled samples the intensity of the isotropic signal varies according to the degree of residual contamination of the sample with red membrane. We conclude that few of the surface leucine residues of bacteriorhodopsin are moving isotropically on the 2H-NMR time scale.
Immunohistochemical and ELISA Assays for Biomarkers of Oxidative Stress in Aging and Diseasea

Oxidative stress is apparent in pathology associated with aging and many age-related, chronic diseases, including atherosclerosis, diabetes mellitus, rheumatoid arthritis, and neurodegenerative diseases. Although it cannot be measured directly in biological systems, several biomarkers have been identified that provide a measure of oxidative damage to biomolecules. These include amino acid oxidation products (methionine sulfoxide, ortho-tyrosine (o-tyr) and dityrosine, chlorotyrosine and nitrotyrosine), as well as chemical modifications of protein following carbohydrate or lipid oxidation, such as N epsilon-(carboxymethyl)lysine and N epsilon-(carboxyethyl)lysine, and malondialdehyde and 4-hydroxynonenal adducts to amino acids. Other biomarkers include the amino acid cross-link pentosidine, the imidazolone adducts formed by reaction of 3-deoxyglucosone or methylglyoxal with arginine, and the imidazolium cross-links formed by the reaction of glyoxal and methylglyoxal with lysine residues in protein. These compounds have been measured in short-lived intracellular proteins, plasma proteins, long-lived extracellular proteins, and in urine, making them valuable tools for monitoring tissue-specific and systemic chemical and oxidative damage to proteins in biological systems. They are normally measured by sensitive high-performance liquid chromatography or gas chromatography-mass spectrometry methods, requiring both complex analytical instrumentation and derivatization procedures. However, sensitive immunohistochemical and ELISA assays are now available for many of these biomarkers. Immunochemical assays should facilitate studies on the role of oxidative stress in aging and chronic disease and simplify the evaluation of therapeutic approaches for limiting oxidative damage in tissues and treating pathologies associated with aging and disease. In this article we summarize recent data and conclusions based on immunohistochemical and ELISA assays, emphasizing the strengths and limitations of the techniques.
Unilateral ARMA Processes on a Square Net by the Herringbone Method

Because multidimensional ARMA processes have great potential for the simulation of geological parameters such as aquifer permeability, it was important to resolve which of two proposed alternative methods should be used for determining the two-dimensional weighting parameter, φ″, for a unilateral ARMA (1, 0) process on a square net. Practical simulations demonstrates that the correct formulation is: φ″=ρ10/(1+ρ102 where ρr,s is the correlation between lattice points at lagsr and s. When the simulations are performed with correlations of 0.8 or more a residual bias was detected which was found to be caused by a difference in the variance between the one- and two-dimensional models. This can be rectified by modifying the two- dimensional model as follows: zij=φ″(zi−1, j + zi, j−1) + λaij whereλ2=1/(1 +ρ102).
Trochaic Template Use in Early Words and Phrases

The speech of twenty normally developing children whose linguistic development spanned four MLU stages was recorded. The weak syllable productions in their spontaneous and elicited words and phrase...
The Generalised RK-Order, Orthogonality and Regular Types for Modules

I characterise various model-theoretic properties of types, in complete theories of modules, in terms of the algebraic structure of pure-injective modules. More specifically, I consider the generalised RK-order, and the relation of domination between types, orthogonality of types, and regular types. It will be seen that, essentially, it is the stationary types over pure-injective models which bear the algebraic structural information. For background in the model theory of modules, see [4], [5], [13], [17], [19], and for the model-theoretic background [10], [11], [12], [18]. More specific references will be given in the text. I summarise some principal definitions and results below. First, though, let me describe the main results. Throughout this paper, R will be a ring with 1; the language will be that for (right R -) modules. All types will be complete types in a complete theory, T , of R -modules. The notation is reserved for an extremely saturated model of T , inside which all “small” situations may be found. Thus, sets of parameters are just subsets of , and all models will be elementary substructures of . A positive primitive , or pp , formula is one which is equivalent to a formula of the form with the r ij ∈ R . Suppose that p and q are 1-types over a pure-injective model M .
Effect of pH on Sedimentation of Cod (Gadus morhua) Muscle Membranes

ABSTRACT: A new process solubilizes muscle proteins, making it possible to separate membranes with their oxidizable phospholipids, but it requires a high centrifugal force to separate the membranes. In this study we show that isolated cod muscle membranes could be readily sedimented at a low centrifugal g force for 15 min at pH 5 or below but not at pH 6 or higher. Isoelectric aggregation is likely to be responsible for the sedimentation of isolated membranes at these low pH values. Various consecutive pH treatments on isolated membranes showed that certain proteins were resolubilized or resuspended at a final pH of 10.5 if they had been previously exposed to pH 3,4, or 5. pH adjustment to 10.5 before adjustment to a pH of 5 or lower inhibited the sedimentation of isolated membranes. Isolated membranes added to the supernatant of homogenized muscle solubilized at pH 3 and centrifuged at 10000 × gfor 30 min also sedimented at 4000 × gfor 15 min. This was in contrast to the membranes naturally present in the solubilized homogenate. This suggests that factors other than viscosity were involved in the lack of efficient sedimentation of membranes from solubilized muscle tissue.
CONCERT MEDICINE : SPECTRUM OF MEDICAL PROBLEMS ENCOUNTERED AT 405 MAJOR CONCERTS

OBJECTIVES: To identify factors predictive of patient load at major commercial concert first-aid stations, and to characterize the spectrum of presenting injuries and illnesses at such events. METHODS: This study was a retrospective case series of patients presenting to on-site first-aid stations at five major concert venues in southern California over a five-year period. The authors compared the number of patients per ten thousand attendees (PPTT) with four potential predictors (music type, overall attendance, temperature, and indoor vs outdoor location) using univariate techniques and negative binomial regression. The spectrum of chief complaints observed is described. RESULTS: There were 1,492 total patients out of 4,638,099 total attendees at 405 separate concerts. The median patient load per concert was 2.1 PPTT, ranging from 0 PPTT at 53 concerts to 71 PPTT at a punk rock festival that turned into a riot. Patient load varied significantly by music category (p = 0.0001) but not with overall attendance, temperature, or indoor vs outdoor location. Median PPTT by music category ranged from 1.3 PPTT for rhythm and blues to 12.6 PPTT for gospel/Christian, with negative binomial regression indicating that rock concerts had 2.5 times (95% CI = 2.0 to 3.0) the overall patient load of non-rock concerts. Music type, however, was able to account for only 4% of the variability observed in the regression model. Trauma-related complaints predominated overall, with similar rates at rock and non-rock concerts. Four cardiac arrests occurred at classical concerts. CONCLUSION: Rock concert first-aid stations evaluated 2.5 times the patient load of non-rock concerts overall, although there was substantial concert-to-concert variability. Trauma-related complaints predominate at both rock and non-rock events. These data may assist individuals and organizations planning support for such events. Language: en
Ambiguities in the optical-model analysis of alpha-particle scattering

Abstract The phase-equivalent discrete ambiguities in the complex potential parameters which are obtained from optical-model analysis of alpha-particle elastic scattering differential cross sections are examined. A detailed analysis of the scattering of 10.8 MeV alpha particles by 24Mg is used to illustrate the discussion of these ambiguities. In principle, one technique for the reduction of the ambiguities is the coupled-equations analysis of two or more channels, and this is applied to the example data. Cluster-model information about the bound states also provides a basis for a choice. These analyses suggest that the real part of the optical-model potential for alpha particles is between 150 and 200 MeV.
Mutation rate : Some biological and biochemical considerations

Summary This article discusses ideas about the ways in which the high fidelity of DNA replication is achieved: base selection, exonucleolytic editing, and postreplicative proofreading. I also review possible mechanisms for the enhanced mutation rate associated with SOS induction. The concept of environmental control of mutation rate and other modes of genetic variation is also considered from the point of view that SOS induction is an example of « genetic revolution .
Kinetic mechanism of inhibition of the Na+-Pump and some of its partial reactions by external Na+ (Nao+)

The effects of external Na + on the activity of the Na + -pump are complex. The first-order rate constant for Na + -efflux is reduced in the presence of very low external Na + concentrations, and this inhibition is reversed when the Na + level is raised. The same pattern has been observed for Na + -ATPase activity; however, it is not apparent from the current reaction mechanisms at which site (or sites) external Na + binds to cause inhibition. In this paper, the effect of external Na + on Na + -pump activity was studied by simulation, using a model similar to the Post-Albers scheme. Curves similar to those experimentally observed were obtained assuming that: (i) after phosphorylation, three Na + ions are translocated and consecutively released to the external medium with decreasing dissociation constants; (ii) external Na + , with low affinity, binds to the K o + (external) sites stimulating dephosphorylation. These assumptions also permit one to explain the experimental observation that external Na + (with both high and low affinities) competes with K + , inhibiting the K + influx due to the Na + -pump, and the kinetically similar behavior of Na + -ATPase and ATP/ADP exchange reactions at low variable Na + concentrations. The experimental evidence available that supports the present hypothesis is discussed.
Type II pseudohypoaldosteronism. Report of a case and review of the literature.

A 56-year-old white female presented with longstanding hyperkalemia, hyperchloremia, and hypertension. Renal function was normal. Plasma renin levels were low as were serum and urinary aldosterone. Plasma Cortisol levels were normal. Fludrocortisone was ineffective in lowering serum potassium. Plasma renin and aldosterone levels responded appropriately to salt restriction and to postural changes. Plasma atrial natriuretic hormone (ANH) and urinary prostaglandins (PG) were normal. Salt loading resulted in suppression of renin and aldosterone levels and stimulation of plasma ANH and urinary PG but failed to increase potassium or chloride excretion. The persistent hyperkalemia, hyperchloremia, and suppressed renin-aldosteroneaxis were consistent with type II pseudohypoaldosteronism. Hydrochlorothiazide was effective in normalizing serum potassium levels and blood pressure. These studies exclude abnormalities in ANH and PG secretion in this disorder and are compatible with an abnormality in chloride reabsorption.
The kinetics of the gas‐phase reaction between ozone and alkenes

The rate law − d[O3]/ dt = k1[A][O3] + k3[A][O3]2/ (k4 + k5[O2]) has been found to obtain for the reaction of ozone with allene and with 1,2-butadiene. We now find that this rate law also applies to the reaction of ozone with ethylene and presumably with all lower alkenes. This generalizes the inhibiting effect of oxygen and accounts for the simplifed rate law found in the presence of excess oxygen. Oxygen itself is a product of the ozone–ethylene reaction, and we find that as [O3]0 increases, the (O2 formed)/(O3 used) ratio approaches 1.5. Values of k1, k3/k5 for ethylene are compared with those for allene, 1,3-butadiene, and propene. A generalized mechanism is postulated for the reaction of ozone with alkenes involving a chain sequence that produces oxygen and which accounts for the observed rate law. A specific mechanism is postulated for the reaction of O3 with ethylene, and the thermochemistry of the chain sequence is examined in detail.
Conceptual Framework and Issues for a Goals‐Oriented Treatment Perspective: A Commentary on “Where Do We Go From Here? The Goal Perspective in Psychotherapy”

This commentary provides an evolutionary framework for the argument that motivation—goal striving—is central to animal and human life and governs most psychological processes, with implications for clinical practice. Neglect of clients’ goals may seriously misdirect treatment; Systematic Motivational Counseling systematizes treatment of clients’ motivational structure. Treatment of the consequences and determinants of clients’ goals appears useful, as demonstrated in the case of alcohol abuse. The commentary then reexamines some currently popular goal-related concepts, particularly intrinsic versus extrinsic valuation and internality versus externality of goals, and argues for their reconceptualization on grounds that current conceptualizations have probably led to fallacious conclusions and may impair therapeutic effectiveness.
Efficient volumetric estimation from plenoptic data

The commercial release of the Lytro camera, and greater availability of plenoptic imaging systems in general, have given the image processing community cost-effective tools for light-field imaging. While this data is most commonly used to generate planar images at arbitrary focal depths, reconstruction of volumetric fields is also possible. Similarly, deconvolution is a technique that is conventionally used in planar image reconstruction, or deblurring, algorithms. However, when leveraged with the ability of a light-field camera to quickly reproduce multiple focal planes within an imaged volume, deconvolution offers a computationally efficient method of volumetric reconstruction. Related research has shown than light-field imaging systems in conjunction with tomographic reconstruction techniques are also capable of estimating the imaged volume and have been successfully applied to particle image velocimetry (PIV). However, while tomographic volumetric estimation through algorithms such as multiplicative algebraic reconstruction techniques (MART) have proven to be highly accurate, they are computationally intensive. In this paper, the reconstruction problem is shown to be solvable by deconvolution. Deconvolution offers significant improvement in computational efficiency through the use of fast Fourier transforms (FFTs) when compared to other tomographic methods. This work describes a deconvolution algorithm designed to reconstruct a 3-D particle field from simulated plenoptic data. A 3-D extension of existing 2-D FFT-based refocusing techniques is presented to further improve efficiency when computing object focal stacks and system point spread functions (PSF). Reconstruction artifacts are identified; their underlying source and methods of mitigation are explored where possible, and reconstructions of simulated particle fields are provided.
Comparison of Fourier and wavelet transform procedures for examining the mechanomyographic and electromyographic frequency domain responses during fatiguing isokinetic muscle actions of the biceps brachii.

Abstract The primary purpose of the present study was to compare the fast Fourier transform (FFT) with the discrete wavelet transform (DWT) for determining the mechanomyographic (MMG) and electromyographic (EMG) center frequency [mean power frequency (mpf), median frequency (mdf), or wavelet center frequency (cf)] patterns during fatiguing isokinetic muscle actions of the biceps brachii. Seven men (mean±SD age=23±3 years) volunteered to perform 50 consecutive maximal, concentric isokinetic muscle actions of the dominant forearm flexors at a velocity of 180°s −1 . Non-parametric "run" tests indicated significant ( p p r =0.671–0.935) and EMG ( r =0.956–0.987). Polynomial regression analyses demonstrated quadratic decreases in normalized MMG mpf ( R 2 =0.439), MMG mdf ( R 2 =0.258), MMG cf ( R 2 =0.359), EMG mpf ( R 2 =0.952), EMG mdf ( R 2 =0.914) and EMG cf ( R 2 =0.888) across repetitions. The primary finding of this study was the similarity in the mpf, mdf, and cf patterns for both MMG and EMG, which suggested that, despite the concerns over non-stationarity, Fourier based methods are acceptable for determining the patterns for normalized MMG and EMG center frequency during fatiguing dynamic muscle actions at moderate velocities.
Methane oxidation kinetics and diffusivity in soils under conventional tillage and long-term no-till

Abstract Long-term no-till (NT) farming can improve the methane (CH 4 ) oxidation capacity of agricultural soils, but the relative contribution of soil biological and physical properties on this outcome remains unclear. This understanding is especially important in fine-textured and poorly-drained soils where gas transport can limit expression of the potential for biological CH 4 oxidation. A study was conducted to assess gaseous diffusivity (D s ), CH 4 oxidation capacity (initial CH 4 : ~ 3 μL L − 1 ) and other oxidation kinetic parameters (K m , V max , T h ) in a well-drained (WD) and a poorly-drained (PD) soil under forest (WL), plow till (PT) and long-term NT (50 y). Regardless of study site, CH 4 oxidation capacity (μg CH 4 -C kg − 1 h − 1 ) was significantly higher in NT (0.26) than in PT soils (0.06), and approached (74%) the level in forest soils. Half saturation constants (K m ) and thresholds for CH 4 oxidation (T h ) were lower in NT (K m : 100.5; T h : 0.6 μL CH 4 L − 1 ) than PT soils (K m : 134; T h : 2.7 μL CH 4 L − 1 ) suggesting a shift in the affinity of methanotrophs for CH 4 in soils under long-term NT. Irrespective of soil drainage, D s was significantly higher in NT (2.97 × 10 − 3 cm 2 s − 1 ) than PT soils (1.32 × 10 − 3 cm 2 s − 1 ). CH 4 oxidation rates in intact soil cores were positively related to D s (r 2 = 0.64, P 4 oxidation. This limitation was most pronounced in the PD soils under PT (CH 4 consumption in cores was only 6% of that in sieved soils); thus, this combination of soil type and tillage would be least favorable to CH 4 uptake at the field-scale. Overall these results confirm the positive impact of NT on both the biological and physical soil attributes essential for CH 4 uptake in croplands. Long-term implementation of NT farming could therefore contribute to the mitigation of CH 4 emission from agriculture.
Dosimetric comparison of extended dose range film with ionization measurements in water and lung equivalent heterogeneous media exposed to megavoltage photons

In this study, a dosimetric evaluation of the new Kodak extended dose range (EDR) film versus ionization measurements has been conducted in homogeneous solid water and water-lung equivalent layered heterogeneous phantoms for a relevant range of field sizes (up to a field size of 25x25 cm2 and a depth of 15 cm) for 6 and 15 MV photon beams from a linear accelerator. The optical density of EDR film was found to be linear up to about 350 cGy and over-responded for larger fields and depths (5% for 25x25 cm2 at depth of 15 cm compared to a 10x10 cm2, 5 cm depth reference value). Central axis depth dose measurements in solid water with the film in a perpendicular orientation were within 2% of the Wellhofer IC-10 measurements for the smaller field sizes. A maximum discrepancy of 8.4% and 3.9% was found for the 25x25 cm2 field at 15 cm depth for 6 and 15 MV photons, respectively (with curve normalization at a depth of 5 cm). Compared to IC-10 measurements, film measured central axis depth dose inside the lung slab showed a slight over-response (at most 2%). At a depth of 15 cm in the lung phantom the over-response was found to be 7.4% and 3.7% for the 25x25 cm2 field for 6 and 15 MV photons, respectively. When results were presented as correction factors, the discrepancy between the IC-10 and the EDR was greatest for the lowest energy and the largest field size. The effect of the finite size of the ion chamber was most evident at smaller field sizes where profile differences versus film were observed in the penumbral region. These differences were reduced at larger field sizes and in situations where lateral electron transport resulted in a lateral spread of the beam, such as inside lung material. Film profiles across a lung tumor geometry phantom agreed with the IC-10 chamber within the experimental uncertainties. From this investigation EDR film appears to be a useful medium for relative dosimetry in higher dose ranges in both water and lung equivalent material for moderate field sizes and depths.
A Spatio-Temporal Deconvolution Method to Improve Perfusion CT Quantification

Perfusion imaging is a useful adjunct to anatomic imaging in numerous diagnostic and therapy-monitoring settings. One approach to perfusion imaging is to assume a convolution relationship between a local arterial input function and the tissue enhancement profile of the region of interest via a ?residue function? and subsequently solve for this residue function. This ill-posed problem is generally solved using singular-value decomposition based approaches, and the hemodynamic parameters are solved for each voxel independently. In this paper, we present a formulation which incorporates both spatial and temporal correlations, and show through simulations that this new formulation yields higher accuracy and greater robustness with respect to image noise. We also show using rectal cancer tumor images that this new formulation results in better segregation of normal and cancerous voxels.
Reward model solution methods with impulse and rate rewards: an algorithm and numerical results

Abstract Reward models have become an important method for specifying performability models for many types of systems. Many methods have been proposed for solving reward models, but no method has proven itself to be applicable over all system classes and sizes. Furthermore, specification of reward models has usually been done at the state level, which can be extremely cumbersome for realistic models. We describe a method to specify reward models as stochastic activity networks (SANs) with impulse and rate rewards, and a method by which to solve these models via uniformization. The method is an extension of one proposed by de Souza e Silva and Gail in which impulse and rate rewards are specified at the SAN level, and solved in a single model. Furthermore, we propose a new technique for discarding paths in the uniformized process whose contribution to the reward variable is minimal, which greatly reduces the time and space required for a solution. A bound is calculated on the error introduced by this discarding, and its effectiveness is illustrated through the study of the performability and availability of a degradable multi-processor system.
Three epilepsy-associated GABRG2 missense mutations at the γ +/β − interface disrupt GABAA receptor assembly and trafficking by similar mechanisms but to different extents

We compared the effects of three missense mutations in the GABAA receptor γ2 subunit on GABAA receptor assembly, trafficking and function in HEK293T cells cotransfected with α1, β2, and wildtype or mutant γ2 subunits. The mutations R82Q and P83S were identified in families with genetic epilepsy with febrile seizures plus (GEFS+), and N79S was found in a single patient with generalized tonic-clonic seizures (GTCS). Although all three mutations were located in an N-terminal loop that contributes to the γ+/β- subunit-subunit interface, we found that each mutation impaired GABAA receptor assembly to a different extent. The γ2(R82Q) and γ2(P83S) subunits had reduced α1β2γ2 receptor surface expression due to impaired assembly into pentamers, endoplasmic reticulum (ER) retention and degradation. In contrast, γ2(N79S) subunits were efficiently assembled into GABAA receptors with only minimally altered receptor trafficking, suggesting that N79S was a rare or susceptibility variant rather than an epilepsy mutation. Increased structural variability at assembly motifs was predicted by R82Q and P83S, but not N79S, substitution, suggesting that R82Q and P83S substitutions were less tolerated. Membrane proteins with missense mutations that impair folding and assembly often can be "rescued" by decreased temperatures. We coexpressed wildtype or mutant γ2 subunits with α1 and β2 subunits and found increased surface and total levels of both wildtype and mutant γ2 subunits after decreasing the incubation temperature to 30°C for 24h, suggesting that lower temperatures increased GABAA receptor stability. Thus epilepsy-associated mutations N79S, R82Q and P83S disrupted GABAA receptor assembly to different extents, an effect that could be potentially rescued by facilitating protein folding and assembly.
Differential Response of Green Algal Species to Solvents

Unicellular algae in aquatic ecosystems are subjected to a variety of pollutants from sources such as runoff from agricultural lands and industrial outfalls. Organic solvents are natural components of oil deposits and commonly find their way into surface waters as a result discharges from refineries, waste oil, disposal, and accidental spills. Organic solvents can make their way into the environment as industrial wastes. Because of their carcinogenic potential, contamination of soil and water by solvents is cause for serious concern. Relatively few reports have been published on the comparative toxicity of solvents toward test organisms, and these dealt primarily with fish and aquatic invertebrates. However, limited data of toxicity effects of solvents on algae have been published. Algae have been considered to be good indicators of bioactivity of industrial wastes. Unicellular algae vary in their response to a variety of toxicants. Little is known, however, about toxicity of solvents to freshwater unicellular green algae. The work reported here was done to examine the effect of selected solvents on unicellular green algae species to determine whether they differed in their responses to these chemicals. 14 refs., 1 fig.
Equilibration and other dynamic properties of fluids near the liquid–vapor critical point

Abstract A review is presented on the advances in understanding equilibration phenomena in compressible pure fluids near the liquid–vapor critical point. The important role of the piston effect is stressed. The equilibration of temperature and density of a fluid sample, kept in a constant volume, are described. Examples are given both above and below the critical point under Earth's gravity (1 g) and microgravity conditions. The good agreement between experimental results and simulations demonstrate the present understanding of the process. The convection onset of a compressible pure fluid in a Rayleigh–Benard cell at 1 g is described. The impact of the piston effect on the transient, which leads to damped oscillations on the way to reaching a steady state convection, is also described. Here again the results of experiments and numerical simulations are compared. To cite this article: H. Meyer, F. Zhong, C. R. Mecanique 332 (2004).
Molecular mechanisms for focal adhesion assembly through regulation of protein–protein interactions

Focal adhesions provide a useful model for studying cell/extracellular matrix interactions and the subsequent cytoskeletal reorganization. Recent advances have suggested potential mechanisms by which cells may regulate focal adhesion assembly following integrin-mediated cell adhesion.
Parametric study on the performance of a direct-expansion geothermal heat pump using carbon dioxide

Abstract A numerical model has been developed to analyze the steady state performance of a direct-expansion geothermal heat pump using carbon dioxide in a transcritical cycle. The system consists of a compressor, counter-flow gas cooler/water heater, expansion device and the ground-coupled evaporator coils. The simulation results are found to be in good agreement with the results available in the literature. To analyze the performance characteristics of carbon dioxide in the ground-coupled evaporator, the parametric study focused on evaporator parameters including coil length, number of ground circuits and mean evaporation temperature. Also investigated is the relationship between gas cooler and evaporator sizing. Results indicate that there exists an optimum number of ground circuits which results in higher heating capacity and coefficient of performance. Performance can be further improved by optimizing the mean evaporation temperature with the surrounding soil temperature. With optimization, the system under study could achieve a coefficient of performance of 2.58, representing an 18% improvement compared to the baseline system.
Prevalence and correlates of elevated body mass index among HIV-positive and HIV-negative women in the women's interagency HIV study

Since the introduction of highly active antiretroviral therapy (HAART) and the subsequent increased life expectancy in HIV-infected persons, non-HIV-related diseases have become an important cause of morbidity and mortality. This cross-sectional study reports the prevalence of overweight and obesity, and sociodemographic, psychological, and substance use-related risk factors for elevated body mass index (BMI) among 2157 HIV-seropositive (HIV+) in comparison to 730 HIV-seronegative (HIV-) participants in the Women's Interagency HIV Study (WIHS). Separate univariable and multivariate linear regression analyses were completed for HIV+ and HIV- women. Our study revealed a similar proportion of obesity (body mass index [BMI] >or=30) among HIV+ (33%) and HIV- women (29%) (p = 0.12), as well as comparable median BMI (HIV+: 26.1 versus HIV-: 26.7, p = 0.16). HIV+ compared to HIV- women, respectively, were significantly (p < 0.01) older (median = 35.6 versus. 32.5), but similar (p = 0.97) by race/ethnicity (57% African American, 28% Hispanic, and 15% white for both). In multivariate models for both HIV+ and HIV- women, African American race/ethnicity was significantly (p < 0.05) associated with higher BMI, while higher quality of life score and illicit hard drug use were associated with lower BMI. Additionally, smoking, alcohol use, markers of advanced HIV infection (AIDS diagnosis, elevated HIV viral load, low CD4 count), and a history of antiretroviral therapy use (ART) were also associated with lower BMI among HIV+ women. In conclusion, risk factors for elevated BMI were similar for HIV+ and HIV- women in the WIHS. For HIV+ women, all markers of advanced HIV infection and ART use were additionally associated with lower BMI.
The psychology of the pair-bond: Past and future contributions of close relationships research to evolutionary psychology.

Stewart-Williams and Thomas (this issue) urge evolutionary psychologists to reconsider their historically heavy emphasis on sex differences in human mating. The authors draw from research in biolog...
Preserving properties of object shape by computations in primary visual cortex

Although our visual system is extremely good at extracting objects from the visual scene, this process involves complicated computations that are thought to require image processing by many successive cortical areas. Thus, intermediate stages in object extraction should not eliminate essential properties of the objects that are still required by later stages. A particularly important characteristic of an object is its shape, and shape has the property that it is unchanged by translations, rotations, and magnifications of the image. I show that the requirement for this property of shape to be preserved in the image, as represented by the firing of neurons in the primary visual cortex (V1), is equivalent to a particular type of computation, known as a wavelet transform, determining the firing rate of V1 neurons in response to an image on the retina. Experimental data support the conclusion that the neural representation of images in V1 is described by a wavelet transform and, therefore, that the properties of shape are preserved.
Low Frequency Variants, Collapsed Based on Biological Knowledge, Uncover Complexity of Population Stratification in 1000 Genomes Project Data

Analyses investigating low frequency variants have the potential for explaining additional genetic heritability of many complex human traits. However, the natural frequencies of rare variation between human populations strongly confound genetic analyses. We have applied a novel collapsing method to identify biological features with low frequency variant burden differences in thirteen populations sequenced by the 1000 Genomes Project. Our flexible collapsing tool utilizes expert biological knowledge from multiple publicly available database sources to direct feature selection. Variants were collapsed according to genetically driven features, such as evolutionary conserved regions, regulatory regions genes, and pathways. We have conducted an extensive comparison of low frequency variant burden differences (MAF<0.03) between populations from 1000 Genomes Project Phase I data. We found that on average 26.87% of gene bins, 35.47% of intergenic bins, 42.85% of pathway bins, 14.86% of ORegAnno regulatory bins, and 5.97% of evolutionary conserved regions show statistically significant differences in low frequency variant burden across populations from the 1000 Genomes Project. The proportion of bins with significant differences in low frequency burden depends on the ancestral similarity of the two populations compared and types of features tested. Even closely related populations had notable differences in low frequency burden, but fewer differences than populations from different continents. Furthermore, conserved or functionally relevant regions had fewer significant differences in low frequency burden than regions under less evolutionary constraint. This degree of low frequency variant differentiation across diverse populations and feature elements highlights the critical importance of considering population stratification in the new era of DNA sequencing and low frequency variant genomic analyses.
Thomas Jefferson and John Marshall: What Kind of Constitution Shall We Have?

Although they were third cousins once removed—both descended from William Randolph of Turkey Island, one of the first settlers in Virginia—John Marshall and Thomas Jefferson had little familial affection for one another. During the disputed contest of 1800, the future Chief Justice felt “almost insuperable objection” to the man who eventually become the third President, declaring him “totally unfit for the chief magistracy of a nation which cannot indulge these prejudices without sustaining deep personal injury.”1 For his part, Jefferson reciprocated, and his cousin became the embodiment of all he despised in the judiciary. He wrote of Marshall as a man of “lax lounging manners … and a profound hypocrisy.”2
Treatment of intestinal failure: intestinal transplantation

Over the past 15 years, intestinal transplantation for the treatment of intestinal failure has changed from a desperate last-ditch effort into a standard therapy for which a good outcome is expected. In this Review, the author considers several issues surrounding intestinal transplantation, including patient selection, allograft type, outcomes, complications, post-transplant monitoring and cost.
Abstract 4902: Low dose Ganetespib (STA-9090) enhances radiotherapy effects on lung cancer cells by synergistically altering levels of cell cycle progression proteins

Radiotherapy is an important component for the curative management of locally advanced non-small cell lung cancer (LA-NSCLC); however radioresistance can hamper the efficacy of treatment. Biological innovations by combining molecular targeted therapy with radiation could potentially enhance radiotherapy efficacy. Hsp90 (heat shock protein 90) is a chaperone protein that assists other proteins in folding, stability and degradation. Since Hsp90 stabilizes a variety of client proteins required for survival of cancer cells, Hsp90 inhibitors are currently studied for their therapeutic benefit in the treatment of various types of malignancies. One drug in particular is Ganetespib, a potent second generation HSP90 inhibitor with minimal ocular and hepatic toxicities, has proven improved efficacy in Stage IV NSCLC in combination with docetaxel, and is now in phase III clinical testing (GALAXY-II). The purpose of our study is to determine if low dose (25 nM) Ganetespib in combination with irradiation can enhance the radiotherapeutic effects on human lung cancer cells. The experiments were conducted using Kras mutant H460 and A549 cells, and Kras wild type H1650 cells with p53 mutation. Cell survival was measured by clonogenic survival assay (CSA). Cell cycle distribution was analyzed by flow cytometry. Expression and activity of radiosensitivity related proteins was investigated by RPPA and western blotting. Our results demonstrated that Ganetespib reduced radiation clonogenic survival on lung cancer cells, and greatly attenuated DNA damage repair with irradiation as assessed by P53BP1 foci formation. Cell cycle analysis showed that Ganetespib dramatically increased G2/M arrest between 24-48 hours, which placed cells in the radiosensitive part of the cell cycle, thereby promoting subsequent apoptosis after 48 hours. On RPPA, while higher doses of Ganetespib (50-100 nM) completely attenuated the expression of important client growth factor and survival promoting proteins such as EGFR, Her-2, AKT, and mTOR, and enhanced expressed of apoptotic pathways proteins, radiation dose-dependently acted in concert with low dose Ganetespib to upregulate p21 and downregulate pRb levels that were not apparent with either drug or radiation alone. These results suggest that low dose Ganetespib can act as a potent radiosensitizer in the treatment of NSCLC by altering levels of cell cycle progression proteins. Ganetespib in combination with radiotherapy should be explored clinically in LA-NSCLC. Citation Format: Hui Liu, Adam Potter, Jingya Wang, Uma Giri, Steven H. Lin. Low dose Ganetespib (STA-9090) enhances radiotherapy effects on lung cancer cells by synergistically altering levels of cell cycle progression proteins. [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 4902. doi:10.1158/1538-7445.AM2014-4902