cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 5591: A homologous recombination assay for classifying BRCA2 missense variants

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Germline mutations in BRCA2 predispose to breast, ovarian and other cancers. Although most mutations in the gene are known to be pathogenic, there is an increasing number of missense variants for which the contribution to cancer risk is unclear. These missense substitutions are referred to as VUS (variants of uncertain significance). Because loss of BRCA2 HR function leads to defective DNA double-strand break repair and an increased risk of cancer, we evaluated the utility of a cell-based Homologous Recombination (HR) assay for determination of the cancer relevance of BRCA2 VUS. Specifically, we studied VUS localized in the BRCA2 DNA binding domain (DBD) for effects on HR. We transfected full length wild-type and mutant BRCA2 constructs into V-C8 BRCA2 deficient cells along with an I-Sce1-expressing plasmid which induces an unique double strand break in an integrated DR-GFP reporter plasmid. We evaluated the ability of each BRCA2 mutant to repair the induced break by quantifying the GFP positive cells, generated by HR repair of the DNA break, with fluorescent activated cell sorting (FACS). To establish the sensitivity and specificity of the HR assay we evaluated a series of known deleterious and known neutral with the HR assay. These mutations of known effect were identified using a multifactorial likelihood approach, based on available family data, with a prior probability approach based on sequence conservation (A-GVGD) algorithm (http://agvgd.iarc.fr/agvgd_input.php). We calculated the total odds of pathogenicity for co-segregation of variants with the disease in affected carrier families, co-occurrence of VUS (in trans) with deleterious mutations and for family history of cancer of VUS and combined this odds with the A-GVGD based prior probabilities to generate the posterior probability of pathogenicity for each variant. Using this approach we successfully classified 31 VUS as either neutral or deleterious. By comparing these data with results from the HR assay we established that the assay is 100% sensitive (95% CI: 75.3% – 100%) and 100% specific (95% CI: 82.4% – 100%) for deleterious mutations in the BRCA2 DBD domain. In summary we evaluated the sensitivity and specificity of the HR assay for VUS in the DBD relative to a probability model based on family data and A-GVGD algorithm and we showed that the assay was highly sensitive and specific. Based on these results we propose that the HR assay can be used as a classifier of the clinical relevance of the VUS in the absence of direct genetic and family data. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5591. doi:10.1158/1538-7445.AM2011-5591
Building Collaboration into IDEs: Edit>Compile>Run>Debug>Collaborate?

Software development is rarely a solo coding effort. More often, it is a collaborative process, with teams of developers working together to design solutions and produce quality code. The members of these close-knit teams often look at one another’s code, collectively make plans about how to proceed, and even fix each other’s bugs when necessary. Teamwork does not stop there, however. An extended team may include project managers, testers, architects, designers, writers, and other specialists, as well as other programming teams. Programmers also interact with the community of developers outside their organization to obtain advice, code snippets, and a general understanding of what works and what doesn’t.
High-performance liquid chromatographic method for the quantification of several diamidine compounds with potential chemotherapeutic value

Abstract A high-performance liquid chromatographic method has been developed for the detection and quantification of pentamidine and pentamidine analogues of chemotherapeutic value in order to measure their concentration in physiological fluids. The compounds were extracted from urine over octadecyl solid-phase extraction columns, followed by chromatographic separation with an octadecyl reversed-phase column. For the mobile phase, a gradient of 31.5–37.5% acetonitrile in water, with sodium heptanesulfonate and tetramethylammonium chloride as ion modifiers, was used. This method was used to reliably detect levels as low as 341 ng/ml without concentration of the compounds during the solid-phase extraction. The assay was used to determine the effectiveness of several solid-phase extraction columns for isolating the compounds of interest and to quantify the amount of pentamidine and its analogues contained in the urine of dosed rats.
SMA wire actuator modular design framework

Shape memory alloy (SMA) wire actuators are quickly becoming technologically ready for a wider range of commercial applications due both to their exceptional actuation performance and to recent advances in the manufacture of drawn SMA wire. Shape memory alloys are complex materials requiring a breadth and depth of knowledge to successfully implement in more demanding industrial applications, knowledge to which most engineers may not have been exposed. This paper proposes a modular design framework to aid engineers at any level of expertise to synthesize and analyze SMA wire actuators. The modularity of the framework allows for changes in design, architecture, and system topology and allows for easy adaptation to the rapid research advances in the knowledge and understanding of the response and robust use of SMA. The layered structure of the framework is detailed; differentiating the design tasks by function: modeling, evaluation, optimization, and design guidance. Each layer is modular within itself, and in particular, the modeling layer allows for a variety of views to suit the expertise of individual designers. A sample design tool built within the framework is presented for the synthesis of actuators composed of multiple straight SMA wires acting against linear loads, accompanied by a physical system demonstration. This example, while basic, demonstrates the general applicability and flexibility of the framework for aiding many types of users in a large variety of SMA wire actuation design problems.
Alzheimer's drug design based upon an invertebrate toxin (anabaseine) which is a potent nicotinic receptor agonist

Naturally occurring toxins can often serve as useful chemical tools for investigating signalling processes in nervous and other systems. Tetrodotoxin and alpha-bungarotoxin are prime examples of toxins which are widely used in neurobiological research. Some toxins may also become molecular models for designing new drugs. Usually drugs are small, non-peptide molecules, as these display better bioavailability, longer durations of action and are less likely to generate immune responses. The relatively large size and conformational flexibility of peptides and protein toxins makes them more challenging molecular models for rational drug design. This article considers a marine invertebrate toxin, anabaseine, and describes how manipulation of the structure of this alkaloid has provided a drug candidate which selectively stimulates mammalian brain alpha7 nicotinic receptors. Numerous anabaseine analogs were synthesized and subjected to a variety of pharmacological, behavioral and toxcicological tests. This led to the choice of GTS-21 (also known as 3-(2,4-dimethoxybenzylidene)-anabaseine or DMXBA), as a drug candidate for the treatment of Alzheimer's dementia. The chemical and pharmacological properties of GTS-21 are compared with those of the initial lead compound, anabaseine.
Clicks, whistles and pulses: Passive and active signal use in dolphin communication

Abstract The search for signals out of noise is a problem not only with radio signals from the sky but in the study of animal communication. Dolphins use multiple modalities to communicate including body postures, touch, vision, and most elaborately sound. Like SETI radio signal searches, dolphin sound analysis includes the detection, recognition, analysis, and interpretation of signals. Dolphins use both passive listening and active production to communicate. Dolphins use three main types of acoustic signals: frequency modulated whistles (narrowband with harmonics), echolocation (broadband clicks) and burst pulsed sounds (packets of closely spaced broadband clicks). Dolphin sound analysis has focused on frequency-modulated whistles, yet the most commonly used signals are burst-pulsed sounds which, due to their graded and overlapping nature and bimodal inter-click interval (ICI) rates are hard to categorize. We will look at: 1) the mechanism of sound production and categories of sound types, 2) sound analysis techniques and information content, and 3) examples of lessons learned in the study of dolphin acoustics. The goal of this paper is to provide perspective on how animal communication studies might provide insight to both passive and active SETI in the larger context of searching for life signatures.
Characterization of a Passive Telemetric System for ISM Band Pressure Sensors

This paper presents a passive telemetric system for ISM band pressure sensors. The passive telemetric system is consisted of an external planar spiral coil and a pressure sensor. Theoretical analysis for the principle of the telemetric technique is described. Since the sensitivity and efficiency of the telemetric system is related with the performance of the pressure sensor and external coil. The characterization of the critical parameters for the design of pressure sensor and inductive coils are presented and analyzed separately. The characteristic impedance of the system, expressed as the function of the frequency, is measured by R&S ZVA67 VNA. The Measurement results show that the resonant frequency of the pressure sensor can shift from 397.83 to 396.84 MHz with an increasing pressure from 0 to 100 mmHg. This measurement proves the work of the telemetric system and also reflects that the ISM band pressure sensor has a high pressure sensitivity of 0.92 KHz/mmHg.
Cytoplasmic, nuclear, and golgi localization of RGS proteins. Evidence for N-terminal and RGS domain sequences as intracellular targeting motifs.

Abstract RGS proteins comprise a family of proteins named for their ability to negatively regulate heterotrimeric G protein signaling. Biochemical studies suggest that members of this protein family act as GTPase-activating proteins for certain Gα subunits, thereby accelerating the turn-off mechanism of Gα and terminating signaling by both Gα and Gβγ subunits. In the present study, we used confocal microscopy to examine the intracellular distribution of several RGS proteins in COS-7 cells expressing RGS-green fluorescent protein (GFP) fusion proteins and in cells expressing RGS proteins endogenously. RGS2 and RGS10 accumulated in the nucleus of COS-7 cells transfected with GFP constructs of these proteins. In contrast, RGS4 and RGS16 accumulated in the cytoplasm of COS-7 transfectants. As observed in COS-7 cells, RGS4 exhibited cytoplasmic localization in mouse neuroblastoma cells, and RGS10 exhibited nuclear localization in human glioma cells. Deletion or alanine substitution of an N-terminal leucine repeat motif present in both RGS4 and RGS16, a domain identified as a nuclear export sequence in HIV Rev and other proteins, promoted nuclear localization of these proteins in COS-7 cells. In agreement with this observation, treatment of mouse neuroblastoma cells with leptomycin B to inhibit nuclear protein export by exportin1 resulted in accumulation of RGS4 in the nucleus of these cells. GFP fusions of RGS domains of RGS proteins localized in the nucleus, suggesting that nuclear localization of RGS proteins results from nuclear targeting via RGS domain sequences. RGSZ, which shares with RGS-GAIP a cysteine-rich string in its N-terminal region, localized to the Golgi complex in COS-7 cells. Deletion of the N-terminal domain of RGSZ that includes the cysteine motif promoted nuclear localization of RGSZ. None of the RGS proteins examined were localized at the plasma membrane. These results demonstrate that RGS proteins localize in the nucleus, the cytoplasm, or shuttle between the nucleus and cytoplasm as nucleo-cytoplasmic shuttle proteins. RGS proteins localize differentially within cells as a result of structural differences among these proteins that do not appear to be important determinants for their G protein-regulating activities. These findings suggest involvement of RGS proteins in more complex cellular functions than currently envisioned.
Identification of arylamine N-acetyltransferase activity in the bovine lens.

Arylamine N-acetyltransferase (NAT) activity was identified and partially characterized in the bovine lens. According to size-exclusion HPLC, the molecular mass of the arylamine NAT is approximately 30-kDa. Based upon substrate specificity analysis, it is best described as an arylamine NAT which has some ability to N-acetylate arylalkylamines. This arylamine NAT acetylates para-aminobenzoic acid there by demonstrating a monomorphic pattern of N-acetylation. It demonstrates low sensitivity to methotrexate inhibition as indicated by the relatively high IC50 value (470 μM). NAT could be involved in lenticular detoxification of both endogenous amines and exogenous drugs.
Abstract A41: Effect of dietary vitamin D3 and calcium on the growth of androgeninsensitive human prostate tumor in a murine model

Abstract Vitamin D deficiency has been associated with increased risk of prostate cancer in epidemiologic and prospective studies. An association has also been made between high dietary calcium and increased prostate cancer risk. Previous studies have demonstrated that normal prostate cells and some prostate cancer cells have the ability to convert 25(OH)D to 1α,25(OH)2D. This ability along with epidemiological evidence correlating an inverse relationship between serum 25(OH)D levels and prostate cancer risk suggests that vitamin D may be important for prostate cancer prevention. The effect of dietary vitamin D and calcium on the growth of human androgen-insensitive prostate tumor in an athymic mouse model was evaluated. Three factors were considered in evaluating the role of dietary calcium and vitamin D on prostate tumor in our mice model: tumor-growth, elevation of serum calcium and overall growth of the animals (body weight). Immunohistochemical staining and Real Time PCR analysis were performed on tumors to elucidate the molecular mechanism(s) involved in vitamin D regulation of prostate cancer. Tumor-growth was highest in normal calcium, vitamin D deficient diet group (381±59 mm3) while growth in normal calcium, vitamin D sufficient (179±36 mm3), high calcium, vitamin D sufficient (199±25 mm3) and deficient (204±43 mm3) diets were not significantly different from one another. The normal calcium, vitamin D deficient diet had mice that were normo-calcemic compared to the other diet groups though there was no significant difference between groups for the weights of the animals. Proliferative (Ki67) and apoptotic (Caspase 3) staining revealed no significant difference between vitamin D sufficient and deficient diet groups. Additional staining for p21 did not show any difference among the diet groups. Gene analysis for p21, p27 and p53 did not demonstrate altered transcriptional activity in vitamin D sufficient groups. Bax and bcl-2 mRNA expression were both increased in the high calcium, vitamin D deficient diet group. The difference in tumor growth between the normal calcium, vitamin D deficient diet and the other diets suggest an important role of dietary vitamin D as a preventive agent in androgen-insensitive prostate cancer. More in vivo studies are needed to understand the molecular mechanism(s) behind vitamin D9s antitumorigenic effects. Citation Format: Rahul Ray, Mara Banks, Hilal Abuzahra, Kelly S. Persons, Vikram J. Eddy, James R. Lambert, Michael F. Holick. Effect of dietary vitamin D3 and calcium on the growth of androgeninsensitive human prostate tumor in a murine model [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A41.
Continuous monitoring of bladder and urethral pressures: new technique

A new technique for continuous monitoring of intravesical and intraurethral pressures was developed and utilized in a group of male patients to overcome the disadvantages associated with previously employed liquid and air-coupled systems. This technique permitted recording under physiologic conditions and provided information on a continuous basis concerning changes in the intravesical and intraurethral pressures in patients with multiple urologic symptoms. With further modifications this technique promises to further our understanding of the dynamics of the lower urinary tract under various conditions of stress.
Prevalence, Incidence, and Classification of Chronic Fatigue Syndrome in Olmsted County, Minnesota, as Estimated Using the Rochester Epidemiology Project

Objective To estimate the prevalence and incidence of chronic fatigue syndrome in Olmsted County, Minnesota, using the 1994 case definition and describe exclusionary and comorbid conditions observed in patients who presented for evaluation of long-standing fatigue.
Colonic histoplasmosis in acquired immunodeficiency syndrome mimicking carcinoma

Four cases of colonic histoplasmosis in patients with acquired immunodeficiency syndrome mimicking other diseases, primarily colonic adenocarcinoma, are presented. This topic has been extensively discussed from the medical and radiologic standpoint, but very few publications are found in the pathology literature. Emphasis is made on the discussion of the clinical manifestations; endoscopic, radiologic, and pathologic characteristics; differential diagnosis; and treatment.
The Role of SOCS-3 in Leptin Signaling and Leptin Resistance

We earlier demonstrated that leptin induces expression of SOCS-3 mRNA in the hypothalamus. Furthermore, transfection data suggest that SOCS-3 is an inhibitor of leptin signaling. However, little is known about the regulation of SOCS-3 expression by leptin and the mechanism by which SOCS-3 inhibits leptin action. We here show that in CHO cells stably expressing the long form of the leptin receptor (CHO-OBRl), leptin induces transient expression of endogenous SOCS-3 mRNA but not of CIS, SOCS-1, or SOCS-2 mRNA. SOCS-3 protein levels were maximal after 2-3 h of leptin treatment and remained elevated at 20 h. Furthermore, in leptin-pretreated CHO-OBRl cells, proximal leptin signaling was blocked for more than 20 h after pretreatment, thus correlating with increased SOCS-3 expression. Leptin pretreatment did not affect cell surface expression of leptin receptors as measured by (125)I-leptin binding assays. In transfected COS cells, forced expression of SOCS-3 results in inhibition of leptin-induced tyrosine phosphorylation of JAK2. Finally, JAK2 co-immunoprecipitates with SOCS-3 in lysates from leptin-treated COS cells. These results suggest that SOCS-3 is a leptin-regulated inhibitor of proximal leptin signaling in vivo. Excessive SOCS-3 activity in leptin-responsive cells is therefore a potential mechanism for leptin resistance, a characteristic feature in human obesity.
Nominal Wage Flexibility and Economic Performance: Evidence and Implications Across Industrial Countries

By considering the theoretical connection between labour and product markets, the paper evaluates the economic relationship of these markets within the contractual wage rigidity New Keynesian explanation of business cycles. The empirical analysis focuses on the short-run cyclical behaviour of real output, prices and wages for 19 industrial countries. Time-series and cross-sectional regressions are estimated. Cross-sectional cyclical correlations in the labour and goods markets are also evaluated across countries. Consistent with the theoretical predictions, aggregate uncertainty is an important factor in increasing the flexibility of the nominal wage in response to aggregate demand shocks. Wage flexibility accelerates price inflation and moderates the response of real output growth to aggregate demand shocks. Wage flexibility does not appear to be an important factor in differentiating the real and inflationary effects of energy price shocks across countries. Finally, aggregate uncertainty increases the responsiveness of output and price to productivity shocks.
Increasing demands on limited water resources: Consequences for two endangered plants in Amargosa Valley, USA.

Recent population expansion throughout the Southwest United States has created an unprecedented demand for already limited water resources, which may have severe consequences on the persistence of some species. Two such species are the federally protected Nitrophila mohavensis (Chenopodiaceae) and Grindelia fraxino-pratensis (Asteraceae) found in Amargosa Valley, one valley east of Death Valley, California. Because both species are federally protected, no plant material could be harvested for analysis. We therefore used a chamber system to collect transpired water for isotopic analysis. After a correction for isotopic en richment during transpiration, 5I80 values of plant xylem water were significantly different between N. mohavensis and G. fraxi no-pratensis throughout the study. Using a multisource mixing model, we found that both N. mohavensis and G. fraxino-pratensis used soil moisture near the soil surface in early spring when surface water was present. However, during the dry summer months, G. fraxino-pratensis tracked soil moisture to deeper depths, whereas N. mohavensis continued to use soil moisture near the soil surface. These results indicate that pumping groundwater and subsequently lowering the water table may directly prevent G. fraxino-pratensis from accessing water, whereas these same conditions may indirectly affect N. mohavensis by reducing surface soil moisture and thus its ability to access water.
Albumin microspheres for oral delivery of iron.

Bovine serum albumin (BSA) microspheres of ferric pyrophosphate (FPP) intended for passive targeting to the Peyer’s patches has been proposed for oral iron supplementation. Microspheres prepared by emulsification chemical cross linking method were characterized for surface topography, entrapment efficiency, particle size, particle charge and in vitro drug release. Microspheres of batch C with FPP to BSA ratio of 1:5 were found to be most suitable for targeting as they exhibited high entrapment (83.88 ± 4.31), high monodispersity (span = 1.24 ± 0.01), and least particle size (dvm = 4.40 ± 0.01). In addition the amount of iron retained in these microspheres despite exposure to simulated gastrointestinal conditions for 5 h was found to be 83.72 ± 4.22%, the highest in the three batches. The in vivo serum iron profiles in normal rats following oral administration displayed a reduced Tmax (2 h), elevated Cmax (106.06 ± 12.18 μg/dL) and increased AUC 0–16 h (647.44 ± 52.33 μg.h/dL) for these microspheres which ...
Calibration improves uncertainty quantification in production forecasting

Despite recent advances in uncertainty quantification, the petroleum industry continues to underestimate the uncertainties associated with reservoir production forecasts. This paper describes a calibration process that can improve quantification of uncertainties associated with reservoir performance prediction. Existing methods underestimate uncertainty because they fail to account for all, and particularly unknown, factors affecting reservoir performance and because they do not investigate all combinations of reservoir parameter values. However, the primary limitation of existing methods is that their reliability cannot be verified because the testing of an estimate of uncertainty from existing methods yields only one sample for what is inherently a statistical result. Verification and improvement of uncertainty estimates can be achieved with calibration – comparison of actual performance with previous uncertainty estimates and then using the results to scale subsequent uncertainty estimates. Calibration of uncertainty estimates can be achieved with a more frequent, if not continuous, process of data acquisition, model calibration, model prediction and uncertainty assessment, similar to the process employed in weather forecasting. Improved ability to quantify production forecast uncertainty should result in better investment decision making and, ultimately, increased profitability.
Ingestion, Digestion and Assimilation Efficiency of the Sea‐Anemone Aiptasia pallida Fed Zooplankton Prey

Ingestion time, digestion time, and assimilation efficiency by the sea anemone Aiptasia pallida were studied in the laboratory by feeding individual anemones preweighed pellets of freeze-dried Artemia salina nauplii. There was no significant correlation between anemone size, measured as dry weight, and either ingestion time, digestion time or assimilation efficiency. Similarly, there was no significant correlation between meal size (i.e., dry weight of ingested brine shrimp pellet) and either ingestion time, digestion time or assimilation efficiency. These results suggest that, under these conditions, assimilation efficiency is unaffected by either “meal” size or anemone size.
On the semiclassical limit of the focusing nonlinear Schrödinger equation

Abstract We present numerical experiments that provide new strong evidence of the existence of the semiclassical limit for the focusing nonlinear Schrodinger equation in one space dimension. Our experiments also address the spatiotemporal structure of the limit. Like in the defocusing case, the semiclassical limit appears to be characterized by sharply delimited regions of space-time containing multiphase wave microstructure. Unlike in the defocusing case, the macroscopic dynamics seem to be governed by elliptic partial differential equations. These equations can be integrated for analytic initial data, and in this connection, we interpret the caustics separating the regions of smoothly modulated microstructure as the boundaries of domains of analyticity of the solutions of the macroscopic model. For more general initial data in common function spaces, the initial value problem is ill-posed. Thus the semiclassical limit of a sequence of well-posed initial value problems is an ill-posed initial value problem.
How Population Growth Affects Linkage Disequilibrium

The "LD curve" relates the linkage disequilibrium (LD) between pairs of nucleotide sites to the distance that separates them along the chromosome. The shape of this curve reflects natural selection, admixture between populations, and the history of population size. This article derives new results about the last of these effects. When a population expands in size, the LD curve grows steeper, and this effect is especially pronounced following a bottleneck in population size. When a population shrinks, the LD curve rises but remains relatively flat. As LD converges toward a new equilibrium, its time path may not be monotonic. Following an episode of growth, for example, it declines to a low value before rising toward the new equilibrium. These changes happen at different rates for different LD statistics. They are especially slow for estimates of [Formula: see text], which therefore allow inferences about ancient population history. For the human population of Europe, these results suggest a history of population growth.
Sign ambiguity resolution for phase demodulation in interferometry with application to prelens tear film analysis

We present a novel method to solve sign ambiguity for phase demodulation from a single interferometric image that possibly contains closed fringes. The problem is formulated in a binary pairwise energy minimization framework based on phase gradient orientation continuity. The objective function is non-submodular and therefore its minimization is an NP-hard problem, for which we devise a multigrid hierarchy of quadratic pseudoboolean optimization problems that can be improved iteratively to approximate the optimal solutions. Compared with traditional path-following phase demodulation methods, the new approach does not require any heuristic scanning strategy, it is not subject to the propagation of error, and the extension to three dimensional fringe patterns is straightforward. A set of experiments with synthetic data and real prelens tear film interferometric images of the human eye demonstrate the effectiveness and robustness of the proposed algorithm in comparison with existing state-of-the-art phase demodulation methods.
Shaping Professional Development to Promote the Diffusion of Instructional Expertise Among Teachers

This study examines how high-quality professional development can promote the diffusion of effective teaching strategies among teachers through collaboration. Drawing on longitudinal and sociometri...
Properties of Sustained-Release Tablets Prepared by Hot-Melt Extrusion

The objectives of the present study were to investigate the properties of polyethylene oxide (PEO) as a drug carrier and to study the release mechanism of chlorpheniramine maleate (CPM) from matrix tablets prepared by hot-melt extrusion. During the hot-melt extrusion process, a dry powder blend of drug, polymer, and other adjuvants was fed into the extruder and melted inside the barrel of the machine. The molten mass was extruded through a rod-shaped die and then cut manually into 400-mg tablets. CPM and PEO were shown to be stable under the processing conditions. The molecular weight of the PEO, the drug loading percentage, and the inclusion of polyethylene glycol as a processing aid, were all found to influence the processing conditions and the drug release properties of the extruded tablets. Faster release of CPM from the matrix tablets was observed in acidic medium than in purified water and phosphate buffer (pH 7.4). Drug release from the matrix tablet was controlled by erosion of the PEO matrix and the diffusion of the drug through the swollen gel layer at the surface of the tablets. CPM was dispersed at the molecular level in the PEO matrix at low drug loading level and recrystallization of CPM was observed at high drug loading levels. Hot-melt extrusion was demonstrated to be a viable novel method to prepare sustained-release tablets. PEO was shown to be a suitable polymeric carrier for this process.
Antiparallel and Interlinked Control of Cellular Iron Levels by the Irr and RirA Regulators of Agrobacterium tumefaciens

The plant pathogen Agrobacterium tumefaciens encodes predicted iron-responsive regulators, Irr and RirA, that function in several other bacteria to control the response to environmental iron levels. Deletion mutations of irr and rirA, alone and in combination, were evaluated for their impact on cellular iron response. Growth was severely diminished in the Δirr mutant under iron-limiting conditions, but reversed to wild-type levels in an Δirr ΔrirA mutant. The level of uncomplexed iron in the Δirr mutant was decreased, whereas the ΔrirA mutant exhibited elevated iron levels. Sensitivity of the Δirr and ΔrirA mutants to iron-activated antimicrobial compounds generally reflected their uncomplexed-iron levels. Expression of genes that encode iron uptake systems was decreased in the Δirr mutant, whereas that of iron utilization genes was increased. Irr function required a trihistidine repeat likely to mediate interactions with heme. Iron uptake genes were derepressed in the ΔrirA mutant. In the Δirr ΔrirA mutant, iron uptake and utilization genes were derepressed, roughly combining the phenotypes of the single mutants. Siderophore production was elevated in the rirA mutant, but most strongly regulated by an RirA-controlled sigma factor. Expression of rirA itself was regulated by Irr, RirA, and iron availability, in contrast to irr expression, which was relatively stable in the different mutants. These studies suggest that in A. tumefaciens, the Irr protein is most active under low-iron conditions, inhibiting iron utilization and activating iron acquisition, while the RirA protein is active under high-iron conditions, repressing iron uptake.
Interfacial reactions between thin films of Co and InP(100)

The interfacial reactions between thin films of Co and single crystal InP have been studied. The reaction between the Co and the InP substrate already start in the as-deposited state to form In and P rich compounds. During annealing at 250{degrees}C for 30 min., phase separation takes place. In addition to unreacted Co, we find Co rich compounds, a Co-P compound in contact with the substrate, and Co-In compound in contact with the metal layer. The general morphology appears to be stable up to 500{degrees}C. At higher temperatures (500--600{degrees}C) P is released from the substrate. CoP{sub 4}, Co{sub 2}P, CoIn{sub 2} and In were detected by x-ray diffraction. At this stage the reaction is no longer uniform. 9 refs., 4 figs.
Blood pressure and cardiac output during exercise: a longitudinal study of children undergoing repair of coarctation.

Abstract Data were examined from 21 children who underwent graded exercise studies prior to and within 5 years after repair of coarctation. A control group of 10 normal children was also studied longitudinally on two occasions. The exercise was performed on an upright bicycle ergometer using a continuous graded exercise protocol. Parameters measured were heart rate, systolic and diastolic blood pressure at rest, and these pressures at the maximal voluntary exercise level. In addition, a subset of patients and controls had measurement of cardiac output by a modified acetylene rebreathing technique. Results indicate that coarctation patients had significant elevation of systolic and diastolic blood pressures at rest (p
Risk of Cardiovascular Morbidity and Mortality in Relation to Temperature

Extreme temperatures are consistently shown to have an effect on CVD-related mortality. The association between weather and CVD-related morbidity is less clear. We analyzed daily weather, ED visits classified as CVD-related based on chief complaint text, hospitalizations, and natural cause deaths that occurred in New York City. We observed lower risk of CVD-related ED visits and hospitalizations during cold and hot temperatures. The effects of extreme temperatures on CVD-related morbidity may be explained by behavioral patterns, as people are more likely to stay indoors on the coldest and hottest days.
Composition of Dietary Fiber: Neutral and Acidic Sugar Composition of the Alcohol Insoluble Residue from Human Foods

The alcohol insoluble residue (AIR) isolated from 12 foods was acid hydrolyzed and analyzed for neutral and acidic sugars. Aliquots taken at 1 hr were reduced, acetylated and analyzed for neutral sugar content with GLC. Glucose from cellulose, starch and non-cellulosic polysaccharides was analyzed with colorimetric methods. The predominant sugars present in the dietary fiber were arabinose, xylose, galactose, glucose and uronic acids. Pectin and hemicellulose together comprised the majority of cell wall polysaccharides. Samples high in starch generally contained the greatest amounts of dietary fiber and the least amount of water on a fresh plant basis.
The Holy Fool in Late Tarkovsky

This article analyzes the Russian cultural and religious phenomenon of holy foolishness (iurodstvo) in director Andrei Tarkovsky’s last two films, Nostalghia and Sacrifice. While traits of the holy fool appear in various characters throughout the director’s oeuvre, a marked change occurs in the films made outside the Soviet Union. Coincident with the films’ increasing disregard for spatiotemporal consistency and sharper eschatological focus, the character of the fool now appears to veer off into genuine insanity, albeit with a seemingly greater sensitivity to a visionary or virtual world of the spirit and explicit messianic task.
Evaluation of buffalograss germplasm for resistance to Blissus occiduus (Hemiptera: Lygaeidae).

Blissus occiduus Barber has emerged as an important insect pest of buffalograss, Buchloe ¨ dactyloides (Nuttall) Engelmann, in Nebraska. This research evaluated selected buffalograss germ- plasm for resistance to B. occiduus. Eleven buffalograss selections were screened for chinch bug resistance in three greenhouse studies and two Þeld evaluations. Based on chinch bug damage, NE91Ð118, OTatankaO, OBonnie BraeO, and OCodyO were rated highly to moderately resistant. These four buffalograsses exhibited minimal damage, even though all were heavily infested with chinch bugs. NE84-45-3 and O378O were highly susceptible to B. occiduus. Field evaluations conÞrmed chinch bug resistance ratings under Þeld conditions. NE91Ð118 displayed high levels of resistance in the Þeld screening evaluations, whereas Cody and Tatanka showed moderate levels of resistance, and 378 was highly susceptible.
Abstract 363: Urinary Free Cortisol Variations in Essential Hypertension are Associated with Altered Glucocorticoid Receptor Binding in ex vivo Human Neutrophils

The role of cortisol in essential hypertension (HTN) is yet unclear. Urinary free cortisol (UFC) levels have been shown to be bimodally distributed among hypertensives with about 30% of individuals with HTN showing high levels of UFC (high mode) and significant familial aggregation of this trait. These data suggest that UFC is a genetically determined intermediate phenotype of HTN. The mechanisms underlying this UFC variation in HTN are unknown. Prior studies have shown that despite higher UFC, the high mode group has less sodium sensitivity of blood pressure and no clinical manifestations of high cortisol, suggesting an element of glucocorticoid resistance. We evaluated the glucocorticoid receptor (GR) binding characteristics in neutrophils obtained from hypertensives with high mode versus normal/low mode UFC by immunomagnetic isolation of untouched circulating human blood cells following density gradient sedimentation with Polymorphprep. Flow cytometric analyses showed >97% of these cells were positive for CD45, CD16 and CD66B. These results were consistent with manual and automated white blood cell differential counts. Our isolation procedure produced >96% live cells as estimated by Live/Dead fluorescent viability assays. Dexamethasone (DEXA), a synthetic cortisol that binds and activates GR, showed increases in mitochondrial membrane potential but no effect on superoxide production or degranulation in these cells. In contrast, increases in superoxide production and degranulation ( P ex vivo cells were incubated with either 100nM fMLP or 10nM PMA, two well-described neutrophil activators. We determined DEXA binding parameters in neutrophils isolated from hypertensives with high mode and low mode UFC using 3 H-DEXA. Both the K d (85±16 vs 199±51 nM, n=5, P max (20.3±5 vs 61.2±20 fmol/10 6 cells, n=5, P 3 H-DEXA was displaced by >90% with RU-486, a GR antagonist. Thus our results suggest that hypertensives with high mode UFC have altered GR binding, which may drive the higher UFC levels in vivo and may have important clinical implications that warrant further investigation.
Initial Growth Mechanisms of Gold-Phosphine Clusters

Gold-phosphine cluster growth was studied at the BP86/TZV level of theory, starting from the precursor AuClPR3 (R = H, Me, and Ph), up to clusters containing four gold atoms. For all three substitu...
Hiatal hernia repair with or without esophageal lengthening: is there a difference?

ObjectiveThe need for esophageal lengthening (EL) as part of hiatal hernia (HH) repair is perceived to elevate perioperative risk and provide functionally inferior outcomes. Our objectives were to ...
Rescuing Wolves: States Not Immune to Politics

J. T. Bruskotter et al. have performed a valuable service in showing how the public trust doctrine might protect species delisted from the Endangered Species Act (ESA) or otherwise not protected (“Rescuing wolves from politics: Wildlife as a public trust resource,” Policy Forum, 30 September
Elements and Techniques to Develop a Distributed Design Framework

The direction of mechanical design is now experiencing the trends of resource globalization, design customization and demand for cheap computing. Successful integration and collaboration are very important for design systems. Currently many researches focus on client-server structure to keep the data consistent and neutral. This paper discusses the issues and techniques to build a framework to support integration and collaboration in a distributed design environment. Overview of the system architecture and modules of the framework are presented to explain the method for CAD software wrapping and management of design models. The concept of a function block module to integrate different analysis tools and a search engine to find the analysis path for design problems are also presented. A reverse engineering project is used as an example to describe how design process works in a distributed manner.Copyright © 2003 by ASME
Lagrangian formulation of spin dynamics in /sup 3/He-A

The Lagrangian formulation of spin dynamics of superfluid $^{3}\mathrm{He}$-$A$ is reexamined. The role of the anisotropic term in the spin susceptibility is clarified.
Modeling Analysis and Research of High Quality Employment Standards

Government and universities have been paid close attention to the issue of undergraduate's employment. Many factors affect the employment of college graduates, such as major, college influence, needs of the industry and students' own quality.As a result of that,some college students are still looking for jobs in order to survive.While some other college students have begun to choose high-end or high-quality employment to realize their own values. This phenomenon is called employment inequality. To solve the employment inequality problem for college students and help them in achieving high-quality employment,we need to understand what is the high-quality employment.For this reason,we analyzed several elements of high-quality employment standards first and built a high-quality standards model, and then defined the high-quality employment evaluation criteria.
Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are essential to meet LC-PUFA requirements of juvenile California Yellowtail (Seriola dorsalis)

Abstract It is likely that Seriola spp. have nutritional requirements for long-chain polyunsaturated fatty acids (LC-PUFAs) and are unable to meet physiological demand for these nutrients via biotransformation of C18 polyunsaturated fatty acids (C18 PUFAs). However, it is unclear whether 20:4n-6 (arachidonic acid, ARA), 20:5n-3 (eicosapentaenoic acid, EPA), and 22:6n-3 (docosahexaenoic acid, DHA) are each required or, as in other fish, EPA is comparatively unimportant in maintaining performance of Seriola spp. Accordingly, we assessed growth performance and tissue fatty acid composition of juvenile California Yellowtail Seriola dorsalis (formerly Seriola lalandi) fed a fish oil-based positive control diet (FISH), a soybean oil-based negative control diet (SOY), or experimental diets based on soybean oil supplemented with ARA, EPA, DHA, ARA and DHA, or all three of these fatty acids combined to achieve 50% or 100% of the concentrations typically observed in fish oil (SOY + 50% ARA, SOY + 100% ARA, SOY + 50% EPA, SOY + 100% EPA, SOY + 50% DHA, SOY + 100% DHA, SOY + 50% ARA and DHA, SOY + 100% ARA and DHA, SOY + 50% ALL, SOY + 100% ALL). As expected, fish fed the SOY diet exhibited significantly reduced growth relative to those fed the FISH diet. Supplementing with ARA alone had no effect on growth performance, and independent supplementation with EPA or DHA did not yield predictably positive effects on growth. However, fish fed the SOY + 100% ARA and DHA feed grew as well as those fed the FISH diet, and those raised on the SOY + 50% ALL and SOY + 100% ALL diets outperformed all others. Fatty acid composition of the fillet, liver, eye, and brain tissues was significantly affected by dietary treatment. As expected peripheral tissues were more modified than central tissues, and tissues of fish fed the soybean oil-based feeds exhibited higher levels of 18:2n-6 and lower levels of LC-PUFAs than those fed the rest of the experimental feeds. This effect was less overt among feeds supplemented with ARA and DHA or all three fatty acids. Results indicate that soybean oil can completely replace fish oil in California Yellowtail diets, assuming adequate levels of DHA and ARA are provided. Furthermore results illustrate the value of supplementing fish oil-free feeds with ARA, EPA, and DHA, but suggest that ARA and DHA are the primary drivers of LC-PUFA essentiality in this species. Statement of relevance The current manuscript provides valuable insights for fish nutritionists, for the aquafeed and aquaculture industries regarding fatty acid essentiality for marine carnivorous finfish. Our study supports the hypothesis that some LC-PUFAs are more physiologically important than others, with DHA and ARA being the primary drivers of fatty acid essentiality for juvenile California Yellowtail.
SU-G-TeP3-08: Pre-Clinical Radionuclide Therapy Dosimetry in Several Pediatric Cancer Xenografts

Purpose: The focus of this work is to perform Monte Carlo-based dosimetry for several pediatric cancer xenografts in mice treated with a novel radiopharmaceutical 131I-CLR1404. Methods: Four mice for each tumor cell line were injected with 8–13 µCi/g of the 124124I-CLR1404. PET/CT images of each individual mouse were acquired at 5–6 time points over the span of 96–170 hours post-injection. Following acquisition, the images were co-registered, resampled, rescaled, corrected for partial volume effects (PVE), and masked. For this work the pre-treatment PET images of 124I-CLR1404 were used to predict therapeutic doses from 131I-CLR1404 at each time point by assuming the same injection activity and accounting for the difference in physical decay rates. Tumors and normal tissues were manually contoured using anatomical and functional images. The CT and the PET images were used in the Geant4 (v9.6) Monte Carlo simulation to define the geometry and source distribution, respectively. The total cumulated absorbed dose was calculated by numerically integrating the dose-rate at each time point over all time on a voxel-by-voxel basis. Results: Spatial distributions of the absorbed dose rates and dose volume histograms as well as mean, minimum, maximum, and total dose values for each ROI were generated for each time point. Conclusion: This work demonstrates how mouse-specific MC-based dosimetry could potentially provide more accurate characterization of efficacy of novel radiopharmaceuticals in radionuclide therapy. This work is partially funded by NIH grant CA198392.
Relationship analysis: Formalizing relationships within the systems analysis process

ABSTRACTA significant aspect of the systems analysis process involves discovering and representing entities and their inter-relationships. This article presents relationship analysis (RA), a systematic, domain-independent systems analysis technique to determine a domain’s relationship structure. The quality of design artifacts, such as class diagrams, can be improved by first representing the complete relationship structure of the problem domain. A rigorous evaluation was conducted, including a formal experiment comparing novice and experienced analysts with and without the use of RA. In addition, professional software industry engineers were interviewed and educated about RA. It was shown that the RA process provides a fuller and richer systems analysis, resulting in improved quality of class diagrams. It was also shown that RA enables analysts of varying experience levels to achieve class diagrams of similar quality.