cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of prolonged chemical treatment with cyclophosphamide and 6-mercaptopurine in the dominant lethal test system.

Abstract The effects of prolonged chemical treatment with cyclophosphamide and 6-mercaptopurine were investigated in the dominant lethal test system. Groups of 15 male Holtzman rats were given 5 daily i.p. injections of the compounds per week for 10 weeks; dose levels were 0 (water), 5.0, 10.0 and 20.0 mg/kg in the cyclophosphamide study and 0 (dimethylsulfoxide), 12.5, 25.0 and 50.0 mg/kg in the 6-mercaptopurine study. Each study also contained a group given i.p. injections of triethylenemelamine (0.025 mg/kg), the positive control compound, which was diluted in water. After the final injection, each male rat was housed with 2 virgin females per week for 2 weeks. Females were killed 14 days from the midweek of cohousing and uterine contents were examined to evaluate the numbers of total implants, dead implants, dead implants per total implants and females with 1 or more, or 2 or more, dead implants. Results from the cyclophosphamide study indicated a positive dominant lethal effect in both weeks of mating. Negative results were obtained for all levels of 6-mercaptopurine treatment for both weeks, with the exception of 1 aberrant value at the 25.0-mg/kg level for week 1.
Mass Selection for Body Weight in Quail

Abstract THE Japanese Quail (Coturnix coturnix japonica) has a relatively brief history as a laboratory animal. A program was begun in 1957 at the Department of Poultry Husbandry, Davis, with the objective of investigating the usefulness of this species in genetic and physiological research (Wilson et al., 1961). While the Japanese quail appears far advanced in its domestication, when this research was initiated we could not find published reports on its use in selection experiments. It was felt worthwhile, therefore, to investigate how body size of quail would respond to artificial selection. Results of two selection experiments for growth rate in quail have recently been reported (Marks and Lepore, 1968; Godfrey, 1968). PROCEDURES Population structure. The base population (line 903) originated in 1959 from crossing 3 populations of Japanese quail initially purchased from California game bird breeders. All were claimed to be recent importations from Japan. Line 903 served as an…
Diffusion Characteristics of Vacancies in Aluminum Interconnects

Computer simulations were performed to investigate the migration energy of vacancies in Al in the presence of grain boundary, dislocation and various imposed forces (such as stress gradients and electro-migration). The energy values were significantly smaller when the vacancy moved into the grain boundary or a dislocation core than in opposite direction. This makes these defects sinks for vacancies from which they are unlikely to migrate out. The major time required for the movement of vacancies is thus limited to within a single grain. Calculations of migration time from the center of the grain to the grain boundary gives time needed for void formation. Calculations of this time assuming an electrical potential gradient along the metal line gave estimates consistent with experimental observations. The increased values of migration energy under compressive stresses suggest that void formation could be deterred by applying such stresses.
A new inotropic aminosteroid: LND 623.

It is usually postulated that the side chain attached to 17β position on the steroid nucleus of the cardioactive glycosides is a major determinant of their pharmacological activity. A new aminosteroid (LND 623) has been prepared. Despite the fact that the structural features quoted above are lacking, the product demonstrates a strong inotropic effect. LND 623 was active at the same range of concentrations as ouabain or digoxin. However, the maximum increase of the contractile force was significantly higher. The strength of the inotropic action is not modified in the presence of propranolol. The preliminary results suggest that the molecular requirements for the interaction of the drugs with the ‘inotropic receptor’ may be re-examined.
Sep15, a Thioredoxin-like Selenoprotein, Is Involved in the Unfolded Protein Response and Differentially Regulated by Adaptive and Acute ER Stresses

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) results in activation of signaling pathways collectively known as the unfolded protein response (UPR). The UPR promotes adaptation of cells to ER stress by transient inhibition of protein translation and transcriptional up-regulation of genes encoding chaperones, oxidoreductases, and ER-associated degradation components. However, it may also trigger apoptosis in response to persistent ER stress. Recently, a novel selenocysteine-containing oxidoreductase, Sep15, has been reported to reside in the ER lumen. It has been proposed that this oxidoreductase may assist oxidative folding and structural maturation of N-glycosylated proteins targeted by UDP-glucose:glycoprotein glucosyltransferase, a chaperone implicated in quality control in the ER that forms a 1:1 complex with Sep15. To address the role of Sep15 in protein folding, we analyzed changes in Sep15 expression in murine fibroblast NIH3T3 cells in response to tunicamycin, brefeldin ...
Reliability and Validity of Self-Report Measures to Evaluate Drug and Violence Prevention Programs.

ABSTRACT The purpose of this paper is to outline the evaluation plan for the Minnesota D.A.R.E. Plus Project, a drug and violence prevention program for young adolescents, and to present the results of psychometric analyses on the measures that will be used in the assessment of the intervention program. The survey instrument was tested using different samples for each stage of its development. The main scale development sample included seventh grade students in urban, suburban and rural schools. The results indicate that the scales constructed are reliable and valid measures of young adolescents' drug use and violent behaviors, as well as intrapersonal, social, and environmental factors related to those behaviors.
Inhibition of DNA synthesis by cross-linking the template to platinum-thiol derivatives of complementary oligodeoxynucleotides

Abstract Unsubstituted oligodeoxynucleotides, or oligodeoxynucleotides linked to poly-(L)-lysine, when hybridized to a 322 base long template, did not inhibit the production of full length DNA copies by the Klenow fragment of E. coli DNA polymerase I. However, synthesis was inhibited if the cysteamine derivative of the same oligomer was cross-linked to the template via PtII. Truncated products were formed by termination of DNA synthesis a small number of bases upstream from the 5'-end of the cross-linked oligomer. AMV reverse transcriptase behaved similarly but was also slightly inhibited by the hybridized oligomer or its poly-lysine derivative.
STABILIZING ROLE OF THE BASEMENT MEMBRANE AND DERMAL FIBERS DURING NEWT LIMB REGENERATION

BACKGROUND Following amputation of a newt limb, tissues at the amputation site undergo histolysis to give rise to a growth bud, or blastema, but they also provide a base on which the regenerate is constructed. Studies suggest that dermal tissues may differentially resist histolysis. METHODS AND RESULTS To examine stability of tissues at the amputation site, more than 80 preblastemal staged regenerating limbs were examined histologically. Initially, all soft tissues not attached to bone retracted and were covered by migrating epithelium. The dermis was seen to be stable during the first week postamputation. Muscle dedifferentiated and was heavily stained with anti-tenascin antibodies, but the intact overlying dermis was unstained. Fiber bundles, revealed by staining with phosphotungstic acid hematoxylin, isolated the dermis from dedifferentiating deeper tissues during the first week postamputation, but partially broke down during the second week. However, the basement membrane (BM) remained as the distalmost intact structure at the amputation site in all limbs examined. The BM was the foundation for new BM synthesis which preceded dermis synthesis in the base of the blastema during the second week, even while undifferentiated cells were accumulating centrally. CONCLUSIONS We suggest that the dermis resists histolysis long enough for new BM to form in continuity with that of the stump. Dermis formation (dermogenesis) distal to the amputation plane begins early as in mammalian healing but is not completed until after blastema formation. Thus, factors that inhibit dermal closure appear to distinguish regenerating from non-regenerating appendages.
Structural Characterization of the Phosphotyrosine Binding Region of a High-Affinity SH2 Domain−Phosphopeptide Complex by Molecular Dynamics Simulation and Chemical Shift Calculations

Three molecular dynamics simulations of the free, phosphate ion-bound and phosphopeptide-bound C-terminal SH2 domain of phospholipase C−γ1 (PLCC·pY) have been performed to aid in the interpretation of chemical shift data and the elucidation of interatomic interactions at the phosphotyrosine (pTyr) binding region. The simulation of the phosphopeptide complex was carried out with newly developed CHARMM force-field parameters for pTyr, optimized against experimental data and ab initio calculations. The lack of NOEs involving phosphate in the binding pocket had necessitated a chemical shift analysis of the pTyr binding region for a more detailed characterization of the hydrogen bonding interactions involving pTyr. Although most of these interactions are not present in the NMR structure used as the simulation starting point, the system converges early in the simulation to a structure more compatible with the chemical shift data. This is supported by ab initio determination of the 1Hη and 1He chemical shifts of...
Energy positive domestic wastewater treatment: the roles of anaerobic and phototrophic technologies.

The negative energy balance of wastewater treatment could be reversed if anaerobic technologies were implemented for organic carbon oxidation and phototrophic technologies were utilized for nutrient recovery. To characterize the potential for energy positive wastewater treatment by anaerobic and phototrophic biotechnologies we performed a comprehensive literature review and analysis, focusing on energy production (as kJ per capita per day and as kJ m−3 of wastewater treated), energy consumption, and treatment efficacy. Anaerobic technologies included in this review were the anaerobic baffled reactor (ABR), anaerobic membrane bioreactor (AnMBR), anaerobic fluidized bed reactor (AFB), upflow anaerobic sludge blanket (UASB), anaerobic sequencing batch reactor (ASBR), microbial electrolysis cell (MEC), and microbial fuel cell (MFC). Phototrophic technologies included were the high rate algal pond (HRAP), photobioreactor (PBR), stirred tank reactor, waste stabilization pond (WSP), and algal turf scrubber (ATS). Average energy recovery efficiencies for anaerobic technologies ranged from 1.6% (MFC) to 47.5% (ABR). When including typical percent chemical oxygen demand (COD) removals by each technology, this range would equate to roughly 40–1200 kJ per capita per day or 110–3300 kJ m−3 of treated wastewater. The average bioenergy feedstock production by phototrophic technologies ranged from 1200–4700 kJ per capita per day or 3400–13 000 kJ m−3 (exceeding anaerobic technologies and, at times, the energetic content of the influent organic carbon), with usable energy production dependent upon downstream conversion to fuels. Energy consumption analysis showed that energy positive anaerobic wastewater treatment by emerging technologies would require significant reductions of parasitic losses from mechanical mixing and gas sparging. Technology targets and critical barriers for energy-producing technologies are identified, and the role of integrated anaerobic and phototrophic bioprocesses in energy positive wastewater management is discussed.
Probing the early development of visual working memory capacity with functional near-infrared spectroscopy

Visual working memory (VWM) is a core cognitive system with a highly limited capacity. The present study is the first to examine VWM capacity limits in early development using functional neuroimaging. We recorded optical neuroimaging data while 3- and 4-year-olds completed a change detection task where they detected changes in the shapes of objects after a brief delay. Near-infrared sources and detectors were placed over the following 10-20 positions: F3 and F5 in left frontal cortex, F4 and F6 in right frontal cortex, P3 and P5 in left parietal cortex, and P4 and P6 in right parietal cortex. The first question was whether we would see robust task-specific activation of the frontal-parietal network identified in the adult fMRI literature. This was indeed the case: three left frontal channels and 11 of 12 parietal channels showed a statistically robust difference between the concentration of oxygenated and deoxygenated hemoglobin following the presentation of the sample array. Moreover, four channels in the left hemisphere near P3, P5, and F5 showed a robust increase as the working memory load increased from 1 to 3 items. Notably, the hemodynamic response did not asymptote at 1-2 items as expected from previous fMRI studies with adults. Finally, 4-year-olds showed a more robust parietal response relative to 3-year-olds, and an increasing sensitivity to the memory load manipulation. These results demonstrate that fNIRS is an effective tool to study the neural processes that underlie the early development of VWM capacity.
Forecasting Plug-In Electric Vehicle Sales and the Diurnal Recharging Load Curve

The expected market penetration of plug-in electric vehicles has drawn much attention to the potential impact on power systems, which to a large extent depends on the number of electric vehicles on the road and the fleet's diurnal recharging load curve. We present two interactive models to jointly forecast plug-in electric vehicle sales and the diurnal recharging load curve in the U.S. between 2012 and 2020. The sales forecasting model is based on information about consumer preferences between hybrid electric vehicles and internal combustion engine vehicles, which can be extracted from historical data. The recharging load forecasting model is based on the assumption that electric vehicle users' recharging behavior will demonstrate a gradual transition from a convenience driven mode in 2012 to a cost driven mode in 2020. A case study is conducted for the Midwest ISO region. Compared to the sales forecasts from the literature, our results turn out to be less optimistic. Our recharging load forecast results also suggest that, if appropriately managed, the impact of plug-in electric vehicles on electricity load would not be overwhelming in the next decade.
DNA bending in solution: NMR studies on the structural roles of A/T tracts and the sequences at the junction

A summary of 1D/2D-NMR studies on d(GA4T4C)2, d(GA4U4C)2, and d(GT4A4C)2 in solution is reported in this article. Results of these studies indicate one important structural property of A - T pairs, i.e., A - T pairs are propeller twisted, which results in a series of interstrand bifurcated H-bonds inside the A/T tract. The structural similarity of d(GA4T4C)2 and d(GA4U4C)2 suggests that the methyl group of thymine may be of little consequence as far as this structural peculiarity of the A/T tract is concerned. Comparison of d(GA4T4C)2 (i.e., “junction B-DNA model”) and d(GT4A4C)2 (i.e., “straight B-DNA model”) structures shows that not only the structural peculiarity of the A/T tract but also the sequence that joins two neighboring A/T tracts play crucial roles in DNA bending. In other words, when two A/T tracts are joined at the A T sequence, a junction is created, whereas when two A/T tracts are connected at the T A sequence, no discontinuity is observed.
Impact of preemptive warfarin dose reduction on anticoagulation after initiation of trimethoprim-sulfamethoxazole or levofloxacin.

Background Antibiotics can potentiate warfarin anticoagulation. While preemptive warfarin dose reduction (DR) upon initiation of antibiotics has been advocated by experts, there are no published data regarding the efficacy of this strategy vs. the conventional strategy of not changing warfarin dose and carefully following international normalized ratio (INR) results. Methods and Results We compared the efficacy of preemptive 10–20% DR vs. no change in warfarin dosing in 40 chronically anticoagulated patients initiating trimethoprim-sulfamethoxazole (TMP-SMX) or levofloxacin. Eighteen patients received preemptive warfarin DR and 22 control patients underwent no change in warfarin dosing. There was no difference between the DR and control groups in the mean INR before beginning antibiotic therapy (2.53 ± 0.12 vs. 2.52 ± 0.11; P > 0.9). Mean interval between initiation of antibiotic and next INR was 5.1 ± 0.4 vs. 4.7 ± 0.5 days for DR vs. control patients, respectively (P > 0.5). For both TMP-SMX and levofloxacin, patients managed with a preemptive warfarin DR strategy did not exhibit a statistically significant change in the INR after initiating antibiotic therapy. In contrast, for each antibiotic, control group patients exhibited a significant increase in mean post-antibiotic INR compared to mean pre-antibiotic INR, though the effect was more pronounced in patients treated with TMP-SMX than with levofloxacin. Of DR group patients who were treated with TMP-SMX, none (0/8) developed a subtherapeutic INR, while 40% (4/10) of levofloxacin-treated patients developed a sub-therapeutic INR. Supra-therapeutic INR results led to transient interruption of warfarin dosing in 2 patients (11%) in the DR group vs. 12 patients (55%) in the control group (P = 0.007). Conclusions Prophylactic warfarin DR of 10–20% is effective in maintaining therapeutic anticoagulation in patients initiating TMP-SMX. An expectant strategy consisting of no change in warfarin dosing with short-term INR follow-up appears reasonable in patients treated with levofloxacin.
Systemic lupus erythematosus, renal disease, hemodialysis and vitamin A

Recent studies indicate that clinically-active systemic lupus erythematosus (SLE) is uncommon in patients with end-stage renal disease undergoing long-term hemodialysis. Several lines of indirect evidence suggest that the dialysis procedure itself may be responsible for inducing remission; that SLE could reflect a toxicity reaction to excessive tissue levels of vitamin A; and that remission associated with dialysis may be due to a gradual reduction in vitamin A levels at the sites of SLE activity.
Determining the utility of recalled lower urinary tract symptoms.

Objectives To assess the utility of recalled American Urological Association Symptom Index (AUA-SI) scores 6 months after an initial outpatient clinic visit. The AUA-SI is a validated questionnaire used to assess a patient's lower urinary tract symptoms (LUTS) over a 4-week period. However, patient recall of their LUTS at greater time points is currently unknown. Methods Between May 2007 and August 2008, 98 patients completed the AUA-SI questionnaire at their initial visit (“Past”). At 6-month follow-up, patients recalled their AUA-SI and quality of life (QoL) scores (“Recall”). As a reference, patients also reported their current symptom scores (“Present”). Descriptive statistics, correlations, regression models, and kappa statistics were performed to assess the associations between the “Past” and “Recall” symptom scores as either categorical (mild, moderate, severe) or continuous (0-35 points) variables. Similar analyses were performed for QoL scores. Results Analyses indicated significant correlations between the “Recall” and “Past” AUA-SI and QoL scores. Although 70% of patients remained in the same categorical groupings, 62% of patients had clinically significant differences (≥ 3 points) between “Recall” and “Past” scores. Approximately, 80% of patients recalled their QoL score accurately (≤ 1 point). Conclusions In an outpatient setting, only approximately one-third of patients can accurately recall AUA-SI scores as a continuous variable from 6 months prior. However, when used as a categorical variable, “Recall” scores may provide some insight into a patient's “Past” urinary symptoms. Future validation in other populations is required.
Paclitaxel plus gallium nitrate and filgrastim in patients with refractory malignancies: a phase I trial.

To determine the maximally tolerated dose of paclitaxel with and without filgrastim (G-CSF) when administered as a 24-hour intravenous infusion after a 120-hour infusion of gallium nitrate at a fixed dose of 300 mg/m 2 /24 hours, 40 patients were entered onto a trial lasting from September 1994 to September 1996. Eligibility included a diagnosis of an advanced malignancy not amenable to curative therapy and up to one previous chemotherapy regimen for metastatic disease. Gallium was administered at a fixed dose of 300 mg/m 2 /day as a continuous intravenous infusion for 120 hours. Paclitaxel starting at 90 mg/m 2 was given concurrently with the last 24 hours of the gallium as a 24-hour intravenous infusion. Cycles were repeated every 21 days. Once the maximum tolerated dose (MTD) of paclitaxel was reached, G-CSF (5 μg/kg/day days 7-16) was added and paclitaxel dose escalation continued. The MTD for paclitaxel without G-CSF was 110 mg/m 2 and 225 mg/m 2 with G-CSF, with neutropenia being the dose-limiting toxicity. A partial response was noted in a patient who had thymoma and a complete response was achieved in a patient who had colon cancer. The recommended phase II dosage is gallium nitrate at 300 mg/m 2 /day over 120 hours, with paclitaxel at 110 mg/ m 2 over 24 hours without G-CSF or 225 mg/m 2 over 24 hours with G-CSF and 0.5 mg calcitriol on days I through 7. Further trials of this modified regimen for outpatient administration are in progress.
Rb-Sr dating of Paleozoic glauconite from the Llano region, central Texas

Abstract Glauconite from eight stratigraphic horizons (Cambrian to Pennsylvanian) in the Llano Uplift, central Texas and two Cretaceous glauconites were analyzed by the Rb-Sr method. Only two untreated samples provide ages in agreement with those anticipated from current best estimates of the geologic time scale. With one exception all the other apparent ages fall short of the estimated age of deposition by as much as 22%. Low ages, the pattern customarily observed, are attributed to postdepositional loss of radiogenic 87 Sr from expandable layers by weathering or during diagenesis. Detailed leaching experiments using a variety of reagents were performed to characterize the behavior of glauconite. The most promising treatment, which we recommend as standard procedure in all future studies, is with ammonium acetate which is able to purge the mineral of loosely-bound Rb and Sr while leaving tightly-bound components intact. After appropriate leach, three other Rb-Sr ages were brought into coincidence with their estimated ages of deposition. In contrast an Upper Cambrian glauconite was found to be extremely resistant to further alteration by chemical attack′, providing an age of 429 ± 17 M yr. Although 17% short of the age of deposition, this age is interpreted as the time of a real event: diagenetic recrystallization induced by burial. Comparison of data from four samples indicates that for Paleozoic glauconite, conditions exist in which the Rb-Sr system is less susceptible to mild disturbance than is the K-Ar system.
Selecting Computer Resources for Inclusion within a Pricing System.

A great deal of interest has been shown in the use of prices as a means of allocating computer resources. However, little effort has been exerted toward determining which resources should be priced. As a step in this direction, a study was undertaken to uncover which resources can be validated for inclusion within a pricing structure. The resources thus found most suitable for pricing are core space and CPU time. A basis for including additional resources within the pricing structure is also provided.
A Framework to Measure the Value of Public Health Services

Public health practitioners understand that there is inherent value in maintaining governmental public health services (GPHS) to protect the population against the spread of disease. But the reality of continuing budgetary constraints facing GPHS suggests that neither politicians nor the public shares a similar perception. To change public attitudes, GPHS must demonstrate and communicate measurable contributions to the population's health and allocate resources to those activities likely to achieve maximum value. At the margin, choices need to be made regarding which services to preserve, which can be cut while minimizing harm to population health outcomes, and which need additional resources. This is especially true at a time when public health systems are expected to incorporate multiple mandates (both funded and unfunded), such as emergency preparedness. In this article, we propose a framework that public health practitioners might use to measure the value of the various services local health departments (LHDs) offer. To develop the framework, we synthesize the results of case study interviews and the characteristics of five current strategies for measuring value that our respondents identify. After describing the study methods and the strategies, we set forth our proposed framework, its rationale, and limitations. We conclude with a discussion of the practice and policy implications.
Similar growth pattern of mouse mammary epithelium cultivated in collagen matrix in vivo and in vitro

Mouse mammary ductal cells cultured in type I collagen gels give rise to three-dimensional multicellular outgrowths consisting of thin spikes which are often branched, and which may have pointed or blunt ends. The significance of these spikes to normal ductal morphogenesis has been unclear, since identical structures are not known to occur in vivo; conversely, it has not been possible to maintain in gel culture the highly structured end buds which are characteristic of ductal elongation in the animal. In order to evaluate whether the pattern of radiating spikes observed in collagen gel cultures results from chemical or physical peculiarities of the culture environment, a small volume of unpolymerized type I collagen solution was injected into mammary gland-free fat pads of young adult mice. After the bubble of collagen had polymerized, an implant of mammary ductal epithelium was introduced into the center of the gel. Histological examination of the implants after 3 to 6 days of growth revealed numerous small epithelial spikes, similar to those observed in gel culture, extending into the fibrous matrix. The early stages of regeneration of mammary implants placed in gland-free fat pads were then examined without the addition of exogenous collagen. In cases where the epithelium happened to contact a fibrous region of the fatty stroma, spikes were also seen to form in these natural collagenous substrates. Whether or not exogenous collagen was used, normal end buds were formed only when epithelial spikes contacted adipocytes. It was concluded that the three-dimensional pattern of radiating tubules in collagen gels in vitro is not merely an artifact of culture, but has a counterpart in vivo whereever regenerating mammary epithelium is surrounded by fibrous stroma. A model is presented in which the pattern of epithelial outgrowth is determined by the physical characteristics of the surrounding stroma; in collagen matrix a comparatively primitive and unspecialized type of morphogenesis occurs which may not require the participation of stromal cells. In contrast, epithelial-adipocyte interactions appear to be necessary for the formation of end buds and subsequent morphogenesis of fully structured mammary ducts.
Effect of filler metal composition on the strength of yttria stabilized zirconia joints brazed with Pd-Ag-CuOx

Various compositions in the Ag-CuOx system are being investigated as potential filler metals for use in air brazing high-temperature electrochemical devices such as solid oxide fuel cells and gas concentrators. Prior work has shown that the melting temperature, and therefore the potential operational temperature, of these materials can be increased by alloying with palladium. The current study examines the effects of palladium addition on the joint strength of specimens prepared from yttria stabilized zirconia (YSZ) bars brazed with three different families of filler metals: Ag-CuO, 5Pd-Ag-CuO, and 15Pd-Ag-CuO. In general, it was found that palladium leads to a small-to-moderate decrease in joint strength, particularly in low copper oxide containing filler metals. However, the declination in strength is likely an acceptable trade-off for increased use temperature. In addition, a critical composition was observed for each filler metal series at which the mechanism for joint failure underwent a transition, typically from ductile to brittle failure. In each case, this composition corresponds approximately to the silver-rich boundary composition of the liquid miscibility gap in each system at the temperature of brazing.
In vivo anticancer synergy mechanism of doxorubicin and verapamil combination treatment is impaired in BALB/c mice with metastatic breast cancer

The development of resistance to anticancer drugs is a major unsolved problem in the chemotherapy treatment of metastatic breast cancer. We have shown that increased expression of P-glycoprotein (P-gp) prevented nuclear entry of the doxorubicin molecules into murine breast cancer cells (4T1-R) leading to doxorubicin chemoresistance. This study was performed to test whether inhibition of P-gp using verapamil could overcome doxorubicin chemoresistance and eliminate multiorgan metastasis 4T1-R cells in BALB/c mouse. The 4T1-R cells were treated with doxorubicin alone, verapamil alone, and a combination of both. Multiorgan metastasis of 4T1-R cells in the presence and in the absence of combination treatment was determined in the BALB/c mouse model. Verapamil induced nuclear translocation of doxorubicin, G2-phase growth arrest and synergistically induced 100% cytotoxicity in 4T1-R cells in culture. However, the combination treatment using verapamil and doxorubicin did not improve the overall survival of BALB/c mice with metastatic breast cancer. Our results indicate that the combination treatment of verapamil and doxorubicin did not inhibit tumor growth in the lungs and liver indicating that the anticancer synergy mechanism of verapamil and doxorubicin is impaired in vivo in BALB/c mouse model with metastatic breast cancer. We propose that understanding the mechanisms as to why the combination of doxorubicin and verapamil treatment was impaired in the mouse model should allow novel approaches to improve chemotherapy response of metastatic breast cancer.
Major groove accessibility of RNA

Chemical acylation experiments showed that the RNA major groove, often assumed to be too deep and narrow to permit recognition interactions, is accessible at duplex termini. Reactivity extended further into the helix in the 5' than in the 3' direction. Asymmetric and large loops between helices uncoupled them, which yielded both enhanced reactivity at terminal base pairs and weaker stabilization enthalpy compared to that in small loops or symmetric loops of the same size. Uncoupled helices have effective helix ends with accessible major grooves; such motifs are attractive contributors to protein recognition, tertiary folding, and catalysis.
Common shocks and relative compensation

This paper studies qualitative properties of an optimal contract in a multi- agent setting in which agents are subject to a common shock. We derive a necessary and sufficient condition for the optimal reward of an agent producing an output level y to be a decreasing (increasing) function of the outputs of the other agents, under the assumption that the agents' outputs are informative signals of the value of the common shock. The condition is that the likelihood ratio p(y, e ,η )/p(y, e � ,η ), where e is a higher effort level than eand η is the value of the common shock, be a decreasing (increasing) function of η. We give examples of applications of the result and examine its consequences for CEO compensation.
Task Complexity and Contingent Information Processing in the Case of Couple's Decision Making

This study provides evidence that the husband-wife decision making process, just as the individual decision making process, is contingent upon the task complexity. As the task became more complex, couples used a multistage strategy more often, a smaller proportion of available information, a smaller proportion of available attributes, and a shorter time per unit of available information. In addition, this study explores differences in the information processing behavior between individuals and couples at equivalent levels of task complexity.
Compact Modeling of Nonlinear Analog Circuits Using System Identification via Semidefinite Programming and Incremental Stability Certification

This paper presents a system identification technique for generating stable compact models of typical analog circuit blocks in radio frequency systems. The identification procedure is based on minimizing the model error over a given training data set subject to an incremental stability constraint, which is formulated as a semidefinite optimization problem. Numerical results are presented for several analog circuits, including a distributed power amplifier, as well as a MEM device. It is also shown that our dynamical models can accurately predict important circuit performance metrics, and may thus, be useful for design optimization of analog systems.
Model electrode structures for studies of electrocatalyst degradation

Proton exchange membrane fuel cells are being extensively studied as power sources because of their technological advantages such as high energy efficiency and environmental friendliness. The most effective catalyst in these systems consists of nanoparticles of Pt or Pt-based alloys on carbon supports. Understanding the role of the nanoparticle size and structure on the catalytic activity and degradation is needed to optimize the fuel cell performance and reduce the noble metal loading. One of the more significant causes of fuel cell performance degradation is the cathode catalyst deactivation. There are four mechanisms considered relevant to the loss of electrochemically active surface area of Pt in the fuel cell electrodes that contribute to cathode catalyst degradation including: catalyst particle sintering such as Ostwald ripening, migration and coalescence, carbon corrosion and catalyst dissolution. Most approaches to study this catalyst degradation utilize membrane electrode assemblies (MEAs), which results in a complex system where it is difficult to deconvolute the effects of the metal nanoparticles. Our research addresses catalyst degradation by taking a fundamental approach to study electrocatalyst using model supports. Nanostructured particle arrays are engineered directly onto planar glassy carbon electrodes. These model electrocatalyst structures are applied to electrochemical activity measurements using amore » rotating disk electrode and surface characterization by scanning electron microscopy. Sample transfer between these measurement techniques enables examination of the same catalyst area before and after electrochemical cycling. This is useful to probe relationships between electrochemical activity and catalyst structure such as particle size and spacing. These model systems are applied to accelerated aging studies of activity degradation. We will present our work demonstrating the mechanistic aspects of catalyst degradation using this simplified geometric system. The active surface area loss observed in repeated cyclic voltammetry is explained through characterization and imaging of the same RDE electrode structures throughout the aging process.« less
NWTS Waste Package Design and Materials Testing

The package materials test program has progressed naturally from materials screening activities during the conceptual design phase to detailed testing of selected materials during the preliminary design phase. The screening activities have been largely completed and recently reviewed. The program is currently moving into the detailed testing phase. Consistent with current conceptual designs, emphasis in waste form studies is on borosilicate glass and spent fuel, the corrosion barrier work stresses carbon steel with titanium alloys as a backup material, and backfill studies emphasize bentonite mixed with sand or with the appropriate host rock. The results of the most recent work have been summarized for all three candidate geologies and some of the major conclusions are given.
Specific volume and adiabatic compressibility measurements of native and aggregated recombinant human interleukin‐1 receptor antagonist: Density differences enable pressure‐modulated refolding

High hydrostatic pressures have been used to dissociate non-native protein aggregates and foster refolding to the native conformation. In this study, partial specific volume and adiabatic compressibility measurements were used to examine the volumetric contributions to pressure-modulated refolding. The thermodynamics of pressure-modulated refolding from non-native aggregates of recombinant human interleukin-1 receptor antagonist (IL-1ra) were determined by partial specific volume and adiabatic compressibility measurements. Aggregates of IL-1ra formed at elevated temperatures (55 degrees C) were found to be less dense than native IL-1ra and refolded at 31 degrees C under 1,500 bar pressure with a yield of 57%. Partial specific adiabatic compressibility measurements suggest that the formation of solvent-free cavities within the interior of IL-1ra aggregates cause the apparent increase in specific volume. Dense, pressure-stable aggregates could be formed at 2,000 bar which could not be refolded with additional high pressure treatment, demonstrating that aggregate formation conditions and structure dictate pressure-modulated refolding yields.
Least privilege and privilege deprivation: towards tolerating mobile sink compromises in wireless sensor networks

Mobile sinks are needed in many sensor network applications for efficient data collection, data querying, localized sensor reprogramming, identifying and revoking compromised sensors, and other network maintenance. Employing mobile sinks however raises a new security challenge: if a mobile sink is given too many privileges, it will become very attractive for attack and compromise. Using a compromised mobile sink, an adversary may easily bring down or even take over the sensor network. Thus, security mechanisms that can tolerate mobile sink compromises are essential. In this paper, based on the principle of least privilege, we first propose several efficient schemes to restrict the privilege of a mobile sink without impeding its capability of carrying out any authorized operations for an assigned task. To further reduce the possible damages caused by a compromised mobile sink, we then propose efficient message forwarding schemes for depriving the privilege assigned to a compromised mobile sink immediately after its compromise has been detected. Through detailed analysis and simulations, we show that our schemes are secure and efficient, and are highly practical for sensor networks consisting of the current generation of sensors.
Microfabricating high-aspect-ratio structures in polyurethane-methacrylate (PUMA) disposable microfluidic devices

We recently reported a new UV-curable polyurethane-methacrylate (PUMA) resin that has excellent qualities as a disposable microfluidic substrate for clinical diagnostic applications. This article discusses strategies to improve the production yield of PUMA chips that contain dense and high-aspect-ratio features, which presents unique challenges in demolding and bonding steps. These fabrication improvements were deployed to produce a microfiltration device that contained closely spaced and high-aspect-ratio columns, suitable for retaining and concentrating cells or beads from a highly diluted suspension.
Ethical issues concerning genetic testing and screening in public health

Genetic testing (predictive analysis that determines genetic alterations in individuals for clinical purposes) and screening (programs that identify persons within a subpopulation who may be at a higher risk for a genetic disease or condition) are increasingly utilized to promote and improve the public's health. The proliferate use of genetic testing and screening may improve public health outcomes, but it also implicates significant ethical, legal, and social concerns. Within the context of conflicting ethical values from the individual and public health perspectives, individual values such as informed consent and privacy and discrimination protections must be respected. Legal and ethical attempts to exceptionalize genetic tests and information (as compared to other health information) to protect privacy and prevent discrimination are well intended, but can also be unjust and impractical. Respect for individual ethical rights has limits. Principles of public health ethics justify voluntary genetic testing and screening and sharing of data for population-based health purposes. Thus, individual rights should not always trump the use of genetic tests or screening programs (or information derived therefrom) for legitimate public health purposes.
Some steps toward the automation of the design of composite dielectric structures

Based on the physical mechanisms believed to underlie the ac electrical breakdown of liquid/solid structures, a volume theory of failure is used to justify the application of a semi-empirical cumulative stress criteria for the assessment of dielectric integrity. The method advocated is extended through the use of a complex Laplace equation to permit the analysis of structures having simultaneous capacitive and resistive stress distributions. Computer algorithms are described for automating dielectric design on this basis and case studies provided to illustrate the utility of the techniques advanced. >
Worrying about What Others Think: A Social-Comparison Concern Intervention in Small Learning Groups.

Small-group learning has become commonplace in education at all levels. While it has been shown to have many benefits, previous research has demonstrated that it may not always work to the advantage of every student. One potential problem is that less-prepared students may feel anxious about participating, for fear of looking “dumb” in front of their peers. This study examines the impact of an intervention to reduce that sort of anxiety—termed social-comparison concern—in small learning groups at the university level. Over the course of an academic quarter (10 weeks), 144 students in 33 small learning groups participated in the study. Approximately one-third received an intervention designed to reduce social-comparison concern by modifying theories of intelligence and attributions for failure. One-third received a study-skills intervention, and the remaining third received no extra resources. The findings suggest that the intervention was successful and that instructors may want to infuse small-group work...
A real time system for robust 3D voxel reconstruction of human motions

We present a multi-PC/camera system that can perform 3D reconstruction and ellipsoid fitting of moving humans in real time. The system consists of five cameras. Each camera is connected to a PC which locally extracts the silhouettes of the moving person in the image captured by the camera. The five silhouette images are then sent, via local network, to a host computer to perform 3D voxel-based reconstruction by an algorithm called SPOT. Ellipsoids are then used to fit the reconstructed data. By using a simple and user-friendly interface, the user can display and observe, in real time and from any view-point, the 3D models of the moving human body. With a rate of higher than 15 frames per second, the system is able to capture non-intrusively, a sequence of human motions.
Amperometric microbial biosensor for p-nitrophenol using Moraxella sp.-modified carbon paste electrode.

An amperometric microbial biosensor for highly specific, sensitive and rapid quantitative determination of p-nitrophenol was developed. The biosensor takes advantage of the ability of Moraxella sp. to specifically degrade p-nitrophenol to hydroquinone, a more electroactive compound than p-nitrophenol. The electrochemical oxidation current of hydroquinone formed in biodegradation of p-nitrophenol was measured at Moraxella sp.-modified carbon paste electrode and correlated to p-phenol concentrations. The optimum response was realized by electrode constructed using 15 mg of dry cell weight per 1 g of carbon paste and operating at 0.3 V (versus Ag/AgCl reference) in pH 7.5, 20 mM sodium phosphate buffer. Operating at these optimum conditions the biosensor had excellent selectivity against phenol derivatives and was able to measure as low as 20 nM (2.78 ppb) p-nitrophenol with very good accuracy and reproducibility. The biosensor was stable for approximately 3 weeks when stored at 4 °C. The applicability of the biosensor to measure p-nitrophenol in lake water was demonstrated.
The ship power electronic revolution: Issues and answers

Power electronics can enable dramatic improvements in marine platforms and ships - increased power, greater automation, with enhanced capabilities and missions. Systems with many power electronic components are emerging, driven by the need for power quality, availability, security, and efficiency. Mechanical ship propulsion systems are being replaced by electric propulsion. Variable speed motor drives are replacing across-the-line motor starters to save energy and decrease load induced instabilities. Uninterruptible power supplies are used everywhere to maintain power continuity and quality. Offshore and deep ocean platforms use many electrical motors for sea keeping and maneuvering. Marine based renewable energy concepts such as tidal and wave power generation and offshore wind farms are emerging. In all the complexity and detail of these is increasing dramatically. Todaypsilas rule-based design processes is no longer adequate. New power electronic system architectures and design concepts are the key to these advances. This paper analyzes these issues and offers solutions in the form of new ideas such as Medium Voltage DC distribution, MVDC, and a ldquorelationalrdquo design process, enabled by physics-based modeling and simulation. Paper also describes the Marine Industries Subcommittee activities in these areas and other related IEEE activities.
Resistance of earth electrodes

By use of potential theory, expressions are obtained for the ohmic resistance of a slender metallic electrode located in a fluid-filled borehole. The configuration is idealised as a spheroidal confocal system.
Adverse outcomes in group psychotherapy: risk factors, prevention, and research directions.

Group forms of therapy have been growing at a rapid rate, in part because of their documented effectiveness and economic considerations such as managed care. It is therefore becoming increasingly important to assess the psychological risks of these interventions. The author provides an overview of the published literature and conference presentations on negative effects in adult outpatient groups. Although much of the literature on adverse outcomes in group therapy focuses on single risk factors (e.g., negative leader, group process, or patient characteristics), the author argues that an interactional model should be encouraged. Means of reducing casualties are also discussed, as well as methodological issues and research directions.