cssi/SciSciGPT-SciSciNet huggingface dataset:
Inhibition of c-Abl tyrosine kinase activity by filamentous actin.

The catalytic activity of c-Abl tyrosine kinase is reduced in fibroblasts that are detached from the extracellular matrix. We report here that a deletion of the extreme C terminus of c-Abl (ΔF-actin c-Abl) can partially restore kinase activity to c-Abl from detached cells. Because the extreme C terminus of c-Abl contains a consensus F-actin binding motif, we investigated the effect of F-actin on c-Abl tyrosine kinase activity. We found that F-actin can inhibit the kinase activity of purified c-Abl protein. Mutations of the extreme C-terminal region of c-Abl disrupted both the binding of c-Abl to F-actin and the inhibition of c-Abl by F-actin. Mutations of the SH3, SH2, and DNA binding domains did not abolish the inhibition of c-Abl kinase by F-actin. Catalytic domain substitutions that affect the regulation of c-Abl by the retinoblastoma protein or the ataxia telangiectasia-mutated kinase also did not abolish the inhibition of c-Abl by F-actin. Interestingly, among these c-Abl mutants, only the ΔF-actin c-Abl retained kinase activity in detached cells. Taken together, the data suggest that F-actin is an inhibitor of the c-Abl tyrosine kinase and that this inhibition contributes in part to the reduced Abl kinase activity in detached cells.
Licensing of natural killer cells by self‐major histocompatibility complex class I

Natural killer (NK) cells have potent capacities to immediately kill cellular targets and produce cytokines that may potentially damage normal self-tissues unless they are kept in check. Such tolerance mechanisms are incompletely understood. Here we discuss recent studies suggesting that NK cells undergo a host major histocompatibility complex (MHC) class I-dependent functional maturation process, termed 'licensing'. Ironically, licensing directly involves inhibitory receptors that recognize target cell MHC class I molecules and block activation of NK cells in effector responses. This process results in two types of tolerant NK cells: functionally competent (licensed) NK cells, whose effector responses are inhibited by self-MHC class I molecules through the same receptors that conferred licensing, and functionally incompetent (unlicensed) NK cells.
Xanthine Oxidase Does Not Mediate the Antiproliferative Effects of Interferon-γ in Human Umbilical Vein Endothelial Cells

ABSTRACT Interferon-γ (IFN-γ) has potent antiproliferative effects on the endothelium, although the specific mechanisms responsible for this effect are not clear. We tested the hypothesis that suppression of endothelial cell proliferation by IFN-γ is mediated by an increase in xanthine oxidase-derived O2. Human umbilical vein endothelial cells (HUVEC) were exposed to recombinant human IFN-γ. We found that [3H]thymidine uptake decreased (p 0.05) on [3H]thymidine uptake of IFN-γ-treated cells. In parallel, IFN-γ decreased (p 0.05) on cell counts of IFN-γ-treated or control HUVEC. In addition, xanthine oxidase activity of HUVEC did not (p > 0.05) increase following treatment with IFN-γ. We conclude that IFN-γ suppresses HUVEC proliferation by a mechanism independent of O2 pro...
Structural phase transformations and the equations of state of calcium chalcogenides at high pressure

The crystal structures of three calcium chalcogenides CaS, CaSe, and CaTe were investigated by energy-dispersive x-ray-diffraction techniques using a synchrotron source to a static compression up to 52 GPa. For CaS and CaSe, a first-order phase transformation from the NaCl phase to the CsCl phase was observed at 40 and 38 GPa, respectively. For CaTe, it first transforms from the NaCl phase to an intermediate state possibly with a mixture of NaCl and MnP phases at 25 GPa, and then to the CsCl phase above 33 GPa. The phase transitions were reversible with small hysteresis. The equations of state and bulk moduli were obtained for all three compounds. The systematic behavior among the calcium chalcogenides under compression and the unusual transition sequence of CaTe are discussed.
Setting the Stage for Clinical Simulation: Developing an Introductory Video

Abstract Although clinical simulations are an integral part of the skills lab curriculum at The Frances Payne Bolton School of Nursing, faculty felt there was a need to add a visual dimension to simulation experiences. Rather than just verbally introduce a simulation by reading a case study, faculty wanted students to feel as though they were present in the clinical setting receiving a report on a patient they could see and hear. In an attempt to capture a glimpse of the clinical setting, faculty, teaching assistants, and undergraduate nursing students filmed a brief video with participants portraying a patient and members of the health care team in an actual hospital setting. The roles, script, and props were carefully chosen to correspond with the objectives of a clinical simulation frequently used in the learning resource center with freshmen nursing students involving comfort care and communication. The use of this introductory video to set the stage for the simulation has heightened students' sense of realism while adding a visual dimension to the simulation experience. Realistic videos which accurately introduce an authentic clinical situation may significantly enhance the simulation experience and facilitate transition of knowledge from the learning resource center environment to the clinical setting.
Late withdrawal of cyclosporine in stable renal transplant recipients

Abstract The use of cyclosporine (CsA) in renal transplantation has been associated with an improvement in 1-year graft survival, but has not changed the rate of late graft loss. We sought to determine whether the intent to withdraw CsA late after renal transplantation affects renal transplant survival and whether there is a racial difference in the effect of CsA withdrawal. This retrospective study included 384 consecutive patients receiving a renal transplant during the 1984 to 1991 period who were treated with CsA/azathioprine/prednisone and who had a functioning allograft 6 months following transplantation. Of these, 97 were electively withdrawn from CsA at a median of 22 months following transplantation. Factors significantly associated with the decision to withdraw CsA included white race, older age, and lower serum creatinine. Acute rejection within 6 months of stopping CsA occurred in 12 patients (12.4%), including nine of 78 (11.5%) white patients and three of 19 (15.8%) black patients. For the group of 287 patients who were not withdrawn from CsA, the 6-year graft survival rate was 59% (95% confidence interval, 52%, 66%). For the group of patients taken off of CsA, the 6-year graft survival rate was 84% (95% confidence interval, 76%, 92%). Cox proportional hazard survival analysis indicated that the intent to discontinue CsA was associated with better graft survival, with a hazard ratio of 0.37 (95% confidence interval, 0.20, 0.70), independent of other variables that may affect graft survival. A separate analysis controlling for waiting time bias also favored the CsA withdrawal group. There was no detectable racial difference in the effect of CsA withdrawal on graft survival. Withdrawal of CsA in selected stable patients at a median of 22 months after transplantation is a reasonable option, but carries a significant risk of acute rejection. Older white patients with good renal function may be the best candidates for CsA withdrawal.
Comparative Toxicology of Tetrachlorobiphenyls in Mink and Rats I. Changes in Hepatic Enzyme Activity and Smooth Endoplasmic Reticulum Volume

Abstract Mink have been shown previously to be extraordinarily sensitive to polychlorinated biphenyls (PCBs) and related classes of halogenated hydrocarbons. This study explored several aspects of the acute response of mink to two purified tetrachlorobiphenyl (TCB) congeners and compared their response with that of the rat, a less sensitive and more thoroughly studied species. Young female pastel mink and young female Sprague-Dawley rats received three daily intraperitoneal injections with equimolar doses of either 2,4,2′,4′-TCB or 3,4,3′,4′-TCB, and were sacrificed after 7 days. Two control groups were used for each species; one was allowed free access to food and the other was pairfed to the 3,4,3′,4′-TCB treatment group. Rats remained clinically normal, while mink treated with 3,4,3′,4′-TCB developed severe anorexia, diarrhea, and melena. Both species had significant increases in hepatic cytochrome P-450 content and the characteristic shift in the spectral maxima from 450 to 448 nm in the 3,4,3′,4′-TCB- but not in the 2,4,2′,4′-TCB-treated animals. Rats but not mink had increased activities of several hepatic monooxygenases in response to both congeners while microsomal epoxide hydrolase was increased in rats after 2,4,2′,4′-TCB and in mink after 3,4,3′,4′-TCB. Significant increases in the relative volume of smooth endoplasmic reticulum within hepatocytes of 2,4,2′,4′-TCB-treated rats but not mink were confirmed by ultrastructural morphometry. Accumulation of both congeners was greater in adipose tissue than in the liver of either species. In both species, concentrations in adipose tissue were much greater for 2,4,2′,4′-TCB than for 3,4,3′,4′-TCB. PCB toxicosis in mink, as in other species, appeared to be dependent on isomeric arrangement of chlorine substituents. However, unlike other species, the toxicosis was not associated with biochemical or morphological evidence of hepatic enzyme induction. Moreover, the target organ of 3,4,3′,4′-TCB toxicosis in mink was the small intestinal mucosa.
Dense Surface Reconstruction With Shadows in MIS

Three-dimensional reconstruction of internal organ surfaces provides useful information for better control and guidance of the operations of surgical tools for minimally invasive surgery (MIS). The current reconstruction techniques using stereo cameras are still challenging due to the difficulties in correspondence matching in MIS, since there is very limited texture but significant specular reflection on organ surfaces. This paper proposes a new approach to overcome the problem by introducing weakly structured light actively casting surgical tool shadows on organ surfaces. The contribution of this paper is twofold: first, we propose a robust approach to extract shadow edges from a sequence of shadowed images; second, we develop a novel field surface interpolation (FSI) approach to obtain an accurate and dense disparity map. Our approach does not rely on texture information and is able to reconstruct accurate 3-D information by exploiting shadows from surgical tools. One advantage is that the point correspondences are directly calculated and no explicit stereo matching is required, which ensures the efficiency of the method. Another advantage is the minimum hardware requirement because only stereo cameras and a separated single-point light source are required. We evaluated the proposed approach using both phantom models and ex vivo images. Based on the experimental results, we achieved the precision of the recovered 3-D surfaces within 0.7 mm for phantom models and 1.2 mm for ex vivo images. The comparison of disparity maps indicates that with the addition of shadows, the proposed method significantly outperforms the state-of-the-art stereo algorithms for MIS.
Assessing Nitrogen-Saturation in a Seasonally Dry Chaparral Watershed: Limitations of Traditional Indicators of N-Saturation

To evaluate nitrogen (N) saturation in xeric environments, we measured hydrologic N losses, soil N pools, and microbial processes, and developed an N-budget for a chaparral catchment (Sierra Nevada, California) exposed to atmospheric N inputs of approximately 8.5 kg N ha−1 y−1. Dual-isotopic techniques were used to trace the sources and processes controlling nitrate (NO3 −) losses. The majority of N inputs occurred as ammonium. At the onset of the wet season (November to April), we observed elevated streamwater NO3 − concentrations (up to 520 µmol l−1), concomitant with the period of highest gaseous N-loss (up to 500 ng N m−2 s−1) and suggesting N-saturation. Stream NO3 − δ15N and δ18O and soil N measurements indicate that nitrification controlled NO3 − losses and that less than 1% of the loss was of atmospheric origin. During the late wet season, stream NO3 − concentrations decreased (to <2 µmol l−1) as did gaseous N emissions, together suggesting conditions no longer indicative of N-saturation. We propose that chaparral catchments are temporarily N-saturated at ≤8.5 kg N ha−1 y−1, but that N-saturation may be difficult to reach in ecosystems that inherently leak N, thereby confounding the application of N-saturation indicators and annual N-budgets. We propose that activation of N sinks during the typically rainy winter growing season should be incorporated into the assessment of ecosystem response to N deposition. Specifically, the N-saturation status of chaparral may be better assessed by how rapidly catchments transition from N-loss to N-retention.
Activated diffusion of methane in coal

Abstract Two techniques have been used to study the diffusion of methane in American coals of rank varying from low volatile matter anthracite to high volatile content bituminous. Diffusion of methane out of coal at sub-atmospheric pressures has been studied using a constant pressure apparatus. Diffusion of methane into coal at elevated pressures has been studied using a constant volume apparatus. Diffusion in the micropore system is activated, the activation energy varying from 3.5 kcal/mol ∗ for low volatile matter anthracite to about 7.0 kcal/mol for bituminous coals. This suggests that the average size of the accessible micropores in the anthracites is larger than that in the bituminous coals.
Phosphorylation or Glutamic Acid Substitution at Protein Kinase C Sites on Cardiac Troponin I Differentially Depress Myofilament Tension and Shortening Velocity

There is evidence that multi-site phosphorylation of cardiac troponin I (cTnI) by protein kinase C is important in both long- and short-term regulation of cardiac function. To determine the specific functional effects of these phosphorylation sites (Ser-43, Ser-45, and Thr-144), we measured tension and sliding speed of thin filaments in reconstituted preparations in which endogenous cTnI was replaced with cTnI phosphorylated by protein kinase C-e or mutated to cTnI-S43E/S45E/T144E, cTnI-S43E/S45E, or cTnI-T144E. We used detergent-skinned mouse cardiac fiber bundles to measure changes in Ca2+-dependence of force. Compared with controls, fibers reconstituted with phosphorylated cTnI, cTnI-S43E/S45E/T144E, or cTnI-S43E/S45E were desensitized to Ca2+, and maximum tension was as much as 27% lower, whereas fibers reconstituted with cTnI-T144E showed no change. In the in vitro motility assay actin filaments regulated by troponin complexes containing phosphorylated cTnI or cTnI-S43E/S45E/T144E showed both a decrease in Ca2+ sensitivity and maximum sliding speed compared with controls, whereas filaments regulated by cTnI-S43E/S45E showed only decreased maximum sliding speed and filaments regulated by cTnI-T144E demonstrated only desensitization to Ca2+. Our results demonstrate novel site specificity of effects of PKC phosphorylation on cTnI function and emphasize the complexity of modulation of the actin-myosin interaction by specific changes in the thin filament.
Two-point boundary value problems by the extended Adomian decomposition method

In this paper, we present an efficient numerical algorithm for solving two-point linear and nonlinear boundary value problems, which is based on the Adomian decomposition method (ADM), namely, the extended ADM (EADM). The proposed method is examined by comparing the results with other methods. Numerical results show that the proposed method is much more efficient and accurate than other methods with less computational work.
Failure of postictal growth hormone rise in a patient with thalamic lesions

A patient with bilateral thalamic lesions had a spontaneous generalized convulsion during nocturnal polygraphic recording. Postictal measurements of cortisol and prolactin showed the expected rise of plasma values at 30 and 60 minutes after the seizure, but growth hormone did not increase. This observation suggests that suprahypothalamic mechanisms regulating growth hormone release differ from those involved in the neural control of cortisol-ACTH and prolactin secretion. The thalamus may intervene as a regulatory center in the release of growth hormone.
A family portrait of the RIO kinases

The RIO family of atypical serine protein kinases has been first characterized only recently. It consists of enzymes that contain a unique domain with a characteristic kinase sequence motif and usually some additional domains. At least two RIO proteins, Rio1 and Rio2, are present in organisms varying from Archaea to humans, with a third Rio3 subfamily present only in multicellular eukaryotes. Yeast Rio1 and Rio2 proteins have been implicated in the processing of 20 S pre-rRNA and are necessary for survival of the cells. Crystal structures of Archaeoglobus fulgidus Rio1 and Rio2 have shown that whereas the overall fold of these enzymes resembles typical protein kinases, some of the structural domains, particularly those involved in peptide substrate binding, are not present. The mode of binding of nucleotides also differs from that found in typical protein kinases. Although it has been shown that both Rio1 and Rio2 have the enzymatic activity of kinases and are capable of autophosphorylation, the biological substrates of RIO proteins and their full biological role still remain to be discovered.
Galactose toxicity in chick cells in vitro.

Abstract 1. 1. Chick cells maintained in a chemically defined medium developed evidence of severe galactose toxicity while control cells maintained in glucose, mannose or fructose remained normal. 2. 2. In contrast, galactose toxicity was not observed in two normal cell lines of primate origin. 3. 3. Oxidation of galactose to CO2 occurred in chick cells, but at a much slower rate than in normal primate cells. 4. 4. Galactose had no effect on glucose utilization in chick cells as measured by Co2 production, but glucose severely inhibited galactose utilization. 5. 5. These observations suggest that galactose toxicity in chick cells is not based on a hyperosmolar state or competition by galactose for glucose transport, but that a biochemical abnormality in galactose metabolism may exist.
Cancer stem/progenitor cell active compound 8-quinolinol in combination with paclitaxel achieves an improved cure of breast cancer in the mouse model.

Increasing evidence suggests that breast cancer is caused by cancer stem cells and the cure of breast cancer requires eradication of breast cancer stem cells. In this study, we established and characterized a sphere culture model derived from side population cells from the human breast cancer cell line MCF7. The sphere culture could be maintained long term and was enriched in cells expressing known breast cancer stem cell marker CD44+CD24−. These sphere cells showed higher colony formation ability in vitro and higher tumorigenicity in vivo than MCF7 cells, suggesting the enrichment of breast cancer stem/progenitor cells. To identify compounds that preferentially inhibit the sphere cells, we performed a compound library screening. Two lead compounds, NSC24076 and NSC125034 and an analog of NSC125034, 8-quinolinol (8Q), were identified as having preferential activity against the sphere cells. 8Q showed some antitumor activity alone but had much better therapeutic effect and relapse prevention when combined with paclitaxel than either 8Q or paclitaxel alone in both MCF7 and MDA-MB-435 xenograft models. We propose that compounds selectively targeting cancer stem/progenitor cells when combined with standard chemotherapy drugs may produce an improved treatment of cancer without significant relapse.
Artificial Effects on Cryogenic Fracture Toughness of the Main Structural Alloy for the Super Light Weight Tank

In 1996, Marshall Space Flight Center developed a multistep heating rate-controlled (MSRC) aging technique that significantly enhanced cryogenic fracture toughness (CFT) and reduced the statistical spread of fracture toughness values in alloy 2195 by controlling the location and size of strengthening precipitate T1. However, it could not be readily applied to flight-related hardware production, primarily because large-scale production furnaces are unable to maintain a heating rate of 0.6 C (1 F)/hr. In August 1996, a new program was initiated to determine whether the MSRC aging treatment could be further modified to facilitate its implementation to flight hardware production. It was successfully redesigned into a simplified two-step aging treatment consisting of 132 C (270 F)/20 hr + 138 C (280 F)/40 hr. Results indicated that two-step aging can achieve the same yield strength levels as those produced by conventional aging while providing greatly improved ductility. Two-step aging proved to be very effective at enhancing CFT, enabling previously rejected materials to meet simulated service requirements. Cryogenic properties are improved by controlling T1 nucleation and growth so that they are promoted in the matrix and suppressed in the subgrain boundaries.
Preoperative parenteral parecoxib and follow-up oral valdecoxib reduce length of stay and improve quality of patient recovery after laparoscopic cholecystectomy surgery.

UNLABELLED In this randomized, double-blinded, placebo-controlled study, we evaluated the effects of preoperative IV parecoxib sodium (parecoxib) followed by postoperative oral valdecoxib on length of stay, resource utilization, opioid-related side effects, and patient recovery after elective laparoscopic cholecystectomy. Patients were randomized to receive a single IV dose of parecoxib 40 mg (n = 134) or placebo (n = 129) 30-45 min before the induction of anesthesia. Six to 12 h after the IV dose, the parecoxib group received a single oral dose of valdecoxib 40 mg, followed by valdecoxib 40 mg once daily on postoperative Days 1-4 and then 40 mg once daily as needed on Days 5-7. Patients in the parecoxib/valdecoxib group had a shorter length of stay in the postanesthesia care unit (78 +/- 47 min) compared with those taking placebo (90 +/- 49 min; P < 0.05). Patients in the parecoxib/valdecoxib group also had reduced pain intensity and, after discharge, experienced a significant reduction in vomiting in the first 24 h, slept better, returned to normal activity earlier, and expressed greater satisfaction than placebo patients (P < 0.05). Preoperative parecoxib followed by postoperative valdecoxib is a valuable adjunct for treating pain and improving patient outcome after laparoscopic cholecystectomy. IMPLICATIONS The administration of preoperative IV parecoxib followed by oral valdecoxib after surgery resulted in a shorter length of stay in the postoperative anesthesia care unit, a better quality of postoperative recovery, and a faster return to normal activity, with greater patient satisfaction, after laparoscopic cholecystectomy.
Intracranial collateralization determines hemodynamic forces for carotid plaque disruption

Introduction Percent diameter reduction provides an imperfect assessment of the risk for stroke from carotid atheroembolism. Stroke associated with atherosclerotic carotid stenosis commonly results from plaque disruption brought about by hemodynamic shear stress and Bernoulli forces. The aim of the present study was to predict the effect of incomplete intracranial collateralization through the circle of Willis (COW) on disruptive hemodynamic forces acting on carotid plaques. Methods A simple circuit model of the major pathways and collaterals that form and supply the COW was developed. We modeled the intra- and extracranial arterial circuits from standard anatomic references, and the pressure-flow relationships within these conduits from standard fluid mechanics. The pressure drop caused by (laminar and turbulent) flow along the internal carotid artery path was then computed. Carotid circulation to the brain was classified as being with or without collateral connections through the COW, and the extracranial carotid circuit as being with or without severe stenosis. The pressure drop was computed for each scenario. Finally, a linear circuit model was used to compute brain blood flow in the presence/absence of a disconnected COW. Results Pressure drop across a carotid artery stenosis increased as the flow rate within the carotid conduit increased. Poststenotic turbulence from a sudden expansion distal to the stenosis resulted in an additional pressure drop. Despite the stenosis, mean brain blood flow was sustained at 4.15 mL/s bilaterally. In the presence of an intact (collateralized) COW, this was achieved by enhanced flow in the contralateral (normal) carotid artery. However, in a disconnected COW, this was achieved by sustained systolic and enhanced diastolic flow through the stenosed artery. For a similar degree of stenosis, flow and velocity across the plaque was much higher when the COW was disconnected compared with an intact COW. Furthermore, the pressure drop across a similar stenosis was significantly higher with a disconnected COW compared with an intact COW. Conclusions Incomplete intracranial collateralization through the COW results in increased flow rates and velocities, and therefore large pressure drops across a carotid artery stenosis. This exerts large disruptive shear stress on the plaque compared with patients with an intact COW. Percent diameter reduction provides an inaccurate assessment of risk for atheroembolic stroke. An assessment of carotid flow rates, flow velocities, and the intracranial collateral circulation may add independent information to refine the estimation of stroke risk in patients with asymptomatic carotid atherosclerosis.
A new histone found only in mammalian tissues with little cell division

Abstract The several criteria are discussed which support the idea that the new electrophoretic band, found in histones of non-replicating tissue, is indeed a previously unreported histone.
Toward educative communities: teacher education and the quest for the reflective practitioner

The current effort to reform teacher education around the aim of developing reflective teachers is unlikely to make a significant difference unless it is tied to a larger project that challenges the training orientation that dominates our understanding of teaching and schooling. The authors argue that the development of educative communities, based upon an ethic of caring and the establishment of dialogicalrelations, can serve as such an ideal. A discussion of this ideal is followed by two case studies that focus on ways that prcservice programs can link values and meaning to technical concerns, honor and examine what preservice teachers believe and know, and encourage the development of collegial relations.
BAL increases the arsenic-74 content of rabbit brain

The 74As content of the brain of rabbits was doubled following administration of BAL (2,3-dimercapto-1-propanol). DMPS (2,3-dimercapto-1-propanesulfonic acid, sodium salt), however, decreased the rabbit brain arsenic concentration. The use of BAL as the drug of choice for treatment of arsenic intoxication should be viewed with caution and re-examined.
First-principles computation of mantle materials in crystalline and amorphous phases

Abstract First-principles methods based on density functional theory are used extensively in the investigation of the behavior and properties of mantle materials over broad ranges of pressure, temperature, and composition that are relevant. A review of computational results reported during the last couple of decades shows that essentially all properties including structure, phase transition, equation of state, thermodynamics, elasticity, alloying, conductivity, defects, interfaces, diffusivity, viscosity, and melting have been calculated from first principles. Using MgO, the second most abundant oxide of Earth’s mantle, as a primary example and considering many other mantle materials in their crystalline and amorphous phases, we have found that most properties are strongly pressure dependent, sometimes varying non-monotonically and anomalously, with the effects of temperature being systematically suppressed with compression. The overall agreement with the available experimental data is excellent; it is remarkable that the early-calculated results such as shear wave velocities of two key phases, MgO and MgSiO 3 perovskite, were subsequently reproduced by experimentation covering almost the entire mantle pressure regime. As covered in some detail, the defect formation and migration enthalpies of key mantle materials increase with pressure. The predicted trend is that partial MgO Schottky defects are energetically most favorable in Mg-silicates but their formation enthalpies are high. So, the diffusion in the mantle is likely to be in the extrinsic regime. Preliminary results on MgO and forsterite hint that the grain boundaries can accommodate point defects (including impurities) and enhance diffusion rates at all pressures. The structures are highly distorted in the close vicinity of the defects and at the interface with excess space. Recent simulations of MgO–SiO 2 binary and other silicate melts have found that the melt self-diffusion and viscosity vary by several orders of magnitudes with pressure, temperature, and composition. The predicted high compressibility and complex dynamical behavior can be associated with structural changes (involving non-bridging oxygen, oxygen tri-clusters, Si–O pentahedra, etc.) occurring on compression. We envision future prospect for massively parallel/distributed computing of unprecedented magnitude and scope in the study of relevant materials for Earth, super-Earth, and other planets. A renewed computational theme perhaps should be the first-principles simulations of large systems (with long runs) that are necessary to explore realistic (natural) compositions, polycrystalline phases, multi-component melts, crystal/melt interfaces, trace element partitioning, etc.
Abstract 5520: Therapeutic vaccination with epitope-enhanced and wild-type TARP peptides in stage D0 prostate cancer

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Background: T-cell receptor alternate reading frame protein (TARP) is immunogenic, is expressed in ∼95% of prostate cancer specimens and hence is a good candidate for therapeutic vaccination. The immunogenicity of HLA-A*0201 binding TARP peptides can be improved through epitope-enhancement achieved by amino acid substitutions that result in increased HLA binding affinity and immunogenicity at least in mice. We conducted a pilot study to determine the safety and immunogenicity of TARP peptide vaccination and its impact on PSA doubling time (PSADT) in men with Stage D0 prostate cancer. Methods: HLA-A*0201 positive men were randomized to receive epitope-enhanced (29-37-9V) or wild type (27-35) TARP peptides administered as a peptide emulsion with Montanide ISA 51VG plus GM-CSF (Arm A) or as an autologous peptide-pulsed dendritic cell vaccine (Arm B). Vaccines are administered q 3 weeks for a total of 5 vaccines with an optional 6th dose of vaccine at 36 weeks based on immune response or PSADT criteria and a booster dose of vaccine for all patients at 48 weeks. Results: 26 patients have enrolled in the study to date (n = 14 Arm A, n = 12 Arm B) with a mean on study duration of 7.5 months. Mean baseline cohort characteristics: age 63 yrs, PSA 4.43, PSADT 7.3 months and Gleason Score 6.7 with 19 of 26 s/p radical prostatectomy. TARP vaccination was safe and well tolerated with adverse events limited to local injection site reactions < Grade 2. Nine of 18 patients (50%) reaching 24 weeks on study were documented to have an increase in their PSADT compared to baseline. Mean Percent Increase/Prolongation in PSADT: ![Figure][1] Surprisingly TARP-specific IFN-γ ELISPOT responses have been detected ex vivo in only 3 of 14 (21%) patients examined to date. Conclusion: Vaccination with wild type and epitope-enhanced TARP peptides results in prolongation of PSADT in a substantial fraction of patients. The immunologic correlates responsible for PSADT lengthening are poorly understood and require additional study. 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 5520. doi:10.1158/1538-7445.AM2011-5520 [1]: pending:yes
Regional hemodynamic adaptation during the menstrual cycle

Abstract Objective: To determine whether regional differences exist in uterine and systemic hemodynamic responses to the menstrual cycle, whether the hormonal environment correlates with the changes, and whether uterine artery hemodynamic adaptation depends on the side of ovulation. Methods: Twenty nulliparas had transvaginal Doppler ultrasonographic assessment of the uterine and upper-extremity radial arteries at three time points in each of two menstrual cycles. Doppler indices (peak systolic velocity, end-diastolic velocity, time-averaged maximum velocity, resistance index [RI], and blood flow) were measured in the radial and uterine arteries. Women were examined in the menstrual (cycle day 2–3), follicular (cycle day 9–10), and luteal phases (cycle day LH surge plus 9–10). At each time, serum estradiol (E2) and progesterone were measured by radioimmunoassay. Statistical analyses were repeated-measures analysis of variance and the Fisher least significant difference procedure. Results: Thirty-four nonconception ovulatory cycles were evaluated. Blood flow in each uterine artery increased significantly from a mean (± standard deviation) of 22.4 ± 7.3 mL/minute in the follicular phase to 30.7 ± 13.7 mL/minute in the luteal phase, which coincided with a reduction in the RI. The changes were independent of the side of ovulation. The radial artery did not parallel these changes (follicular blood flow of 27.2 ± 13.9 mL/minute; luteal blood flow of 24.7 ± 10.5 mL/minute). We did not identify any significant correlation between these changes and serum E2 or progesterone concentrations. Conclusion: We identified differences in the hemodynamic responses of the uterine artery compared with the radial artery during the menstrual cycle. We believe the difference indicates distinct regional control of vascular response during the menstrual cycle.
Modulation of the Discriminative Stimulus Effects of d-Amphetamine by Mu and Kappa Opioids in Squirrel Monkeys

It has been reported that the discriminative stimulus effects of cocaine in squirrel monkeys can be potentiated by mu opioid agonists and attenuated by kappa opioid agonists. The purpose of this study was to extend these observations by examining the effects of mu and kappa opioids agonists on the discriminative stimulus effects of d-amphetamine (AMPH). Five squirrel monkeys were trained to discriminate 0.3 mg/kg of AMPH (i.m.) from saline using a stimulus termination/avoidance task. AMPH and cocaine substituted dose dependently for the AMPH training stimulus in all five monkeys. The AMPH training dose was completely antagonized by 0.1 mg/kg of the D1 dopamine antagonist SCH 39166. When administered alone, the kappa agonist U69,593 substituted partially or completely for AMPH in four of five monkeys, the kappa agonist enadoline substituted completely for AMPH in two of five monkeys, and morphine substituted completely for AMPH in one monkey. In all five monkeys, pretreatment with some doses of U69,593 or enadoline attenuated the discriminative stimulus effects of AMPH; however, some doses of U69,593 and enadoline also potentiated the effects of AMPH in at least two monkeys. Morphine pretreatment potentiated the discriminative stimulus effects of AMPH in three monkeys and either attenuated or did not alter these effects in two monkeys. Morphine pretreatment did not significantly alter the discriminative stimulus effects of cocaine except in one monkey. These data indicate large individual differences in the abilities of mu and kappa opioid agonists to alter the discriminative stimulus effects of AMPH.
Substitution profiles of N-methyl-d-aspartate antagonists in ethanol-discriminating inbred mice

C57BL/6J (B6) and DBA/2J (D2) inbred mice show pronounced differences in ethanol-induced behaviors, such as loss of righting reflex and locomotor activation, among others. They also differ in measures of conditioned place preference and oral self-administration of ethanol. In the current study, I examined whether B6 and D2 mice differed in their expression of the N-methyl-D-aspartate (NMDA) receptor-mediated component of the discriminative stimulus effects of ethanol. B6 and D2 mice were trained to discriminate ethanol (1.5 g/kg, i.p.) from saline in a two-choice, milk-reinforced operant procedure. After training was completed, substitution and response rate dose-effect curves were generated for ethanol; the uncompetitive NMDA antagonists phencyclidine and ketamine; and the competitive NMDA antagonist D-CPPene. Dose-effect curves were also generated for midazolam, cocaine, m-chlorophenylpiperazine (mCPP), morphine, and gamma-hydroxybutyric acid (GHB). B6 and D2 mice learned the ethanol-versus-saline discrimination. Phencyclidine produced near full substitution for ethanol in both strains, whereas ketamine fully substituted for ethanol only in B6 mice. D-CPPene partially substituted for ethanol in both strains. Moderate doses of phencyclidine produced greater response rate-increasing effects in B6 mice than in D2 mice, and high doses of phencyclidine were more potent for suppressing response rates in D2 mice. In contrast, D-CPPene had similar response rate-increasing effects in both strains, but high doses produced more potent response rate-decreasing effects in B6 mice. Among the other drugs tested, only midazolam produced substantial substitution for ethanol. Taken together, these findings seem to indicate that the behavioral effects of NMDA antagonists differ between strains, but that the NMDA-mediated component of the discriminative stimulus effects of ethanol is similar in B6 and D2 mice.
Empirical Modeling of Direct Electric Current Effect on Machining Cutting Force

Metallic materials can be made more ductile and be formed at lower forces through the application of electrical current during deformation, termed Electrically-Assisted Forming (EAF). The current provides a degree of resistive heating, but also facilitates deformation by direct electrical mechanisms (termed the electroplastic effect). It is envisioned that this approach, currently applied to bulk/sheet deformation, could also be used to reduce the flow stress in the deformation zone of the machining shear plane. The objective of this work is to study and model the effect of electric current on forces in machining in order to relate the force reduction to the current level and machining process parameters. To perform this, skiving tests and orthogonal machining tests are performed with varying electrical conditions. It is shown that application of electric current does reduce machining force by up to 60% under certain conditions.Copyright © 2013 by ASME
Voter Perceptions of the Cost of Government: the Case of Local School Expenditures in Louisiana

Voter perceptions of the burden from the two major indirect taxes (sales tax and nonresidential property tax) and from income generated from wealth held by the public sector are examined. Using two alternative median voter models, data on the finances of local school districts in Louisiana are used to estimate voter perceptions of the burden from each revenue source. The results suggest that Louisiana voters apparently perceive that they bear little of the burden from either the locally imposed sales tax or the school tax levied on property (other than the school tax levied on residential or commercial property). Furthermore, the empirical evidence also indicates that voters do not perceive that school expenditures financed from the income of wealth held by the public sector could have alternatively been used for tax reduction.
Alternate and new brominated flame retardants detected in U.S. house dust.

Due to the voluntary withdrawals and/or bans on the use of two polybrominated diphenyl ether (PBDE) commercial mixtures, an increasing number of alternate flame retardant chemicals are being introduced in commercial applications. To determine if these alternate BFRs are present in indoor environments, we analyzed dust samples collected from 19 homes in the greater Boston, MA area during 2006. Using pure and commercial standards we quantified the following brominated flame retardant chemicals using GC/ECNI-MS methods: hexabromocyclododecane (ΣHBCD), bis(2,4,6,-tribromphenoxy)ethane (BTBPE), decabromodiphenyl ethane (DBDPE), and the brominated components found in Firemaster 550 (FM 550): 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB) and (2-ethylhexyl) tetrabromophthalate (TBPH), the latter compound being a brominated analogue of di(2-ethylhexyl)phthalate (DEHP). The concentrations of all compounds were log-normally distributed and the largest range in concentrations was observed for HBCD (sum of all isomers...
Estimation of pulmonary arterial volume changes in the normal and hypertensive fawn-hooded rat from 3D micro-CT data

In the study of pulmonary vascular remodeling, much can be learned from observing the morphological changes undergone in the pulmonary arteries of the rat lung when exposed to chronic hypoxia or other challenges which elicit a remodeling response. Remodeling effects include thickening of vessel walls, and loss of wall compliance. Morphometric data can be used to localize the hemodynamic and functional consequences. We developed a CT imaging method for measuring the pulmonary arterial tree over a range of pressures in rat lungs. X-ray micro-focal isotropic volumetric imaging of the arterial tree in the intact rat lung provides detailed information on the size, shape and mechanical properties of the arterial network. In this study, we investigate the changes in arterial volume with step changes in pressure for both normoxic and hypoxic Fawn-Hooded (FH) rats. We show that FH rats exposed to hypoxia tend to have reduced arterial volume changes for the same preload when compared to FH controls. A secondary objective of this work is to quantify various phenotypes to better understand the genetic contribution of vascular remodeling in the lungs. This volume estimation method shows promise in high throughput phenotyping, distinguishing differences in the pulmonary hypertensive rat model.
Self-diffusion of linear polymers within microcapsules

We present a new strategy for the heterogenization of catalysts. The strategy relies on the containment of soluble polymers within a polyurea microcapsule. Diffusion ordered spectroscopy and spin−spin relaxation measurements are used to demonstrate that the encapsulated polymer is behaving as if it is in solution, not as a solid. Since the interior polymer behaves as if it is in solution, it should be possible to modify the capsule and polymeric contents separately.
An isolated perfused rat lung preparation for the study of aerosolized drug deposition and absorption.

The isolated, perfused rat lung preparation was modified to allow characterized solid aerosol delivery. Deposition and airway-to-perfusate transfer of disodium fluorescein from 3–4 μm dae solid aerosols were studied under different ventilatory regimes. The lungs inhaled from an aerosol stream of constant concentration via a tracheal cannula. Air displacement from a sealed artificial thorax housing the lungs provided the driving force for inhalation. The lungs were suspended in a physiologically normal position and both left and right sides of the heart were cannulated for constant rate perfusate flow. Fractional deposition was inversely proportional to respiratory frequency implying that sedimentation was the primary deposition mechanism. Increasing tidal volumes similarly enhanced the ratio of amount deposited/amount administered. Fluorescein transfer to the perfusate occurred from the lung regions containing intact vasculature, was apparent first-order, and independent of perfusate flow. The average rate constant for transfer was 0.057 ∓ 0.02 min−1 (t1/2 = 12.2 ∓ 4.2 min−1). The ratio of transferable amount/amount deposited appeared to indicate the depth of aerosol penetration. This increased at high respiratory frequency and tidal volume, while decreasing with increasing aerosol particle size. Potential applications of the model are discussed in the light of these results.
Excitotoxic spinal cord injury: behavioral and morphological characteristics of a central pain model

Intraspinal injections of the AMPA-metabotropic receptor agonist quisqualic acid (QUIS) were made in an effort to simulate injury induced elevations of excitatory amino acids (EAAs), a well documented neurochemical change following spinal cord injury (SCI). The progressive pathological sequela associated with QUIS injections closely resembles the cascade of events described following ischemic and traumatic SCI and the pathogenesis of cavities in the clinical condition of post-traumatic syringomyelia. Using different injection parameters, i.e. depth and volume, to deliver QUIS into the cord the results have shown that the technique of intraspinal injection can be used to produce graded patterns of neuronal loss in specific regions of the spinal gray matter. Furthermore, neuronal loss in the dorsal horn, sparing the superficial laminae, results in the onset of spontaneous (excessive grooming behavior) and evoked (mechanical allodynia and thermal hyperalgesia) behaviors commonly associated with experimental models of chronic neuropathic pain. Thus, the present results provide a morphological correlate of spontaneous and evoked pain related behaviors following excitotoxic SCI. The behavioral characteristics combined with the similarities between QUIS induced injury and the clinical pathology of SCI support the use of the excitotoxic model in studies related to the central mechanism(s) of altered sensation, including pain, following spinal injury.