cssi/SciSciGPT-SciSciNet huggingface dataset:
The American Way of Intervention

Is there a distinctive American approach to intervention? Contemporary explanations of the causes of intervention focus either on power politics or normative commitments to protect human rights. This paper proposes political culture as an under explored variable in explaining intervention. More specifically, we argue that American political culture, as found in its history and ideology, explains both why the United States intervenes and, crucially, how it intervenes. Building on recent approaches which highlight the illiberal dimensions of American foreign policy (Monten 2005 and Desch 2008), our hypothesis is that American liberalism produces a distinctively illiberal form of intervention, which largely explains why so many American interventions fail. American interventions are characterized by 1) conflicts between professed aims of constructing liberal governments and actual creation of illiberal polities; 2) punitive discourses that focus on individual leaders and regimes; 3) strong aversion to casualties. These three characteristics can be explained, in part, by 1) institutional conflict between the American executive and legislature, leading to a need for grand ideological and threat based justifications that have less basis in local needs 2) ideological assumptions about the natural harmony of political and economic interests both within target states and within the larger international order; 3) an American political identity that assumes ethnic and religious differences can be reconciled through the creation of a democratic constitutional orders. The paper will explore these hypotheses through the following 19th and 20th century American military interventions: Cuba (1898, 1906); Mexico (1914-1918); Vietnam (1959-1975); Panama (1989); and Somalia (1992-1993).
Dietary Fats Differentially Modulate the Expression of Lecithin:Cholesterol Acyltransferase, Apoprotein-A1 and Scavenger Receptor B1 in Rats

In the present study the effects of dietary fat with defined fatty acids on lecithin:cholesterol acyltransferase (LCAT) and apoA-1, the two components of HDL that play a major role in reverse cholesterol transport (RCT), were examined. In addition, the expression of scavenger receptor B1 (SR-B1), the receptor involved in the uptake of HDL core lipids, was also determined under the same conditions in rats fed semisynthetic diets supplemented with triolein (TO), tripalmitin (TP) or menhaden oil (MO). Serum LCAT activity [ micro mol CE/(L.h)] was significantly (P < 0.05) higher in rats fed TO (33 +/- 4) compared with those fed TP (23 +/- 3) or MO (21 +/- 1). The levels of hepatic LCAT mRNA and hepatic SR-B1 receptor protein did not differ between rats fed TP and MO. The triolein diet, on the other hand, increased the induction of hepatic LCAT mRNA and hepatic SR-B1 receptor protein 1.5- to 2-fold. Serum HDL cholesterol concentrations differed among all groups and were 1.30 +/- 0.08, 1.17 +/- 0.10 and 0.91 +/- 0.06 mmol/L for TO-, TP- and MO-fed rats, respectively. Serum apoA-1 levels were significantly higher in TO-fed rats than in the other two groups. The data indicate that TO increases the secretion of HDL and its components (apoA-1 and LCAT), and stimulates the production of hepatic SR-B1 receptor protein. Overall, these results suggest that triolein may promote RCT and thus retard the development of atherosclerosis.
Rhodotorula Keratitis: A Rarely Encountered Ocular Pathogen

Purpose: To describe a case of fungal keratitis involving an atypical organism with confirmatory in vivo confocal microscopy and to review the literature on Rhodotorula keratitis. Methods: Case report and review of the medical literature. Results: A 22-year-old college student was struck in the left eye with a tree branch and subsequently developed pain, redness and photophobia. Upon presentation, visual acuity was 20/200 and there was a large epithelial defect with diffuse stromal inflammation involving the anterior one-third of the cornea. Cultures of the infiltrate were performed for bacterial, viral and fungal organisms that resulted in a positive culture for Rhodotorula mucilaginosa. Fungal elements were confirmed in vivo by confocal microscopy. The patient was treated with voriconazole initially and had amphotericin added once Rhodotorula infection was confirmed. The patient responded well clinically, and one month after therapy was initiated, the corneal infiltrate had resolved leaving mild anterior stromal haze. Upon completion of therapy at three months, the patient was asymptomatic, had a clear cornea and had a best corrected visual acuity of 20/20 in the involved eye. There was no measurable change in his manifest refraction. Conclusions: Prior cases of Rhodotorula keratitis most often required surgical intervention and were associated with poor outcomes. This case shows that Rhodotorula keratitis can be successfully treated with topical antifungal agents if diagnosed early and appropriate treatment is initiated promptly. We report the first case of Rhodotorula keratitis confirmed by in vivo confocal microscopy. This is also the first description of pseudomycelium formation that has not been previously described in vivo, a morphological structure that this organism rarely demonstrates. Finally, this case shows that confocal microscopy may aid in the early diagnosis and management of fungal keratitis involving this rare but potentially damaging organism.
Case-based assessment in an online nursing pharmacotherapy course.

Objective. To implement and evaluate the effectiveness of case-based assessments in an online pharmacotherapy course for nursing students.Design. Four case-based examinations developed in parallel for the midterm and final examinations and designed to address potential barriers to maintaining academic integrity were compared.Assessment. The use of online, case-based assessments was successful in providing 4 parallel examinations that assessed case-based decision making while maintaining academic integrity and minimizing instructor grading burden.Conclusions. Using an online, case-based assessment strategy is effective and feasible for evaluating the clinical application knowledge of nursing students enrolled in a pharmacotherapy course.
Transcriptional effect of aflatoxin B1 on cytosine and/or hypoxanthine containing DNAs.

The effect of aflatoxin Bt (AFB,) on the template function for RNA synthesis of several single and double-stranded synthetic DNAs containing cytosine (C) and/or hypoxanthine (H) bases is studied in vitro. The results indicate that AFB,, after liver microsome activation, strongly inhibits the template function of poly[d(I-C)] and has little, if any, effect on polydI . polydC, polydI, or polydC. This conclusion is reached whether rat liver nuclear free RNA polymerase or E. coli RNA polymerase is used for the transcription. The mechanism of this inhibition is believed mainly due to the inhibition of elongation of RNA synthesis, because autoradiography of the [α-32 P]GTP labeled RNAs after polyacrylamide gel electrophoresis clearly shows that the size of the RNA from AFB1 treated group is dramatically reduced. The evidence that the selective inhibition of poly[d(I-C)] template function is a direct reflection of the binding of AFB1 to poly[d(I-C)] is provided by the use of radioactive [3H]AFB1 for the binding and by spectrum analysis of the appearance of a broad AFB1-DNA adduct peak between 300 nm and 400 nm right after the typical DNA peak at 260 nmn. These data, which are in direct support to our recent report (F.L. Yu, et al., Carcinogenesis, 11, 475–478, 1990), suggest that the binding of AFB1 prefers alternating, double-stranded DNA, and the binding affinity of AFB1 to DNA is greatly reduced when the bases are in either single- or double-stranded homopolymer forms. Furthermore, since AFB1 binds to and inhibits the template function of poly[d(I-C)], these results also suggest that the binding of AFB1 to DNA may not be exclusively limited to guanine as previously assumed.
Hierarchical planning architectures for mobile manipulation tasks in indoor environments

This paper describes a hierarchical planner deployed on a mobile manipulation system. The main idea is a two-level hierarchy combining a global planner which provides rough guidance to a local planner. We place a premium on fast response, so the global planner achieves speed by using a very rough approximation of the robot kinematics, and the local planner begins execution of the next action even without considering subsequent actions in detail, instead relying on the guidance of the global planner. The system exhibits few planning delays, and yet is surprisingly effective at planning collision free motions. The system is deployed on HERB [20], combining a Segway mobile platform, a WAM arm, and a Barrett hand. The navigation and manipulation components have been tested on the real robot, and the task of simultaneously approaching and grasping a bottle on a countertop was demonstrated in simulation.
Deficiency of arginine esterase in cystic fibrosis of the pancreas: demonstration of the proteolytic nature of the activity.

Extract: Proteolytic activity, defined as the hydrolysis of peptide bonds involving the carboxyl group of L-arginine, in plasma of patients with cystic fibrosis, heterozygotes, and control subjects has been assayed using a fluorometric method with protamine as the substrate and fluorescamine as the reagent. The mean total proteolytic activity in plasma of patients with cystic fibrosis was approximately one-half the mean total activity in control subjects and heterozygotes. The mean proteolytic activity inhibited by soybean trypsin inhibitor in plasma of patients with cystic fibrosis was approximately one-third that of control subjects and heterozygotes. The relationship of arginine esterase activity to proteolytic activity was investigated. The pH optimum and action of reversible and irreversible inhibitors were similar for both activities, suggesting that the arginine esterase activity and proteolytic activity represent similar catalytic entities. These findings are consistent with our hypothesis that the basic defect in cystic fibrosis may reside in the deficiency of a proteolytic enzyme which results in the accumulation of the various cationic macromolecular “factors” described by other investigators in serum of patients with cystic fibrosis. Speculation: The demonstration of a deficiency of proteolytic activity as assayed by the hydrolysis of protamine, a cationic polypeptide, could explain the presence of ciliotoxic cationic protein or polypeptide factors in serum of patients with cystic fibrosis and may, in some unknown manner, be related to the clinical manifestations of the disease.
Housing density as an indicator of spatial patterns of reported human-wildlife interactions in Northern New York

Abstract Compromises in biodiversity and biotic integrity from human development alter native wildlife communities. Anecdotal evidence suggests that increases in residential development contribute to increases in human–wildlife interactions; however, little empirical research has addressed this issue. We tested whether housing density could be used to indicate patterns of reported human–wildlife interactions in Northern New York. We used a novel application of univariate and bivariate K-functions to assess the spatial relationship of reported human–wildlife interactions along a gradient of housing densities. We found that reported human–wildlife interactions are not completely spatially random in Northern New York State and the reports tend to cluster more in areas dominated by suburban and exurban housing densities compared to areas with urban or wildland housing densities. Low-density developments have unintended ecological consequences including an increase in reported human–wildlife interactions. Further work is needed to determine specific reasons for clustering of reported human–wildlife interactions in suburban and exurban areas. However, planners should consider human–wildlife interactions as a potential negative outcome of low-density development and devise development designs, such as clustering, to reduce future human–wildlife conflicts.
Using Wikipedia to Teach Information Literacy

ABSTRACT Today's college student often starts his research by using a search engine. Because of this, Wikipedia is increasingly becoming the go-to reference resource for the newest generation of students. However, many students do not know about the problems (e.g., vandalism) associated with this tool other than ambiguous warnings from librarians and faculty who say that it should not be used for research. Librarians and faculty should help remove the stigma associated with Wikipedia by embracing this Website and its imperfections as a way to make information literacy instruction valuable for the twenty-first-century student.
Disability Studies in Higher Education.

Disability studies courses and programs can have a positive and transformative effect on disability services, students with disabilities, and the broader campus climate by placing disability issues in social, cultural, and political context.
The excitation of the Na airglow from Coqui Dos rocket and ground‐based observations

On February 20 1998 two rockets were launched from Puerto Rico as part of the Coqui Dos campaign. Data from on-board photometers and ground-based data from a Na lidar and an airglow imager allowed an estimate to be made, using both the TIME-GCM and MSIS models, of the branching coefficient α for the Na airglow emission. Assuming the hydrogen density is within the range predicted by the two models the data are consistent with α being less than 0.05. This value is well below a recent theoretical estimate of 0.67 and also below the nominally accepted value of 0.1 derived from previous aeronomic data.
2-D Entropy and Short-Time Fourier Transform to Leverage GPR Data Analysis Efficiency

Accurate detection of singular region using ground-penetrating radar (GPR) is very useful in assessing roadway pavement, bridge deck concrete structure, and railroad ballast conditions. To locate an object within the large radargram involves extensive computational resources and time, especially when the data of interests only possess a small portion of the whole big data set. Therefore, an efficient GPR signal-processing technique is highly demanded. This paper proposes the use of 2-D entropy analysis to narrow down the data scope to the interested regions, which can considerably reduce computational cost for more sophisticated data postprocessing. Joint time-frequency analysis using short-time Fourier transform is then performed for singular region location detection and refinement. The proposed methodology is tested with different laboratory setups. The analysis results show good agreement with physical configurations.
DNA on trial : the molecular basis of DNA fingerprinting

The use of direct DNA-based testing in forensic analysis has become increasingly common. In the past, genetic identity or similarity could be inferred by comparison of ABO blood groups and other pr...
Sexual response in the patient after hysterectomy: Total abdominal versus supracervical versus vaginal procedure

Objective The present study examines the patient's own appraisal of her sexual responsiveness after hysterectomy.
Postmastectomy Radiation Therapy After TRAM Flap Breast Reconstruction

Postmastectomy chest wall and nodal radiation therapy decreases local recurrence and improves disease-free and overall survival. Immediate transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction after mastectomy has become more common. We report on our experience of irradiating the chest wall and regional lymph nodes after a TRAM flap reconstruction and describe the acute side effects, flap viability, and cosmetic outcome. Between 1995 and 2000, 22 patients with a median age of 47 years (range 27-61 years) received chest wall radiotherapy following mastectomy and immediate pedicled TRAM flap reconstruction. The indication for radiotherapy included tumor size, involved lymph nodes, or positive margins. All patients received chemotherapy before radiotherapy and three patients also received concurrent chemotherapy. The median dose to the chest wall was 50.4 Gy in 28 fractions of 1.8 Gy using a 6 or 4 MV linear accelerator. The patients were all computed tomography (CT) planned in the treatment position. The patients were immobilized using an alpha cradle. Two tangent fields were used to deliver the dose. On alternating days, a customized bolus was applied to the chest wall that spared the central region where the subsequent nipple reconstruction would be performed. All 22 patients completed 90% of the prescribed chest wall radiotherapy dose. Sixty-six percent of the patients received treatment without any treatment breaks. Only 10% of the patients developed desquamation of the TRAM flap skin. Thirty percent developed grade II erythema of the TRAM flap. With median follow-up of 18 months, no TRAM flaps have been lost or required revision. This technique for delivery of radiotherapy to the chest wall in patients who have undergone a mastectomy and immediate TRAM flap reconstruction is well tolerated. The acute toxicity was manageable. There were no TRAM flap losses or revisions performed secondary to the radiotherapy.
A Parametric Investigation of Nozzle Planform and Internal/External Geometry at Transonic Speeds

An experimental investigation of multidisciplinary (scarfed trailing edge) nozzle divergent flap geometry was conducted at transonic speeds in the NASA Langley 16-Foot Transonic Tunnel. The geometric parameters investigated include nozzle planform, nozzle contouring location (internal and/or external), and nozzle area ratio (area ratio 1.2 and 2.0). Data were acquired over a range of Mach Numbers from 0.6 to 1.2, angle-of-attach from 0.0 degree to 9.6 degree and nozzle pressure ratios from 1.0 to 20.0. Results showed that increasing the rate of change internal divergence angle across the width of the nozzle or increasing internal contouring will decrease static, aeropropulsive and thrust removed drag performance regardless of the speed regime. Also, increasing the rate of change in boattail angle across the width of the nozzle or increasing external contouring will provide the lowest thrust removed drag. Scarfing of the nozzle trailing edges reduces the aeropropulsive performance for the most part and adversely affects the nozzle plume shape at higher nozzle pressure ratios thus increasing the thrust removed drag. The effects of contouring were primary in nature and the effects of planform were secondary in nature. Larger losses occur supersonically than subsonically when scarfing of nozzle trailing edges occurs. The single sawtooth nozzle almost always provided lower thrust removed drag than the double sawtooth nozzles regardless the speed regime. If internal contouring is required, the double sawtooth nozzle planform provides better static and aeropropulsive performance than the single sawtooth nozzle and if no internal contouring is required the single sawtooth provides the highest statis and aeropropulsive performance.
Criteria for Selection of an Adsorbent for a Temperature Swing Process: Applied to Purification of an Aliphatic Solvent Contaminated with Aromatic Solutes

Abstract Temperature swing adsorption (TSA) is different in several respects from conventional adsorption. This paper explores the distinctions from the standpoint of adsorbent characteristics. In particular, a fixed-bed TSA process is considered for separating dilute aromatics from aliphatics (e.g., toluene and/or xylene in heptane). Relevant adsorbent characteristics include thermal-exchange capacity and properties that affect dissipative effects, e.g., intraparticle diffusivity, bed permeability, axial dispersion coefficient, and thermal diffusivity. Many of the dissipative effects can be manipulated by adjusting particle size, though trade-offs exist that have no clear-cut technical resolution. The adsorbents considered were silica gel, activated alumina, activated carbon, zeolite 13X, and a polymeric adsorbent (XAD-7). Silica gel was selected due to its superior thermal-exchange capacity. The other properties did not vary enough among the other adsorbents to compensate for their lesser capacities.
Cost-effectiveness of low- and standard dose lansoprazole compared with H2-receptor antagonist (H2RA) and placebo in patients with non-ulcer dyspepsia (NUD)

Cost-effectiveness of low- and standard dose lansoprazole compared with H 2 -receptor antagonist (H 2 RA) and placebo in patients with non-ulcer dyspepsia (NUD)
Suppression of insulin-like growth factor acid-labile subunit expression--a novel mechanism for deoxynivalenol-induced growth retardation.

Consumption of deoxynivalenol (DON), a trichothecene mycotoxin commonly detected in cereal-based foods, causes impaired growth in many animal species. While growth retardation is used as a basis for regulating DON levels in human food, the underlying mechanisms remain poorly understood. Oral exposure of mice to DON rapidly induces multiorgan expression of proinflammatory cytokines, and this is followed by upregulation of several suppressors of cytokine signaling (SOCS), some of which are capable of impairing growth hormone (GH) signaling. The purpose of this study was to test the hypothesis that impairment of the GH axis precedes DON-induced growth retardation in the mouse. Subchronic dietary exposure of young (4-week old) mice to DON (20 ppm) over a period of 2–8 weeks was found to (1) impair weight gain, (2) result in a steady-state plasma DON concentration (40–60 ng/ml), (3) downregulate hepatic insulin-like growth factor acid-labile subunit (IGFALS) mRNA expression, and (4) reduce circulating insulin-like growth factor 1 (IGF1) and IGFALS levels. Acute oral exposure to DON at 0.5–12.5 mg/kg body weight (bw) markedly suppressed hepatic IGFALS mRNA levels within 2 h in a dose-dependent fashion, whereas 0.1 mg/kg bw was without effect. DON-induced IGFALS mRNA upregulation occurred both with and without exogenous GH treatment. These latter effects co-occurred with robust hepatic suppressors of cytokine signaling 3 upregulation. Taken together, these data suggest that oral DON exposure perturbs GH axis by suppressing two clinically relevant growth-related proteins, IGFALS and IGF1. Both have potential to serve as biomarkers of effect in populations exposed to this common foodborne mycotoxin.
Evidence for two types of GABA-containing interneurons in the A-laminae of the cat lateral geniculate nucleus: a double-label HRP and GABA-immunocytochemical study.

Neurons containing GABA immunoreactivity were analyzed in the A-laminae of normal cat LGN and of LGN retrogradely labeled with HRP from the visual cortex. In contrast to retrograde labeling of relay cells, GABA+ cells were devoid of HRP label, providing additional evidence for the interneuronal nature of GABAergic cells in the cat LGN. Cell body area measurements showed that the population of GABA+ cells is composed of a large proportion of small (β) cells and a smaller proportion of medium size (a) cells. The proportion of α GABA+ cells increases from medial to lateral parts of the A-laminae, resembling a similar medio-lateral increase of physiologically defined Y cells and of morphologically defined type 1 cells in these laminae. This suggests that the α and β GABAergic cells are related to the Y and X geniculo-cortical relay cells, respectively.
Experimentally Induced Septic Arthritis in Chimpanzees Infected with Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum

Mycoplasma hominis was isolated in pure culture from septic synovial aspirates from an individual (patient A) during 16 different bouts of exacerbation over a 70-month period of observation. Two isolates, 10(7) and also 10(6) color-changing units (CCU) of the 1620 isolate and 5 x 10(4) CCU of the 1628 isolate, caused inflammation in chimpanzees inoculated intraarticularly. Inflammation was also induced with 10(7) CCU of the 2010B isolate, serovar VII of Ureaplasma urealyticum, recovered from an agammaglobulinemic individual (patient B) with septic polyarthritis and with 3 x 10(6) CCU of the PI-1428 isolate of Mycoplasma pneumoniae. Inflammation persisted for up to 36 days and was self-limiting. The aspirates contained up to 220,000 white blood cells/mm3 and up to 10(7) CCU/mL. There was good correlation between the severity of inflammation and the numbers of organisms, but antibody was not detected in aspirates during the peak severity of disease. As the numbers of organisms, decreased, detectable levels of antibody increased, thus suggesting that antibody may have been bound to antigen. Chimpanzees previously infected with either the 1628 isolate of M. hominis or the 2010B isolate of U. urealyticum were protected on challenge with > 100 times the minimal dose causing arthritis. Chimpanzees showed little or no inflammation when inoculated intraarticularly with 5 x 10(8) CCU of the type strain PG-21 of M. hominis or with the type strain CO of U. urealyticum or when inoculated intravenously with 3 x 10(8) CCU of the arthrogenic 1620 isolate of M. hominis.
Comparison of equilibrium ion density distribution and trapping force in penning, Paul, and combined ion traps

Starting from the classical Boltzmann distribution, we obtain the ion density distribution in the limit of either high temperature/low density (Coulomb interaction energy much less than ion kinetic energy) or low temperature/high density (kinetic energy much less than Coulomb interaction energy), and the trapping force for an ion cloud in Penning ion cyclotron resonance, Paul (quadrupole), and combined (Paul trap in a uniform axial static magnetic field) traps. At equilibrium (total angular momentum conserved), the ion cloud rotates at a constant frequency in Penning and combined traps. In a Penning trap, the maximum ion density is proportional to B2/m (B is magnetic field and m is the mass of ions), whereas the maximum ion density in a Paul trap is proportional to (Vrf2/mΩ2r04), with Mathieu equation axial q value <0.4 to satisfy the pseudopotential approximation. Ion maximum densities in both Penning and Paul ion traps depend on the trapping field (magnetic or electric) and ion mass, but not on ion charge. In a Penning trap at maximum ion density (zero pressure), the radial (but not the axial) trapping potential is mass dependent, whereas both radial and axial potentials in a Paul trap at maximum ion density are mass dependent.
Genomic data reveal Toxoplasma gondii differentiation mutants are also impaired with respect to switching into a novel extracellular tachyzoite state.

Toxoplasma gondii pathogenesis includes the invasion of host cells by extracellular parasites, replication of intracellular tachyzoites, and differentiation to a latent bradyzoite stage. We present the analysis of seven novel T. gondii insertional mutants that do not undergo normal differentiation to bradyzoites. Microarray quantification of the variation in genome-wide RNA levels for each parasite line and times after induction allowed us to describe states in the normal differentiation process, to analyze mutant lines in the context of these states, and to identify genes that may have roles in initiating the transition from tachyzoite to bradyzoite. Gene expression patterns in wild-type parasites undergoing differentiation suggest a novel extracellular state within the tachyzoite stage. All mutant lines exhibit aberrant regulation of bradyzoite gene expression and notably some of the mutant lines appear to exhibit high proportions of the intracellular tachyzoite state regardless of whether they are intracellular or extracellular. In addition to the genes identified by the insertional mutagenesis screen, mixture model analysis allowed us to identify a small number of genes, in mutants, for which expression patterns could not be accounted for using the three parasite states – genes that may play a mechanistic role in switching from the tachyzoite to bradyzoite stage.
‘Design for power’ of a commercial grade tubular solid oxide fuel cell

Abstract Fuel cell systems must not only be thermodynamically efficient, but cost competitive as well. Since power plant capital costs are typically measured per unit of rated power (i.e., $/kW), one means of attempting an economically attractive product is to “design for power”. A proven model of a commercial grade tubular solid oxide fuel cell (TSOFC) is presented and verified. The model was used to reveal subtle aspects of enhancing power generation. Internal reformation, while beneficial to system size and integration, hinders power generation. Increasing the electrode thicknesses of the TSOFC design can be beneficial to power generation. Finally, decreasing fuel utilization, at a prescribed operating voltage, is also favorable for power generation. These latter trends are explained in view of the common assertions that thinner electrodes and increased fuel utilizations are the means of fuel cell operation enhancement.
Surface Analysis of Radial Lip Seals With Deterministic Micro Cavities on the Shaft

Many approaches have been used to control the reverse pumping effect in radial lip seals. One of those is the use of oriented triangular micro-asperities on the shaft of the seal. This extended abstract presents areal surface parameter measurements from a lip seal with triangular micro-cavities oriented towards the direction of rotation. Surface parameters in the roughness, hybrid and functional groups are presented. The measurements are then discussed and placed in the context of radial lip seal performance.Copyright © 2007 by ASME
Abstract IA11: Cabozantinib (XL-184) and prostate cancer: Preclinical and clinical profile of a novel agent

The evolving understanding of the biology of prostate cancer has fueled therapeutic research with agents targeting androgen signaling, bone microenvironment, apoptosis, and immune modulation amongst others that are being evaluated in clinical trials and an expanding portfolio of FDA approved agents. Metastasis particularly to bone is a hallmark of prostate cancer and reflects the lethal phenotype of the disease. This process is complex and involves interactions between the cancer cell and several elements of the bone microenvironment including osteoblasts, osteoclasts, endothelial cells and cortical bone. The receptor tyrosine kinase MET and its ligand, hepatocyte growth factor (HGF), drive tumor cell invasion and metastasis. Bone metastases are associated with high levels of MET expression. MET and VEGFR2 synergize to promote angiogenesis, and HGF and VEGF direct crosstalk between tumor cells, osteoblasts, and osteoclasts. In prostate cancer, MET overexpression increases with progression and metastasis to bone and lymph nodes and overexpression of HGF has also been reported. Preclinical data suggest that androgen deprivation increases MET expression, and clinically increased plasma levels of HGF in castration resistant disease is associated with decreased overall survival. Cabozantinib is a multi-targeted tyrosine kinase inhibitor (TKI) that simultaneously blocks MET and VEGFR in vivo. In transgenic mouse models it blocks metastatic spread from primary tumors and inhibits prostate xenograft tumor growth in bone. In cell culture studies, cabozantinib elicits a unique profile of effects on bone microenvironment cells, with dose-dependent inhibition of osteoclast differentiation, and biphasic effects on osteoblast differentiation and function. Results from a recently completed phase II trial in 171 patients with progressive metastatic castration resistant prostate cancer indicate that cabozantinib has moderate but manageable toxicities similar to other TKIs with the most common being fatigue, GI and hand and foot syndrome. Cabozantinib had substantial antitumor activity irrespective of prior docetaxel therapy. Specifically it resulted in 68% overall objective disease control at 12 weeks of therapy and 74% measurable disease regression. Of note is the unique and significant observation of a high rate of partial or complete resolution of bone scans which was observed in 76% of patients and was accompanied by pain improvement in patients with pain at baseline and decreases in bloodbased markers of osteoclast and osteoblast activity. The overall median progression free survival was 29 weeks. Several clinical trials are ongoing or planned to better characterize cabozantinib activity and effect. Citation Format: Maha H. Hussain. Cabozantinib (XL-184) and prostate cancer: Preclinical and clinical profile of a novel agent [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA11.
Conserved Active Site Sequences in Arabidopsis Plastid Terminal Oxidase (PTOX) IN VITRO AND IN PLANTA MUTAGENESIS STUDIES

The plastid terminal oxidase (PTOX) is distantly related to the mitochondrial alternative oxidase (AOX). Both are members of the diiron carboxylate quinol oxidase (DOX) class of proteins. PTOX and AOX contain 20 highly conserved amino acids, six of which are Fe-binding ligands. We have previously used in vitro and in planta activity assays to examine the functional importance of the Fe-binding sites. In this report, we conduct alanine-scanning mutagenesis on the 14 other conserved sites using our in vitro and in planta assay procedures. We found that the 14 sites fall into three classes: (i) Ala-139, Pro-142, Glu-171, Asn-174, Leu-179, Pro-216, Ala-230, Asp-287, and Arg-293 are dispensable for activity; (ii) Tyr-234 and Asp-295 are essential for activity; and (iii) Leu-135, His-151, and Tyr-212 are important but not essential for activity. Our data are consistent with the proposed role of some of these residues in active site conformation, substrate binding, and/or catalysis. Titration experiments showed that down-regulation of PTOX to ∼3% of wild-type levels did not compromise plant growth, at least under ambient growth conditions. This suggests that PTOX is normally in excess, especially early in thylakoid membrane biogenesis.
EXPERIMENTAL OBSERVATIONS ON IRRADIATED, NORMAL, AND PARTIALLY PARATHYROIDECTOMIZED RABBITS : III. THE EFFECTS OF INANITION.

The experiments described in the three papers of this series were undertaken to determine if possible the significance of the parathyroid hypertrophy that has repeatedly been found in rabbits after exposure to ultra-violet light. The fact that the hypertrophy was not accompanied by a corresponding increase in blood calcium led us to infer that the upper level of blood calcium concentration is governed by factors independent of parathyroid control, and that the gland hypertrophy under the influence of ultra-violet light might represent a potential functional capacity, or increased factor of safety, to protect the calcium level under conditions of stress or emergency. Partial parathyroidectomy in irradiated rabbits, compared with the same operation in normal controls, resulted in a similar immediate drop in blood calcium; but a more rapid restoration of the calcium level in the irradiated rabbits indicated a more prompt and active response to the emergency on the part of the remaining glands. In the second group of experiments no significant differences were found in the reactions of irradiated, normal, or partially parathyroidectomized rabbits to injections of calcium chloride or of disodium hydrogen phosphate. All three groups of rabbits rapidly eliminated the excess calcium from the blood. Their reactions to large doses of sodium phosphate, given subcutaneously, appeared to be related to phosphate elimination or retention in the individual animals. Those in each group which had phosphate retention in the blood died in acute tetany. So also in the fasting experiments, reported in this paper, no distinctions could be drawn between normal, irradiated, and partially parathyroidectomized rabbits on the basis of their calcium and phosphorus metabolism. Blood calcium was reduced in a similar manner in all three groups of rabbits, and wide individual variations in serum phosphorus levels preclude significant deductions. But the irradiated rabbits suffered disproportionate losses of weight during the fasting period and four of five of them died during the course of the experiment. The deaths of these rabbits are attributed to this more rapid consumption of their own tissues and possibly also to suprarenal injury caused both by fasting and by exposure to ultra-violet light.
Cold pressing of copper single crystals for a large-area doubly focusing monochromator

The design for a large-area doubly focusing neutron monochromator consists of a large number of small square copper single crystals mounted onto thin aluminium blades that both buckle and rotate independently. This avoids the need for large individual alignment mechanisms for each crystal that introduce unacceptably high levels of background. However, it does require that the crystals be oriented such that the diffracting crystallographic planes are parallel to the crystal face. Cold pressing broadens the natural narrow mosaic of the virgin crystal discs to increase the diffracted intensity. This introduces anisotropy into the crystal that determines its orientation in the final monochromator. The alignment procedure used for each crystal before cutting out the square tile in the correct orientation is described. A few crystals are characterized in detail by neutron diffraction at various stages of the operation, revealing the variation in the mosaic width and the angular position of the reciprocal-lattice vector as a function of the azimuthal angle by rotating the crystal about the normal to its face. The twofold symmetry of the mosaic width of the pressed crystal is modulated by the 2π periodicity introduced by the precession of the reciprocal-lattice vector around the crystal face normal. Satisfactorily aligned crystals have a variation in the angular position for diffraction within the allowed tolerance.
Parents’ Strategies to Elicit Autobiographical Memories in Autism Spectrum Disorders, Developmental Language Disorders and Typically Developing Children

Conversations about the past support the development of autobiographical memory. Parents' strategies to elicit child's participation and recall during past event conversations were compared across three school-age diagnostic groups: autism spectrum disorder (ASD, n = 11), developmental language disorders (n = 11) and typically developing (TD, n = 11). We focused on the prevalence of directives versus enrichment of events. Groups did not differ in number of events, length, and total turns. However, parents of children with ASD produced more direct questions, corrections, and unrelated turns than parents of TD children. Results highlight how parents adjusted their conversational style to their child's communication difficulties to maximize interactions and how these strategies may affect the development of personal conversations.
The memory behavior of cache oblivious stencil computations

We present and evaluate a cache oblivious algorithm for stencil computations, which arise for example in finite-difference methods. Our algorithm applies to arbitrary stencils in n-dimensional spaces. On an "ideal cache" of size Z, our algorithm saves a factor of ?(Z 1/n ) cache misses compared to a naive algorithm, and it exploits temporal locality optimally throughout the entire memory hierarchy. We evaluate our algorithm in terms of the number of cache misses, and demonstrate that the memory behavior agrees with our theoretical predictions. Our experimental evaluation is based on a finite-difference solution of a heat diffusion problem, as well as a Gauss-Seidel iteration and a 2-dimensional LBMHD program, both reformulated as cache oblivious stencil computations.
Fusion of PDGF receptor β to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation

Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome characterized by abnormal clonal myeloid proliferation and by progression to acute myelogenous leukemia (AML). CMML thus offers an opportunity to study early genetic events in the transition to AML. A recently recognized subgroup of CMML has a t(5;12)(q33;p13) balanced translocation. We report that the consequence of the t(5;12) translocation is expression of a fusion transcript in which the tyrosine kinase domain of the platelet-derived growth factor receptor beta (PDGFR beta) on chromosome 5 is coupled to a novel ets-like gene, tel, on chromosome 12. The tel-PDGFR beta fusion demonstrates the oncogenic potential of PDGFR beta and may provide a paradigm for early events in the pathogenesis of AML.
Optical (Hyper) Polarizabilities of Small Silicon Clusters

Electronic contributions to the optical (hyper)polarizabilities of small silicon clusters are theoretically determined. Geometries and the electronic structures of the clusters are established using the tight-binding model. The nonlinear polarizabilities are found to depend primarily on the symmetry of the cluster and prove to be high for the low-symmetry clusters. Possible experiments and applications are discussed.
Tradeoffs in mask architecture: dealing with future illumination angular diversity

Extending EUV lithography to future nodes will lead to significant mask challenges. Higher-NA systems will come with larger angles of incidence on the mask, which further complicate the well-known shadowing problem. Addressing them may require the use of thinner absorbers. At the same time, however, the larger mean angle along with a larger diversity of illumination and diffraction angles can also lead to image and reflectivity degradation. Here we perform a modeling based study to explore the relative importance of these two effects for the 12- and 11-nm half pitch nodes. Specifically, we sacrifice reflectivity for increased angular bandwidth by reducing the number of layers in the multilayer stack to find solutions. We further explore thinner absorber and chirped multilayer designs in an attempt to mitigate these problems. As of the conclusion of this study, we have not been able to achieve any combination of parameters to meet the lithographic requirement of NILS 2.5 over 50nm defocus. We can also expect that any condition that meets this requirement will lead to throughput loss: in the most optimistic case we found reflectivity at 77o and 85o was reduced by 4%, though the lithographic requirement was not yet satisfied.
Substance, relation, and identity

One of the great insights of postmodern thought is that our understanding is perspectival, and that we have the perspectives we do because we have privileged one element of certain important binaries over others. Western civilization, or our understanding of it, is based upon our privileging of the male perspective over the female, the rich over the poor, and the white over the black. If that order were reversed and we privileged the perspective of those who had been marginalized, we would see things very differently.
The Compact Central Object in the RX J0852.0–4622 Supernova Remnant

The central region of the recently discovered supernova remnant (SNR) RX J0852.0-4622 was observed with the Advanced CCD Imaging Spectrometer detector aboard the Chandra X-Ray Observatory. We found only one relatively bright source, about 4' north of the SNR center, with a flux of ~2 × 10-12 ergs s-1 cm-2 in the 0.5-10 keV band. The position of this pointlike source, CXOU J085201.4-461753, rules out its association with the two bright stars in the field, HD 76060 and Wray 16-30. Observations of the field with the Cerro Tololo Inter-American Observatory 0.9 m telescope show a star (R ≈ 17, B ≈ 19) at about 24 from the nominal X-ray position. We consider association of this star with the X-ray source unlikely and estimate a limiting magnitude of the optical counterpart as B ≥ 22.5 and R ≥ 21.0. Based on the X-ray-to-optical flux ratio, we argue that the X-ray source is likely the compact remnant of the supernova explosion that created the RX J0852.0-4622 SNR. The observed X-ray spectrum of the source is softer than spectra of magnetospheric radiation of rotation-powered pulsars, but it is harder than spectra of cooling neutron stars emitting thermal radiation from the entire surface, similar to the central compact source of the Cas A SNR. We suggest that CXOU J085201.4-461753 belongs to the growing family of radio-quiet compact central sources, presumably neutron stars, recently discovered in a number of SNRs.
A globally convergent numerical method for an inverse elliptic problem of optical tomography

A new globally convergent numerical method is developed for an inverse problem for the elliptic equation with the unknown potential. The boundary data simulating measurements in optical tomography are generated by the running source. Global convergence analysis is presented along with numerical experiments.
Acceleration in nitroxide mediated ‘living’ free radical polymerizations

Intramolecular H-bonding has been shown to be a powerful tool in increasing the performance of alkoxyamine initiators for nitroxide mediated living free radical polymerizations.
Sensor failure detection using generalized parity relations for flexible structures

Analytical redundancy may be preferable to hardware redundancy in failure detection/isolation tasks for such large-scale systems as space structures. Generalized single-sensor parity relations are presently applied to this problem; they are noted to yield a very simple isolation logic, and their generation is found to be extremely rapid, even in the case of extremely complex systems, provided only that the eigenstructure of the system be known. Their implementation is, however, extremely sensitive to modeling errors and noise.
Diverse roles of Eph/ephrin signaling in the mouse lens.

Recent genetic studies show that the Eph/ephrin bidirectional signaling pathway is associated with both congenital and age-related cataracts in mice and humans. We have investigated the molecular mechanisms of cataractogenesis and the roles of ephrin-A5 and EphA2 in the lens. Ephrin-A5 knockout (-/-) mice often display anterior polar cataracts while EphA2(-/-) lenses show very mild cortical or nuclear cataracts at weaning age. The anterior polar cataract of ephrin-A5(-/-) lenses is correlated with multilayers of aberrant cells that express alpha smooth muscle actin, a marker for mesenchymal cells. Only select fiber cells are altered in ephrin-A5(-/-) lenses. Moreover, the disruption of membrane-associated β-catenin and E-cadherin junctions is observed in ephrin-A5(-/-) lens central epithelial cells. In contrast, EphA2(-/-) lenses display normal monolayer epithelium while disorganization is apparent in all lens fiber cells. Immunostaining of ephrin-A5 proteins, highly expressed in lens epithelial cells, were not colocalized with EphA2 proteins, mainly expressed in lens fiber cells. Besides the previously reported function of ephrin-A5 in lens fiber cells, this work suggests that ephrin-A5 regulates β-catenin signaling and E-cadherin to prevent lens anterior epithelial cells from undergoing the epithelial-to-mesenchymal transition while EphA2 is essential for controlling the organization of lens fiber cells through an unknown mechanism. Ephrin-A5 and EphA2 likely interacting with other members of Eph/ephrin family to play diverse functions in lens epithelial cells and/or fiber cells.
The application of periodic loading to a ferrite phase shifter design

The use of a class of periodic structures in the design of low-cost ferrite remanence phase shifters is reported. A loading factor is developed to show the relation of device characteristics to the degree of periodic loading. Results of measurements on a sub-array of 64 phase shifters are given to illustrate the repeatability of a described simultaneous assembly technique.