cssi/SciSciGPT-SciSciNet huggingface dataset:
Phase II trial of the PI3 kinase inhibitor buparlisib (BKM-120) with or without enzalutamide in men with metastatic castration resistant prostate cancer

Abstract Background Phosphatidylinositol-3-kinase (PI3K) and androgen receptor pathway activation is common in metastatic castration resistant prostate cancer (mCRPC). Buparlisib is an oral, pan-class I PI3 kinase inhibitor. Methods This was a multisite single arm phase II trial of buparlisib 100 mg ± enzalutamide daily in men with mCRPC whose disease progressed on or who were not candidates for docetaxel. The primary end-point was the rate of radiographic/clinical progression-free survival (PFS) at 6 months. Results Thirty men were accrued: 67% post-docetaxel; median prostate specific antigen (PSA) was 70 ng/dl, 83% had ≥4 prior therapies for mCRPC; 43% received concurrent enzalutamide. The final 6 month PFS rate was estimated to be 10% (95% confidence interval 2.5–23.6%). Median PFS was 1.9 months and was 3.5 months with concurrent enzalutamide. Median overall survival was 10.6 months. Concurrent enzalutamide led to a five-fold reduction in buparlisib concentrations. PSA declines were observed in 23%; no patients achieved a ≥50% decline, and no radiographic responses were observed. Severe adverse events occurred in four men including respiratory infection and multi-organ failure, urinary tract obstruction, confusion and one seizure in the setting of a new central nervous system (CNS) metastasis. Grade III adverse events were seen in 43% of patients; common toxicities included grade I–II weight loss, diarrhoea, nausea, fatigue, anorexia, rash, hyperglycemia and anxiety/mood disorders. Conclusions Buparlisib did not demonstrate significant activity in men with mCRPC, suggesting that PI3K inhibition is not sufficient to reverse resistant mCRPC progression. Future studies of PI3K pathway inhibitors with concurrent enzalutamide should develop optimal dosing and focus on selected patients more likely to benefit.
Review of Recent Pilot Plant Activities with Concentrated Piperazine

Abstract Concentrated 5 molal (m) piperazine (30 wt% PZ) is a novel solvent being developed by the University of Texas at Austin for CO2 capture from coal-fired power plants. In March 2015, a campaign at the UT Austin Separation Research Program (SRP) pilot plant evaluated the advanced flash stripper configuration with 5 and 8 m PZ. The absorber was operated with two gas rates: 350 and 500 acfm. The liquid to gas ratio (L/G) was varied from 2.3 to 5.0 lb/lb. The in-and-out and pump around spray recycle intercooling were operated at 40 °C. Seventeen runs were operated with 5 m PZ and four runs were completed with 8 m PZ. The lean solvent CO2 concentration was varied from 0.18 to 0.26 mol CO2/mol PZ equivalent. The CO2 removal rate in the absorber was varied from 69 to 97%. The advanced flash stripper was operated at temperatures and pressures that varied from 135 to 149 °C and 4.2 to 7 bar, respectively. The cold rich bypass was varied from 0 to 13% and the warm rich bypass was varied from 17 to 41%. 5 m PZ gives 20% better heat transfer performance than 8 m PZ on the LP cross exchanger and resulted in a lower process heat duty because of lower viscosity. Seventeen runs with optimized rich solvent bypass rates achieved process heat duties from 2.1–2.5 GJ/tonne CO2. This campaign demonstrated that using the advanced flash stripper reduced the energy requirement by 25% compared to the previous two SRP campaigns with the two-stage flash configuration.
A Layered Approach to Specification Authoring, Sharing, and Usage

Compositional reuse of software libraries is important for productivity. To promote reliability and correctness, there must also be a way to compose specifications for reuse. However, specifications cannot be adapted by the use of wrappers in the same ways as code, which leads to specifications being copied and modified. This copying and modification of specifications leads to poor maintainability and technical debt. We propose a system, Spekl, that solves these problems and makes compositional reuse of specifications possible in a way independent of the choice of specification languages and tools. We provide a detailed description of our system as well as provide details on our domain specific language for creating new tools, provide details on how to author new specifications, and demonstrate how Spekl facilitates compositional reuse through specification layering.
A lithospheric perspective on structure and evolution of Precambrian cratons

Keywords Craton, Pre-Cambrian, Lithosphere, age, evolution, tectonics, plate tectonics, Geophysical observations
Phenomenology of ADMs

An approximate deconvolution operator denoted by D is an approximate filter inverse that is accurate on the smooth velocity components and does not magnify the rough components.
Structure and Growth Regulation in Normal, Transformed and Malignant Human Endometrial Cell Cultures

Malignant transformation may have unique aspects for the different cell types from the many different tissues of the body. There are unique features of regulation of growth in different cells and tissues and for fetal or neonatal cells as compared to adult cells. For these reasons it is necessary to look at the unique aspects of malignant transformation in a wide spectrum of human cells in order to discover major common themes that characterize the transformation process. Our goal in the studies that are reported here, is to characterize this process as it occurs in cells of one tissue, the endometrium.
Rational anode design for protonic ceramic fuel cells by a one-step phase inversion method

Abstract A one-step phase inversion method was applied to fabricate an optimized anode structure for protonic ceramic fuel cells (PCFCs). The phase inversion process utilized raw starting chemicals, instead of crystalline BaCe0.7Zr0.1Y0.1Yb0.1O3-δ (BCZYYb) powder in an energy and time saving process. The resulting large and fingerlike pores exhibited enhanced performance as compared to the disordered pores produced by conventional preparation of anode structures using dry pressing methods. The electrochemical performance of the rational designed anode supported cell were 491, 402, 302 and 200 mW cm−2 at 700, 650, 600 and 550 C, respectively, which was nearly twice than the cell with dry pressing anode. An equivalent circuit modeling method was used to separate the anode polarization resistance from the single cell, confirming that the overall cell performance improvements were attributed to microstructural modifications of the anode by the phase inversion process. The one-step phase inversion method demonstrated great promise for improved processing of fuel cells and separation membranes.
Six-Month Outcome of Transient Ischemic Attack and Its Mimics.

Background & Objective: Although the risk of recurrent cerebral ischemia is higher after a transient ischemic attack (TIA), there is limited data on the outcome of TIA mimics. The goal of this study is to compare the 6-month outcome of patients with negative and positive diffusion-weighted imaging (DWI) TIAs (DWI-neg TIA vs. DWI-pos TIA) and also TIA mimics. Methods: We prospectively studied consecutive patients with an initial diagnosis of TIA in our tertiary stroke centers in a two-year period. Every included patient had an initial magnetic resonance (MR) with DWI and one-month, three, and six-month follow-up visits. The primary outcome was defined as the composition of intracerebral hemorrhage, ischemic stroke, TIA, coronary artery disease, and death. Results: Out of 269 patients with the initial diagnosis of TIA, 259 patients (mean age 70.5 ± 15.0 [30-100] years old, 56.8% men) were included in the final analysis. 21 (8.1%, 95% confidence interval [CI] 5.1-12.1%) patients had a composite outcome event within the 6-month follow-up. Five (23.8%) and 13 (61.9%) composite outcome events occurred in the first 30 and 90 days, respectively. Among patients with DWI-neg TIA, the one-month and six-month ischemic stroke rate was 1.5% and 4.6%, respectively. The incidence proportion of composite outcome event was significantly higher among patients who had the diagnosis of DWI-neg TIA compared with those who had the diagnosis of TIA mimics (12.2% vs. 2.1% - relative risk 5.9; 95% CI, 1.4 - 25.2). In our univariable analysis among patients with DWI-neg TIA and DWI-pos TIA, age (P=0.017) was the only factor that was significantly associated with the occurrence of the composite outcome. Conclusion: Our study indicated that the overall six-month rate of the composite outcome among patients DWI-neg TIA, DWI-pos TIA, and TIA mimics were 12.2%, 9.7%, and 2.1%, respectively. Age was the only factor that was significantly associated with the occurrence of the composite outcome.
Repression of Germline Genes in Caenorhabditis elegans Somatic Tissues by H3K9 Dimethylation of Their Promoters

Repression of germline-promoting genes in somatic cells is critical for somatic development and function. To study how germline genes are repressed in somatic tissues, we analyzed key histone modifications in three Caenorhabditis elegans synMuv B mutants, lin-15B, lin-35, and lin-37-all of which display ectopic expression of germline genes in the soma. LIN-35 and LIN-37 are members of the conserved DREAM complex. LIN-15B has been proposed to work with the DREAM complex but has not been shown biochemically to be a member of the complex. We found that, in wild-type worms, synMuv B target genes and germline genes are enriched for the repressive histone modification dimethylation of histone H3 on lysine 9 (H3K9me2) at their promoters. Genes with H3K9me2 promoter localization are evenly distributed across the autosomes, not biased toward autosomal arms, as are the broad H3K9me2 domains. Both synMuv B targets and germline genes display a dramatic reduction of H3K9me2 promoter localization in lin-15B mutants, but much weaker reduction in lin-35 and lin-37 mutants. This difference between lin-15B and DREAM complex mutants likely represents a difference in molecular function for these synMuv B proteins. In support of the pivotal role of H3K9me2 in regulation of germline genes by LIN-15B, global loss of H3K9me2 but not H3K9me3 results in phenotypes similar to synMuv B mutants, high-temperature larval arrest, and ectopic expression of germline genes in the soma. We propose that LIN-15B-driven enrichment of H3K9me2 at promoters of germline genes contributes to repression of those genes in somatic tissues.
"Coronary Confusion" Congenital Anomaly of the Left Main Coronary Artery Presenting as a Myocardial Infarction in a Young Female.

Coronary artery anomalies are rare congenital disorders occurring in 0.3-5.6 % of the population. However, it carries a potential risk of sudden death in young athletes due to the development of premature coronary artery disease. The diagnosis of coronary artery anomalies is usually made incidentally; commonly found while investigating other cardiac conditions. A coronary CT angiography and traditional interventional angiography are the gold standards for diagnosing congenital coronary artery anomalies. Here, we present a case of a 27 year-old female with a history of hypertension and membranous glomerulonephritis with proteinuria presenting with an inferior ST elevation myocardial infarction. Cardiac catheterization revealed an anomalous origin of the left anterior descending artery from the right coronary cusp and absence of the left circumflex artery with a super-dominant right coronary artery. The patient had an occlusion of the right posterior descending artery and the right posterolateral segment. We discuss the clinical diagnosis and intervention of the case along with review of the literature.
Pharmacy involvement in an oral anticancer management program: Drug acquisition and safety in an ambulatory comprehensive care center.

85Background: Oral anticancer agents (OACA) offer benefits of convenience, flexibility and quality of life; however, similar to intravenous therapy, OACA can be prone to medication ordering errors,...
Micrococcal-Nuclease-Triggered On-Demand Release of Vancomycin from Intramedullary Implant Coating Eradicates Staphylococcus aureus Infection in Mouse Femoral Canals

Preventing orthopedic implant-associated bacterial infections remains a critical challenge. Current practices of physically blending high-dose antibiotics with bone cements is known for cytotoxicity while covalently tethering antibiotics to implant surfaces is ineffective in eradicating bacteria from the periprosthetic tissue environment due to the short-range bactericidal actions, which are limited to the implant surface. Here, we covalently functionalize poly(ethylene glycol) dimethacrylate hydrogel coatings with vancomycin via an oligonucleotide linker sensitive to Staphylococcus aureus (S. aureus) micrococcal nuclease (MN) (PEGDMA-Oligo-Vanco). This design enables the timely release of vancomycin in the presence of S. aureus to kill the bacteria both on the implant surface and within the periprosthetic tissue environment. Ti6Al4V intramedullary (IM) pins surface-tethered with dopamine methacrylamide (DopaMA) and uniformly coated with PEGDMA-Oligo-Vanco effectively prevented periprosthetic infections in mouse femoral canals inoculated with bioluminescent S. aureus. Longitudinal bioluminescence monitoring, μCT quantification of femoral bone changes, end point quantification of implant surface bacteria, and histological detection of S. aureus in the periprosthetic tissue environment confirmed rapid and sustained bacterial clearance by the PEGDMA-Oligo-Vanco coating. The observed eradication of bacteria was in stark contrast with the significant bacterial colonization on implants and osteomyelitis development found in the absence of the MN-sensitive bactericidal coating. The effective vancomycin tethering dose presented in this on-demand release strategy was >200 times lower than the typical prophylactic antibiotic contents used in bone cements and may be applied to medical implants and bone/dental cements to prevent periprosthetic infections in high-risk clinical scenarios. This study also supports the timely bactericidal action by MN-triggered release of antibiotics as an effective prophylactic method to bypass the notoriously harder to treat periprosthetic biofilms and osteomyelitis.
A Validation Study of the Career Maturity Inventory Attitude Scale

(1977). A Validation Study of the Career Maturity Inventory Attitude Scale. Measurement and Evaluation in Guidance: Vol. 10, No. 2, pp. 113-116.
Family Management in Childhood Attention Deficit Hyperactivity Disorder: A Qualitative Inquiry.

Abstract Purpose The purpose of this study was to better understand how caregivers and families manage childhood Attention Deficit Hyperactivity Disorder (ADHD) in their everyday lives and explore family management factors most relevant to child outcomes, including the child's daily life, condition management effort, condition management ability, and view of condition impact. Design and methods Cross-sectional data from caregivers (N = 50) of children with ADHD (ages 5–12 years) within a large northeastern city were collected, analyzed, and interpreted using directed content analysis and qualitative methods. This inquiry was part of a larger mixed method study which examined the impact of family management on childhood ADHD and how family management factors were related to children's level of impairment across a spectrum of child functioning. Results Thematic summaries based on qualitative descriptive methods highlighted four aspects of family management including: 1) how caregivers contextualized their child's condition in everyday family life, 2) the significant effort required by caregivers to manage their child's ADHD, 3) how caregivers perceived their ability to manage their child's condition, and 4) the impact of ADHD on their child and family's future. Conclusions Family management is an important concept within pediatric literature and may be extended to further research and practice changes for children with ADHD and their caregivers. Practice implications Pediatric nurses are at the forefront of working with children and families. Understanding caregiver perspectives in regard to family management is important for strengthening collaborative partnerships with families and improving the care of children with ADHD.
Survey and technological analysis of laser and its defense applications

Abstract The laser technology has made remarkable progress over the past couple of decades. It is being widely employed in diverse domains, such as holography, space sciences, spectroscopy, medical sciences, micro and power electronics, industrial engineering, and most distinctively, as directed energy military weapons. Owing to their active transmissions, laser systems are similar to microwave radars to some extent; however, unlike conventional radars, the laser operates at very high frequencies thus making it a potent enabler of narrow-beam and high energy aerial deployments, both in offensive and defensive roles. In modern avionics systems, laser target indicators and beam riders are the most common devices that are used to direct the Laser Guided Weapons (LGW) accurately to the ground targets. Additionally, compact size and outstanding angular resolution of laser-based systems motivate their use for drones and unmanned aerial applications. Moreover, the narrow-beam divergence of laser emissions offers a low probability of intercept, making it a suitable contender for secure transmissions and safety-critical operations. Furthermore, the developments in space sciences and laser technology have given synergistic potential outcomes to use laser systems in space operations. This paper comprehensively reviews laser applications and projects for strategic defense actions on the ground or in space. Additionally, a detailed analysis has been done on recent advancements of the laser technology for target indicators and range-finders. It also reviews the advancements in the field of laser communications for surveillance, its earlier state of the art, and ongoing scientific research and advancements in the domain of high energy directed laser weapons that have revolutionized the evolving military battlefield. Besides offering a comprehensive taxonomy, the paper also critically analyzes some of the recent contributions in the associated domains.
Computational heat transfer with spectral graph theory: Quantitative verification

Abstract The objective of this paper is to quantify the precision of a novel approach for computational heat transfer modeling based on spectral graph theory. Two benchmark heat transfer problems with planar boundaries, for which exact analytical solutions are available, are used to determine the precision of temperature predictions obtained from spectral graph, finite difference (one-dimensional), and finite element (three-dimensional) methods. These studies show that the spectral graph approach captures the temperature trends in the benchmark case studies with error in the range of 2% to 10% depending on the location in the body. These verification studies also provide an approach to calibrate the numerical parameters in the new method. The spectral graph approach is applied for predicting the thermal history of a complex three-dimensional additive manufactured (3D printed) part. The temperature trends in a 50-layer part are computed 2.3 times faster than a commercial finite-element software package, and the results differ by less than 7.5%. Further improvements in the computational speed of the spectral graph approach are expected through code optimization and parallelization. This work has far-reaching practical implications for predicting thermal-induced defects in a variety of manufacturing processes including casting and additive manufacturing.
Justice on the inside: teaching human rights and social justice to the recruit prison officers of the Irish prison service by developing professional integrity

This article will outline the planning, processes, challenges and successes of a unique teaching and training program for over 1000 recruits to the Irish Prison Service (IPS), which initially took ...
The influence of oculomotor function on the optical correction for night myopia

Night myopia is the increase in ocular refraction occurring in low levels of illumination. Although night myopia has been known for centuries, there is still no effective method for prescribing the optimal lens to correct the condition. One difficulty is that the tendency of accommodation to seek its dark focus at low luminance may be opposed by convergence. For example, if there is enough luminance to sustain binocular vision, accommodation is influenced by fusional vergence. Therefore, the best optical compensation for night myopia should depend not only on the dark focus of accommodation, but also on the influence that vergence has on accommodation. The degree to which fusional vergence influences accommodation is known as the convergence accommodation to convergence (CA/C) ratio. Our PURPOSE was to perform an experiment under realistic night myopia conditions (binocular viewing and natural pupils) which would allow us to relate the power of the best optical correction to individual differences in the dark focus of accommodation and CA/C ratio. METHODS. The optimal optical compensation for night myopia was determined by measuring visual acuity under binocular conditions across three luminances (0.04, 0.4, and 4.0 cd/m2) and four lens powers (0.0, -0.5, -1.0, and -1.5 diopters). The dark focus was measured with an infrared optometer, and CA/C ratio was measured with an infrared optometer and eyetracker. Sixteen subjects (mean age 25.4 years) with unaided visual acuity of 20/20 were tested. RESULTS. Regardless of CA/C ratio, the optimal lens power was significantly correlated with dark focus. However, the slope of the regression line relating lens power to dark focus was much steeper for subjects with low CA/C ratios than with high ones. CONCLUSIONS. It appears that variability in night myopia can be explained by intersubject differences in dark focus and CA/C ratio. We found that a lens equal to approximately the full dark focus value optimized vision in subjects with low CA/C ratios, and that a one-half dark focus correction did the same for subjects with high CA/C ratios. In addition, we also found evidence for a previously unknown natural mechanism that appears to limit the amount of night myopia through a non-random association of dark focus and CA/C. This process we termed “night emmetropization” because it appears to result in less night myopia than would be expected if there were only a chance association between CA/C and dark focus.
Review of From petro-nationalism to post-extractivism in Ecuador

Resource radicals: From petro-nationalism to post-extractivism in Ecuador, by Thea Riofrancos. Duke University Press, 2020
In-depth analysis of thyroid cancer mortality.

BACKGROUND There are reports of an increasing thyroid cancer mortality rate. This study aimed to analyze the latest trends in this rate over time and compare findings from different cancer registries. METHODS Thyroid cancer incidence-based mortality (IBM) rates were obtained from the Surveillance, Epidemiology, and End Results (SEER) program, including SEER-9, SEER-13, and SEER-18. The National Center for Health Statistics (NCHS) thyroid cancer mortality rate was acquired for comparison. Statistical analysis was performed using the JoinPoint software. RESULTS NCHS data revealed an overall annual percent change (APC) over 1987 to 2017 of 0.61 (P < .01), and the value was nearly four times greater for males compared to females. The overall IBM APC values for SEER-9, SEER-13, and SEER-18 were also positive and statistically significant (P < .01). CONCLUSIONS The increased thyroid cancer mortality rate observed in previous studies continues to be statistically significant based on updated NCHS and SEER IBM data.
Intensive Behavioral Intervention Units

Intensive behavioral intervention units are clinical settings typically housed within a larger university-based or medical campus that exclusively admit clients referred for the assessment and treatment of severe problem behavior. The urgent and complex nature of these cases places exceptional demands on behavior analysts and requires a unique therapeutic approach and clinical structure to provide safe and effective service delivery. The purpose of this chapter is to orient those interested in pursuing a training experience on an intensive behavioral intervention unit by (a) outlining the requisite skills for effective clinical application, (b) discussing the unique structure of service delivery, (c) describing the specialized training and supervision that goes into managing behavioral staff, and (d) reviewing some considerations for successfully navigating regulatory and funding frameworks.
Phenotypes and prognostic factors in adults with Langerhans cell histiocytosis.

7049Background: Langerhans cell histiocytosis (LCH) can manifest as single system (SS) disease, multisystem (MS) disease, or pulmonary LCH (smoking-related). There is a paucity of data on prognosti...
The design of pressure vessels subjected to thermal stress—III: Thermal shock☆

Abstract The design of pressure vessels that are subjected to a sudden maintained change of temperature at one wall is discussed.
Divided and Drifting: Interactionism and the Neglect of Social Organizational Analyses in Organization Studies

The analysis of organizational phenomena within interactionism has become bifurcated between social organizational analyses and organizational ethnographies. This division has had the effect of allowing organizational ethnographies to more readily contribute to organization studies while marginalizing studies of social organization. The historical conditioning of this development and current evidence for this case is demonstrated through an analysis of the existing literature from the past thirteen years of interactionist organizational research. To end the continued neglect of social organizational analyses in the interdisciplinary field of organization studies the article concludes by suggesting a number of possible inspirations for promoting future research.
Abstract 15840: Electrogram Morphology Recurrence Analysis Identifies Areas of Consistent Activation Directions and Rotor Activity in a Rapid Atrial Pacing Model of Atrial Fibrillation

Introduction: Electrogram morphology recurrence (EMR) analysis is a novel mapping technique which characterizes morphology patterns during atrial fibrillation (AF). Using high resolution electrical mapping, we tested the hypothesis that EMR analysis could identify areas of consistent activation directions and rotor activity in a canine rapid atrial pacing model of AF. Methods: Three weeks of rapid right atrial pacing (600 bpm) was performed in six dogs. A triangular plaque was used to obtain 117 simultaneous bipolar AF electrograms from two right and three left atrial locations. EMR plots for each electrogram recording were created by cross-correlation of each activation waveform with each other. The percentage of the most common morphology (REC%) and the mean cycle length (CL) of activations with the most common morphology (CLR) were computed. Activation pattern for each site was classified as either having stable rotors, passive activity, or chaotic activity. Activation vectors were computed and a vector index (VI) was used to measure vector consistency. Results: Figure A shows an example of an EMR plot map from recordings in the left atrium with red indicating areas of high EMR. The sites with the shortest CL had an average CL of 81±13 ms. The sites with the highest REC% had an average value of 99±2%. The sites with the shortest CLR had an average value of 91±17 ms. REC% was highly correlated with VI (Figure B). Minimum CL was only moderately shorter in rotor sites compared to chaotic and passive sites (Figure C). Maximum REC% was significantly higher in rotors sites than in chaotic sites, but not different from passive sites (Figure D). Minimum CLR in the rotor sites were significantly less than both the chaotic and passive sites (Figure E). Conclusions: EMR analysis is a new mapping technique that correlates well with activation vector consistency and can identify rotor activity. This is a promising method for mapping AF that may identify sources that can be targeted for ablation.
Price-tier competition

Abstract Understanding price-tier competition has recently become an important subject of scholarly inquiry due to its relevance for retailers and manufacturers. Existing findings on price-tier competition demonstrate asymmetries between brands in different price-tiers (i.e., intertier competition). However, portfolios of realistic retailers often consist of multiple brands clustered in price-tiers and many consumers switch within price-tiers (i.e., intratier competition). The author argues that it is necessary to understand intertier competition as distinct from intratier competition to obtain a fuller understanding of brand competition in the market place. By using an analytical framework, the author demonstrates that there are significant differences between intertier competition and intratier competition and within intratier competition depending on whether the competition is within the high price-tier or within the low price-tier. Factors moderating the extent of intertier asymmetry and intratier asymmetry are investigated using the analytical framework as well as numerical simulation. Retailing implications and future research directions are delineated.
BIOSYNTHESIS OF NITRO COMPOUNDS I. Nitrogen and Carbon Requirements for the Biosynthesis of β-Nitropropionic Acid by Penicillium atrovenetum

Shaw, Paul D. (University of Illinois, Urbana), and Nancy Wang. Biosynthesis of nitro compounds. I. Nitrogen and carbon requirements for the biosynthesis of beta-nitropropionic acid by Penicillium atrovenetum. J. Bacteriol. 88:1629-1635. 1964.-beta-Nitropropionic acid was produced by Penicillium atrovenetum when this fungus was grown on a Raulin-Thom medium in shake flasks. The nitro compound was formed in the early stages of growth, and the total amount in the medium decreased when the fungus reached the end of the log phase. When increasing amounts of nitrate were substituted for the ammonia in the growth medium, production of beta-nitropropionic acid decreased. Aspartic acid did not promote the synthesis of the nitro compound unless either ammonium chloride or sodium tartrate was also added to the medium. The addition of small amounts of hydroxylamine or sodium nitrite to the Raulin-Thom medium stimulated beta-nitropropionic acid production to a greater degree on a molar basis than the amount of hydroxylamine or nitrite added. The nature of possible precursors to the nitro group of beta-nitropropionic acid is discussed.
sGC Stimulator Efficacy Beyond Blood Pressure in Dahl-Salt Sensitive Model of Hypertension

Soluble guanylate cyclase (sGC) is an important intracellular receptor that can be activated by sGC stimulators to produce cyclic guanosine monophosphate (cGMP)protein kinase G (PKG) mediated effec...
Data acquisition and conversion circuits; integrate or assemble

Systems designers have repeatedly been told to expect penetration of the data acquisition field by ICs. This promise is unfulfilled; meanwhile, hybrids competing in performance with traditional modular devices have appeared. The cost, performance and technology of assembled (hybrid or modular) converter circuits versus the new breed of monolithic devices will be explored.
Brain organization for language from the perspective of electrical stimulation mapping

A model for the organization of language in the adult humans brain is derived from electrical stimulation mapping of several language-related functions: naming, reading, short-term verbal memory, mimicry of orofacial movements, and phoneme identification during neurosurgical operations under local anesthesia. A common peri-Sylvian cortex for motor and language functions is identified in the language dominant hemisphere, including sites common to sequencing of movements and identification of phonemes that may represent an anatomic substrate for the “motor theory of speech perception.” This is surrounded by sites related to short-term verbal memory, with sites specialized for such language functions as naming or syntax at the interface between these motor and memory areas. Language functions are discretely and differentially localized in association cortex, including some differential localization of the same function, naming, in multiple languages. There is substantial individual variability in the exact location of sites related to a particular function, a variability which can be partly related to the patient's sex and overall language ability and which may depend on prior brain injury and, perhaps subtly, on prior experience. A common “specific alerting response” mechanism for motor and language functions is identified in the lateral thalamus of the language–dominant hemisphere, a mechanism that may select the cortical areas appropriate for a particular language function.
Film Cooling Study of Novel Orthogonal Entrance and Shaped Exit Holes

Film cooling effectiveness depends on several geometrical parameters like location on the airfoil, exit shape, orientation and arrangement of the holes. The focus of this investigation is to propose and explore a new film cooling hole geometry. The adiabatic film cooling effectiveness is determined experimentally, downstream of the exit of the film cooling holes on a flat plate using a steady state IR thermography technique. Coolant holes that are perpendicular to the direction of flow detach from the surface and enhance the heat transfer coefficient on the turbine blade without providing any coolant coverage, while angled holes along the mainstream direction result in superior film cooling effectiveness and lower heat transfer to the surface. The objective of this study is to examine the external cooling effects using coolant holes that are a combination of both angled shaped holes as well as perpendicular holes. The inlet of the coolant hole is kept perpendicular to the direction of flow to enhance the internal side heat transfer coefficient and the exit of the coolant hole is expanded and angled along the mainstream flow to prevent the coolant jet from lifting off from the blade external surface. A total of six different cases with variations in exit shape geometry are investigated at different blowing ratios (BR varying from 0.5 to 2.0). Results suggest that the film cooling effectiveness values obtained from these geometries are comparable with those of conventional angled holes. With the added advantage of enhanced heat transfer coefficient on the coolant channel internal side, as proven earlier by Byerley [3], overall superior cooling is accomplished. Furthermore this shaped hole can be made using the same technology being presently used in the industry.Copyright © 2009 by ASME
Differential classical conditioning of a defensive withdrawal reflex in Aplysia californica

The defensive siphon and gill withdrawal reflex of Aplysia is a simple reflex mediated by a well-defined neural circuit. This reflex exhibits classical conditioning when a weak tactile stimulus to the siphon is used as a conditioned stimulus and a strong shock to the tail is used as an unconditioned stimulus. The siphon withdrawal component of this reflex can be differentially conditioned when stimuli applied to two different sites on the mantle skin (the mantle shelf and the siphon) are used as discriminative stimuli. The differential conditioning can be acquired in a single trial, is retained for more than 24 hours, and increases in strength with increased trials. Differential conditioning can also be produced within the field of innervation of a single cluster of sensory neurons (the LE cluster) since two separate sites on the siphon skin can serve as discriminative stimuli. The finding that two independent afferent inputs that activate a common set of interneurons and motor neurons can be differentially conditioned restricts the possible cellular loci involved in the associative learning.
Collaborative Enhancement of Antibody Binding to Distinct PECAM-1 Epitopes Modulates Endothelial Targeting

Antibodies to platelet endothelial cell adhesion molecule-1 (PECAM-1) facilitate targeted drug delivery to endothelial cells by “vascular immunotargeting.” To define the targeting quantitatively, we investigated the endothelial binding of monoclonal antibodies (mAbs) to extracellular epitopes of PECAM-1. Surprisingly, we have found in human and mouse cell culture models that the endothelial binding of PECAM-directed mAbs and scFv therapeutic fusion protein is increased by co-administration of a paired mAb directed to an adjacent, yet distinct PECAM-1 epitope. This results in significant enhancement of functional activity of a PECAM-1-targeted scFv-thrombomodulin fusion protein generating therapeutic activated Protein C. The “collaborative enhancement” of mAb binding is affirmed in vivo, as manifested by enhanced pulmonary accumulation of intravenously administered radiolabeled PECAM-1 mAb when co-injected with an unlabeled paired mAb in mice. This is the first demonstration of a positive modulatory effect of endothelial binding and vascular immunotargeting provided by the simultaneous binding a paired mAb to adjacent distinct epitopes. The “collaborative enhancement” phenomenon provides a novel paradigm for optimizing the endothelial-targeted delivery of therapeutic agents.
Review: History of the Amyloid Fibril

Rudolph Virchow, in 1854, introduced and popularized the term amyloid to denote a macroscopic tissue abnormality that exhibited a positive iodine staining reaction. Subsequent light microscopic studies with polarizing optics demonstrated the inherent birefringence of amyloid deposits, a property that increased intensely after staining with Congo red dye. In 1959, electron microscopic examination of ultrathin sections of amyloidotic tissues revealed the presence of fibrils, indeterminate in length and, invariably, 80 to 100 A in width. Using the criteria of Congophilia and fibrillar morphology, 20 or more biochemically distinct forms of amyloid have been identified throughout the animal kingdom; each is specifically associated with a unique clinical syndrome. Fibrils, also 80 to 100 A in width, have been isolated from tissue homogenates using differential sedimentation or solubility. X-ray diffraction analysis revealed the fibrils to be ordered in the beta pleated sheet conformation, with the direction of the polypeptide backbone perpendicular to the fibril axis (cross beta structure). Because of the similar dimensions and tinctorial properties of the fibrils extracted from amyloid-laden tissues and amyloid fibrils in tissue sections, they have been assumed to be identical. However, the spatial relationship of proteoglycans and amyloid P component (AP), common to all forms of amyloid, to the putative protein only fibrils in tissues, has been unclear. Recently, it has been suggested that, in situ, amyloid fibrils are composed of proteoglycans and AP as well as amyloid proteins and thus resemble connective tissue microfibrils. Chemical and physical definition of the fibrils in tissues will be needed to relate the in vitro properties of amyloid protein fibrils to the pathogenesis of amyloid fibril formation in vivo.
Vanilloid (Capsaicin) Receptors Influence Inflammatory Sensitivity in Response to Particulate Matter

Abstract The signs of airway inflammation and hyperresponsiveness that occur in animals exposed to air pollutants are often strain- and species-specific. To investigate the underlying causes of this phenomenon, BALB/c and C57bl/6 mice were exposed intratracheally to residual oil fly ash (ROFA, 3 mg/kg) and examined after 24 h for signs of airway inflammation. BALB/c showed significantly higher numbers of neutrophils and increased airway hyperresponsiveness in response to methacholine challenge, whereas B6 mice showed no significant change in either inflammatory endpoint. To determine the underlying cause of this strain specificity, cultures of dorsal root ganglion (DRG) sensory neurons, which innervate the upper airways in situ, were explanted from both BALB/c and B6 fetal mice. After 5–7 days in culture, they were exposed to ROFA, other urban and industrial particulate matter (PM; e.g., oil fly ash, woodstove, Mt. St. Helen, St. Louis, Ottawa, coal fly ash) or to prototype irritants (e.g., capsaicin 3–10 μM, pH 5.0 and 6.5). In all instances (except for woodstove), DRG neurons from BALB/c mice released significantly higher levels of the pro-inflammatory cytokine IL-6 into their nutrient media relative to neurons from B6 mice. This cytokine release could be significantly reduced for all PM treated cultures (except woodstove) by pretreatment of cultures with capsazepine (CPZ), a competitive antagonist of vanilloid receptors. DRG neurons, cultured from BALB/c and B6 neonates, were loaded with Fluo-3 AM and exposed to the prototype irritants, acid pH (5.0, 6.5), or capsaicin (3, 10 μM). Analysis of their increases in intracellular calcium showed that significantly higher numbers of BALB/c neurons responded to these prototype irritants, relative to B6 neurons. Morphometric analysis of BALB/c neurons, histochemically stained with cobalt to label neurons bearing capsaicin-sensitive receptors, showed a significantly higher level of stained neurons relative to B6 neurons. Finally, semiquantitative RT-PCR showed a higher expression of VR1 receptor mRNA in DRG and spinal cord taken from neonatal BALB/c mice relative to B6 mice. Taken together, these data suggest that capsaicin and acid-sensitive irritant receptors, located on somatosensory cell bodies and their nerve fiber terminals, subserve PM-induced airway inflammation and are quantitatively different in responsive and nonresponsive mouse strains.
Closed-loop feedback of MHD instabilities on DIII-D†

A system of coils, sensors and amplifiers has been installed on the DIII-D tokamak to study the physics of feedback stabilization of low-frequency MHD modes such as the resistive wall mode (RWM). Experiments are being performed to assess the effectiveness of this minimal system and benchmark the predictions of theoretical models and codes. In the last campaign the experiments had been extended to a regime where the RWM threshold is lowered by a fast ramp of the plasma current. In these experiments the onset time of the RWM is very reproducible. With this system, the onset of the RWM had been delayed by up to 100 ms without degrading the plasma performance. The growth rate of the mode increases proportional to the length of the delay, suggesting that the plasma is evolving towards a more unstable configuration. The present results have suggested directions for improving the feedback system, including better sensors and improved feedback algorithms.
Dietary copper: A powerful determinant of cholesterolemia

A new hypothesis suggests that deficiency of copper is important in the etiology and pathophysiology of ischemic heart disease. Several chemicals, called cholesterotropic and cuprotropic, that affect cholesterolemia also affect copper metabolism. Responses to some of these chemicals that have been tested in humans were compared on a molar basis. Dietary copper was approximately one hundred times as active in lowering cholesterol in plasma than was clofibrate which, in turn was six times as active as dietary fat. Dietary copper may be a powerful determinent of cholesterolemia.
Correlation between the half-wave reduction potentials of nitroheterocycles and their mutagenicity in Chinese hamster V79 spheroids

Abstract Toxicity and DNA damage by nitroheterocycles has previously been correlated with their redox potentials. Resistance to 6-thioguanine was measured using Chinese hamster V79 cells grown in suspension culture as three-dimensional cell clusters of “spheroids”. Since diffusion gradients of oxygen and other nutrients are largely responsible for the growth properties of spheroids, cells grown as spheroids might better simulate cells exposed to mutagens in vivo. The log of the concentration inducing 10 mutants/plate or 1.6 × 10 5 clonogenic cells from spheroids (equivalent to about 300 rad), was correlated with the half-wave reduction potential of a series of nitroheterocycles. FANFT and 4NQO were more mutagenic than predicted on the basis of redox potential.
AERIAL CIR REMOTE SENSING FOR WEED DENSITY MAPPING IN A SOYBEAN FIELD

Accurate weed maps are essential for the success of site–specific herbicide application using map–based variable–rate sprayers. In this study, remotely sensed images acquired using an airborne digital color infrared (CIR) sensor were used for mapping and modeling the spatial distribution of weed infestation density within a soybean field. The effect of spatial positioning error associated with data on resolution requirements and mapping accuracy was also studied. Vegetative indices developed from the three–band CIR image showed strong correlation with spatial weed density. The best correlation was observed at the spatial resolutions of 4.5 m/pixel to 5.3 m/pixel, which was lower than the actual data resolutions. Higher modeling accuracies observed at lower resolutions were caused by the positioning error associated with both aerial imaging data and ground–truth data. At this resolution, the weed density models developed using an artificial neural network resulted in R 2 values of 0.87 and 0.83. This model mapped the spatial distribution of weed density with an R 2 value of 0.58 for a field not used in modeling.
Morphometric influences on intraoperative core temperature changes.

Intraoperative core hypothermia develops in three characteristic phases:1) core-to-peripheral redistribution of body heat that is most prominent during the first hour after induction of anesthesia; 2) subsequent slow linear decrease in core temperature resulting largely from heat loss exceeding metabolic heat production; and 3) core temperature plateau resulting when thermoregulatory vasoconstriction decreases cutaneous heat loss and constrains metabolic heat to the core thermal compartment. Accordingly, we tested the hypotheses that: 1) core cooling does not depend on body fat (BF) or the ratio of weight-to-surface area (Wt/SA) during the initial redistribution phase; 2) the core cooling rate is a function of the Wt/SA ratio during the second phase; and 3) the rate of core cooling during the plateau phase (after vasoconstriction) will be determined by the percentage of BF. In 40 patients undergoing elective colon surgery, the amount of redistribution hypothermia was inversely proportional to the percentage of BF (Delta TC = 0.034 centered dot BF - 2.2, r2 = 0.63) and the Wt/SA ratio (Delta TC = 0.052 centered dot Wt/SA - 3.35, r2 = 0.66). The core cooled linearly during the second phase, and the cooling rate was inversely proportional to the Wt/SA ratio (rate = 0.035 centered dot (Wt/SA) - 2.2, r2 = 0.29). Thermoregulatory vasoconstriction was effective in virtually all patients independent of their morphology, and produced a fourfold reduction in the core cooling rate. These results indicate that patient morphometric characteristics substantially influence intraoperative core temperature changes, and that the effect depends on the hypothermia phase. (Anesth Analg 1995;80:562-7)
Regulated expression and binding of three VLA (β1) integrin receptors on T cells

Regulated adhesion of T cells to extracellular matrix (ECM) proteins is likely to be essential in T cell migration. Constitutive binding of various other cell types to ECM components is mediated by members of the VLA (very late antigen) subfamily of integrins. We describe here the regulated binding of resting CD4+ human T cells to ECM through three VLA integrins: VLA-4 and VLA-5 binding to fibronectin (FN), and a novel pathway of VLA-6 binding to laminin (LN). Binding to ECM is regulated in two ways. First, unlike other VLA-mediated interactions, VLA binding activity of the T cells is rapidly and dramatically augmented with cell activation without change in level of expression of the VLA molecules. Second, binding is regulated with T-cell differentiation; memory T cells express three- to four-fold more VLA-4, VLA-5, and VLA-6 than do naive cells, and bind more efficiently through them to FN and LN.