cssi/SciSciGPT-SciSciNet huggingface dataset:
Impacts of Feral Horse Use on Herbaceous Riparian Vegetation within a Sagebrush Steppe Ecosystem

ABSTRACT Feral horses inhabit rangeland ecosystems around the world, and their impacts on riparian ecosystems are poorly understood. We characterized impacts of a free-ranging horse population on the structure and composition of riparian plant communities in the sagebrush steppe ecosystem in the western United States. We used a randomized block design with single 25 × 50m exclosures and grazed plots on four study sites within Sheldon National Wildlife Refuge in northwestern Nevada. Exclosures were constructed in 2008. Herbaceous plant utilization was measured from 2009 to 2013 by clipping within excluded and grazed plots. Herbaceous production and vertical structure were measured in 2013, and plant functional group and ground cover components were estimated in 2012–2013. Herbaceous utilization ranged from 27% to 84%, and herbaceous production did not differ by grazing treatment (P = 0.472). Grazed plots had seven-fold higher bare ground cover (P < 0.001), 60% less litter cover (P < 0.001), and the basal c...
Invited Commentary: Searching for the Perfect Measure of Diastolic Dysfunction - A Futile Exercise?

Heart failure with preserved ejection fraction (HFpEF) is common, recalcitrant to treatment, and associated with poor outcomes. Diastolic dysfunction (DD) is an independent predictor of HFpEF risk, associated clinical manifestations, and long-term outcomes. However, the usefulness of diastolic function assessment is limited by the heterogeneity in the existing definitions of DD. In this issue of the Journal, Rasmussen-Torvik et al. (Am J Epidemiol. 2017;185(12):1221-1227) have highlighted this problem by evaluating the prevalence and concordance of 4 established definitions of DD in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. The authors demonstrate significant variability in prevalence of DD and its association with established risk factors across the different definitions. These findings suggest that the current 1-dimensional approach to HFpEF risk prediction based on noninvasive measures of diastolic function may not be optimal. Perhaps the future of HFpEF risk assessment lies in a multimodality approach that combines the relevant echocardiographic measures of diastolic function with blood-based biomarkers (such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP)) and a measure of functional status (such as exercise capacity).
Fewer immigrants have preventable ED visits in the United States.

Abstract Objective The aim of this study is to examine differences in having preventable emergency department (ED) visits between noncitizens, naturalized and US-born citizens in the United States. Methods We linked the 2008–2012 Medical Expenditure Panel Survey with National Health Interview Survey data to draw a nationally representative sample of US adults. Univariate analysis described distribution of preventable ED visits identified by the Prevention Quality Indicators across immigration status. We also assessed the association between preventable ED visits and immigration status, controlling for demographics, socioeconomic status, health service utilization, and health status. We finally applied the Oaxaca-Blinder decomposition method to measure the contribution of each covariate to differences in preventable ED services utilization between US natives, naturalized citizens, and noncitizens. Results Of US natives, 2.1% had any preventable ED visits within the past years as compared to 1.0% of noncitizens and 1.5% of naturalized citizens. Multivariate results also revealed that immigrants groups had significantly lower odds (adjusted OR: naturalized citizen 0.77 [0.61–0.96], noncitizen 0.62 [0.48–0.80]) of having preventable ED visits than natives. Further stratified analysis by insurance status showed these differences were only significant among the uninsured and public insurance groups. Race/ethnicity and health insurance explained about 68% of the difference in preventable ED service utilization between natives and noncitizens. Conclusion Our study documents the existing differences in preventable ED visits across immigration status, and highlights the necessity to explore unmet health needs among immigrants and eliminate disparities.
Predation risk across a dynamic landscape: effects of anthropogenic land use, natural landscape features, and prey distribution

Human-mediated landscape changes alter habitat configuration, which strongly structures animal distributions and interspecific interactions. The effects of anthropogenic disturbance on predator–prey relationships are fundamental to ecology, yet less well understood. We determined where predation events occurred for fawn and adult female mule deer from 2008 to 2014 in critical winter range with extensive energy development. We investigated the relationship between predation sites, energy infrastructure, and natural landscape features across contiguous areas experiencing different degrees of energy extraction during periods of high and low intensity development. We contrast spatial correlates of 286 mortality locations with random landscape locations and mule deer distribution estimated from 350,000 GPS locations. We estimated predation risk with resource selection functions and latent selection difference functions. Relative to the distribution of mule deer, predation risk was lower closer to pipelines and well pads, but higher closer to roads. Predation sites occurred more than expected relative to availability and deer distribution in deeper snow and non-forested habitats. Anthropogenic features had a greater influence on predation sites during the period of low activity than high activity, and natural landscape characteristics had weaker effects relative to anthropogenic features throughout the study. Though canids accounted for the majority of predation events, felids exhibited stronger landscape associations, driving the observed spatial patterns in predation risk to mule deer. The emergence of varied interactions between predation and landscape features across contexts and years highlights the complexity of interspecific interactions in highly modified landscapes.
Costly External Financing and Monetary Policy Transmission: Evidence from a Natural Experiment

I provide new evidence that large and small banks have different external financing costs, which generates cross sectional variation in a deposits market pricing power channel of monetary policy transmission. I do so by exploiting a natural experiment using anti-trust related bank branch divestitures. In these divestitures branches are transferred from large to small banks such that the branches are largely preserved and market structure remains unchanged. Consistent with the existence of capital market imperfections at small banks, I find that - holding market concentration constant - lending declines in areas local to branches newly owned by small banks, and deposit rates increase by more, when interest rates increase. My results are confirmed with geographically granular tests utilizing the entire sample of data, and indicate that financing frictions still matter for the transmission of monetary policy through banks.
Association of WNT Pathway Genes With Nonsyndromic Cleft Lip With or Without Cleft Palate.

Objective:Nonsyndromic cleft lip with or without cleft palate (NSCL±P) is a common craniofacial anomaly with multifactorial etiology. Evidence suggests that variations in WNT pathway genes contribu...
Predicting the performance of linear optical detectors in free space laser communication links

While the fundamental performance limit for optical communications is set by the quantum nature of light, in practical systems background light, dark current, and thermal noise of the electronics also degrade performance. In this paper, we derive a set of equations predicting the performance of PIN diodes and linear mode avalanche photo diodes (APDs) in the presence of such noise sources. Electrons generated by signal, background, and dark current shot noise are well modeled in PIN diodes as Poissonian statistical processes. In APDs, on the other hand, the amplifying effects of the device result in statistics that are distinctly non-Poissonian. Thermal noise is well modeled as Gaussian. In this paper, we appeal to the central limit theorem and treat both the variability of the signal and the sum of noise sources as Gaussian. Comparison against Monte-Carlo simulation of PIN diode performance (where we do model shot noise with draws from a Poissonian distribution) validates the legitimacy of this approximation. On-off keying, M-ary pulse position, and binary differential phase shift keying modulation are modeled. We conclude with examples showing how the equations may be used in a link budget to estimate the performance of optical links using linear receivers.
Surgical management of children and adolescents with upfront completely resected hepatocellular carcinoma.

BACKGROUND Hepatocellular carcinoma (HCC) is an aggressive malignant neoplasm that is often chemoresistant. Complete surgical resection remains the mainstay of therapy. The role of liver transplantation (LT) in pediatric HCC is in evolution, as is the role of adjuvant chemotherapy for stage I disease. METHODS A retrospective review of patients < 18 years of age with completely resected HCC treated with surgical intervention alone at our institution from 2004 to 2015 was conducted. RESULTS Twelve patients with a median age of 12 years (range = 1-17; number of females = 7) with upfront resected HCC (Evans stage I) were identified. Four patients had HCC without identifiable risk factors (fibrolamellar-HCC = 2; early HCC arising in focal nodular hyperplasia = 1, well-differentiated [wd] HCC = 1). Four patients had early or wd-HCC in the context of portosystemic shunts (Abernethy = 2; mesocaval shunt and portal vein thrombosis = 2). Four patients had moderate to wd-HCC in the context of pre-existing liver disease with cirrhosis (progressive familial intrahepatic cholestasis type-2 = 2, alpha-1 antitrypsin deficiency = 1, Alagille syndrome = 1). Seven patients underwent LT (multifocal = 5; solitary = 2); five exceeded Milan criteria (MC) by imaging. Five patients underwent complete resection (segmentectomy = 2; hemihepatectomy = 3). Ten patients received no adjuvant chemotherapy. All patients are alive without evidence of disease with a median follow-up of 54.1 months (range = 28.1-157.7 months). CONCLUSIONS Pediatric and adolescent patients with upfront, completely resected HCC can be effectively treated without chemotherapy. LT should be considered for nonmetastatic HCC, especially in the context of pre-existing chronic liver disease, even when the tumor exceeds MC. Distinct pediatric selection criteria are needed to identify patients most suitable for LT.
Disorders of Excessive Alcohol Intake

Ethanol (CH3CH2OH), also called ethyl alcohol or simply alcohol by most biologists and clinicians, is a primary alcohol. It is soluble both in water and in lipid solvents. Indeed, ethanol is commonly used to extract lipids from tissues. The major industrial source of ethanol is fermentation of glucose or carbohydrates, which can be broken down to glucose. Very little ethanol is produced by metabolic processes in animal cells. The oxidation of 1 g of ethanol in the body to carbon dioxide and water yields 7 kcal of energy and produces 0.9 g of water. In this chapter the metabolism of ethanol (which will also be referred to as alcohol) and the biochemical and clinical effects of excessive intake of alcohol will be considered.
Creating a Democratic Public Sphere Through Political Discussion

Computer-mediated discussion is an increasingly popular method of engaging in political talk with other citizens. This article presents a case study of a Usenet newsgroup focused on abortion, and discusses the creation of a public sphere by the conversants. The notion of the public sphere is discussed, and measures allowing an assessment of its democratic character are proposed. A formula for estimating entropy is developed and applied to data obtained from the case study of an ongoing discussion. A high level of inequality in participation among conversants is noted, with very few of the discussants responsible for an extraordinarily high proportion of the content. This inequality, though tempered by analysis of the newsgroup on a day-to-day basis, calls into question the democratic character of the public sphere represented by this conversation.
The Variability of Depression in Old Age

Although there have been attempts throughout the ages to understand, describe, and treat depression (Jackson, 1986), the word depression continues to be used variably according to context and the predisposing biases of the speaker. Our discussion in this chapter embodies a fluid understanding of depression. Inherent to our constructive position is an appreciation for the heterogeneity of depressive disorders in the elderly. While acknowledging the considerable strides made during the last 20 years in delineating major depression using the categorical methods of the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III; American Psychiatric Association, 1980) and subsequent editions of the DSM, we suggest limits to that framework for the optimal understanding of the vicissitudes of depression in old age. We propose that an optimal understanding of depression in general, but particularly in the elderly, requires a biopsychosocial formulation that is derived and interpreted in the context of a particular, contextually and historically contingent, narrative.
Improved 4D cardiac functional assessment for pediatric patients using motion-weighted image reconstruction.

Our aim was to develop and evaluate a motion-weighted reconstruction technique for improved cardiac function assessment in 4D magnetic resonance imaging (MRI). A flat-topped, two-sided Gaussian kernel was used to weigh k-space data in each target cardiac phase and adjacent two temporal phases during the proposed phase-by-phase reconstruction algorithm. The proposed method (Strategy 3) was used to reconstruct 18 cardiac phases based on data acquired using a previously proposed technique [4D multiphase steady-state imaging with contrast enhancement (MUSIC) technique and its self-gated extension using rotating Cartesian k-space (ROCK-MUSIC) from 12 pediatric patients. As a comparison, the same data set was reconstructed into nine phases using a phase-by-phase method (Strategy 1), 18 phases using view sharing (Strategy 4), and 18 phases using a temporal regularized method (Strategy 2). Regional image sharpness and left ventricle volumetric measurements were used to compare the four reconstructions quantitatively. Strategies 1 and 4 generated significantly sharper images of static structures (P ≤ 0.018) than Strategies 2 and 3 but significantly more blurry (P ≤ 0.021) images of the heart. Left ventricular volumetric measurements from the nine-phase reconstruction (Strategy 1) correlated moderately (r 0.9). The computational burden of Strategy 2 was six times that of Strategy 3. The proposed method of motion-weighted reconstruction improves temporal resolution in 4D cardiac imaging with a clinically practical workflow.
KIFC1 as a novel therapeutic target for p53 mutant colorectal cancer.

e15585Background: Loss or mutation of p53 gene is the most frequent genetic lesion in late-stage colon cancers. The optimal management of p53 mutant (p53M) colorectal cancer (CRC) remains a therape...
Subsonic Dynamic Testing of a Subscale ADEPT Entry Vehicle

The Adaptive Deployable Entry and Placement Technology (ADEPT) is a mechanically-deployed entry system. A sounding rocket test flight of an ADEPT vehicle, known as ADEPT SR-1, was conducted in September 2018. Prior to this sounding rocket test, an investigation was performed using the NASA Langley Research Center 20-ft Vertical Spin Tunnel (VST) to assess the free-flight dynamic characteristics of ADEPT SR-1 at subsonic speeds. The model of ADEPT SR-1 for this VST test was fabricated at 50-percent geometric scale, with dynamically scaled mass properties (Froude scaled) to represent full-scale flight at an altitude of 1.2 km above sea level. The subsonic dynamic characteristics of ADEPT SR-1 were of interest prior to the sounding rocket test because of payload recovery considerations. At low roll rates the model was found to have acceptable dynamic characteristics. It was statically stable in pitch and yaw, exhibiting limit cycle pitch/yaw oscillations of no greater than 20 degrees (the angle between the model’s longitudinal axis and nadir). The model was able to recover from large upsets in pitch and yaw, although if sufficiently provoked it tumbled. Damping in roll was low. At high roll rates the pitch and yaw oscillations grew in magnitude and rate. This behavior was also observed during the sounding rocket flight test.
Flipped Classroom: Applications in Teaching EEG (P3.020)

Objective: To assess the efficacy of the flipped classroom model for teaching typical EEG patterns. To compare learning of those given out of classroom instructional material prior to classroom activities with those who received the instructional material after classroom activities. Background: Interpretation of the electroencephalogram (EEG) often presents a challenge for the neurology resident. Although specific parameters allow them to describe the morphology of waves, the differences can be subtle and often rely on pattern recognition through practice and repetition. This flipped classroom model places the onus on the student to review lecture-based material prior to the classroom, so classroom time can be dedicated to application of learning. Design/Methods: We conducted a randomized crossover study within our neurology residency. Resident were randomized into two groups receiving EEG topic specific reading material prior to or after class. Classroom activity was composed of 60 minutes of active EEG interpretation using an online active multiple choice program with immediate feedback. A clinical neurophysiology trained instructor was present for questions, feedback, and interactive instruction. A 30 question EEG test was used to compare scores before and after the reading and classroom work as well as to compare those given reading material prior to or after classroom activities. Results: Preliminary data after two classroom sessions shows a significant improvement in test scores (0.28+/−0.16 vs. 0.43+/−0.12; P = 0.02). There was no significant difference in post-testing based on whether instructional reading material was provided prior to (0.42+/− 0.1) or after (0.43+/−0.17) classroom activities. Conclusions: The flipped classroom approach can be used to improve resident interpretation of electroencephalograms. Preliminary data suggests there is no difference in efficacy when supplemental material is provided before vs. after the active classroom work. Further data collection is currently ongoing to confirm findings. Disclosure: Dr. Novroski has nothing to disclose. Dr. Correll has nothing to disclose.
Divided by a common language: Musical Theater and popular music studies

Jake Johnson It was either George Bernard Shaw or Oscar Wilde who first said that America and England were divided by a common language. To challenge the inevitability of a similarly entrenched incompatibility within music studies, we organized a symposium to consider one of scholarship's
RIGHT CORONARY ARTERY TO CORONARY SINUS FISTULA PRESENTING WITH ABDOMINAL PAIN

Coronary artery to coronary sinus fistula is a rare cardiac anomaly. We present the case of a male with recurrent abdominal pain found to have this condition. A 35-year-old male presented to the emergency room with complaint of abdominal pain. The patient denied a history of angina or angina
Emission-aware Energy Storage Scheduling for a Greener Grid

Reducing our reliance on carbon-intensive energy sources is vital for reducing the carbon footprint of the electric grid. Although the grid is seeing increasing deployments of clean, renewable sources of energy, a significant portion of the grid demand is still met using traditional carbon-intensive energy sources. In this paper, we study the problem of using energy storage deployed in the grid to reduce the grid's carbon emissions. While energy storage has previously been used for grid optimizations such as peak shaving and smoothing intermittent sources, our insight is to use distributed storage to enable utilities to reduce their reliance on their less efficient and most carbon-intensive power plants and thereby reduce their overall emission footprint. We formulate the problem of emission-aware scheduling of distributed energy storage as an optimization problem, and use a robust optimization approach that is well-suited for handling the uncertainty in load predictions, especially in the presence of intermittent renewables such as solar and wind. We evaluate our approach using a state of the art neural network load forecasting technique and real load traces from a distribution grid with 1,341 homes. Our results show a reduction of >0.5 million kg in annual carbon emissions --- equivalent to a drop of 23.3% in our electric grid emissions.
Continuous-flow manothermosonication treatment of apple-carrot juice blend: Effects on juice quality during storage

Abstract The effect of manothermosonication (MTS) treatment on quality of apple-carrot juice blends during storage was examined in comparison with a high temperature-short time (HTST) treatment. The juice blend (90% apple, 10% carrot) with a pH of 4–4.5 was treated by MTS in a custom-designed sonoreactor (20 kHz and 100% amplitude) at 50 and 60 οC and 200 kPa for 30s or 60s. The quality attributes of the control and the treated juices were compared on days 0, 7, 14, and 21, including brix, turbidity, color, viscosity, pH, titratable acidity (TA), total phenolic content (TPC), and antioxidant capacity. Changes in trace elements of the juice samples were monitored using X-ray fluorescence (XRF) spectrometry. The antioxidant activity of the MTS samples right after treatment and during storage was significantly higher than that of the HTST-treated. No significant differences on TPC and antioxidant capacity were found between the MTS-treated and the control during storage. The TA, Brix, and turbidity of the MTS samples decreased after treatment and during storage whereas a gradual increase in pH was observed in stored juice samples. A better retention of trace elements was observed in the MTS-treated samples than in the HTST ones.
A systematic review of potential screening biomarkers for active TB disease.

Introduction The standard TB Four Symptom Screen does not meet the World Health Organization (WHO) ideal screening criteria for having greater than 90% sensitivity to identify active TB disease, regardless of HIV status. To identify novel screening biomarkers for active TB, we performed a systematic review of any cohort or case-control study reporting associations between screening biomarkers and active TB disease. Methods We searched PubMed and Embase for articles published before October 10, 2021. We included studies from high or medium tuberculosis burden countries. We excluded articles focusing on C-reactive protein and lipoarabinomannan. For all included biomarkers, we calculated sensitivity, specificity and 95% confidence intervals, and assessed study quality using a tool adapted from the QUADAS-2 risk of bias. Results From 8,062 abstracts screened, we included 79 articles. The articles described 302 unique biomarkers, including host antibodies, host proteins, TB antigens, microRNAs, whole blood gene PCRs, and combinations of biomarkers. Of these, 23 biomarkers had sensitivity greater than 90% and specificity greater than 70%, meeting WHO criteria for an ideal screening test. Among the eleven biomarkers described in people living with HIV, only one had a sensitivity greater than 90% and specificity greater than 70% for active TB. Conclusion Further evaluation of biomarkers of active TB should be pursued to accelerate identification of TB disease.
SU-A-210-02: Medical Physics Opportunities at the NRC

The purpose of this student annual meeting is to address topics that are becoming more relevant to medical physicists, but are not frequently addressed, especially for students and trainees just entering the field. The talk is divided into two parts: medical billing and regulations. Hsinshun Wu – Why should we learn radiation oncology billing? Many medical physicists do not like to be involved with medical billing or coding during their career. They believe billing is not their responsibility and sometimes they even refuse to participate in the billing process if given the chance. This presentation will talk about a physicist’s long career and share his own experience that knowing medical billing is not only important and necessary for every young medical physicist, but that good billing knowledge could provide a valuable contribution to his/her medical physics development. Learning Objectives: The audience will learn the basic definition of Current Procedural Terminology (CPT) codes performed in a Radiation Oncology Department. Understand the differences between hospital coding and physician-based or freestanding coding. Apply proper CPT coding for each Radiation Oncology procedure. Each procedure with its specific CPT code will be discussed in detail. The talk will focus on the process of care andmore » use of actual workflow to understand each CPT code. Example coding of a typical Radiation Oncology procedure. Special procedure coding such as brachytherapy, proton therapy, radiosurgery, and SBRT. Maryann Abogunde – Medical physics opportunities at the Nuclear Regulatory Commission (NRC) The NRC’s responsibilities include the regulation of medical uses of byproduct (radioactive) materials and oversight of medical use end-users (licensees) through a combination of regulatory requirements, licensing, safety oversight including inspection and enforcement, operational experience evaluation, and regulatory support activities. This presentation will explore the career options for medical physicists in the NRC, how the NRC interacts with clinical medical physicists, and a physicist’s experience as a regulator. Learning Objectives: Explore non-clinical career pathways for medical physics students and trainees at the Nuclear Regulatory Commission. Overview of NRC medical applications and medical use regulations. Understand the skills needed for physicists as regulators. Abogunde is funded to attend the meeting by her employer, the NRC.« less
The location and expression of idiotypic determinants in the immunoglobulin variable region--II. Chain location of variable region determinants.

Abstract Both myeloma protein 460 and myeloma protein 315 each exhibit two sets of idiotypic determinants. A ‘private’ determinant set which distinguishes protein 460 and protein 315 from each other, and a common or ‘public’ set of idiotypic determinants which are shared by proteins 315 and 460 and which distinguish these two proteins from many other mouse IgA myeloma proteins. One other mouse myeloma protein which shares the ‘public’ idiotype is myeloma protein S.23 which has heavy chain amino acid sequences which resemble in part those of protein 460. Heavy-light chain recombinant molecules of these three proteins were made. The amino acids constituting both the public and private idiotypic markers were located on the heavy chains. The public idiotypic is expressed in recombinatant molecules no matter which light chains were associated with the heavy chains. Antigenic expression of private idiotypes, however, depended on the type of light chain which was present. Modulation of antigenic expression of structural idiotypic determinants by associated chains must be considered when idiotypic determinants are used as genetic markers.
Fibrinolysis Associated with Oncogenic Transformation: MORPHOLOGICAL CORRELATES

Abstract This paper describes some correlations between tumorassociated fibrinolysis and the morphological properties of normal and Simian virus 40 (SV40)-transformed hamster embryo fibroblast cultures. The rate of fibrinolysis and morphological response are both influenced by the nature of the serum supplement; most sera show an excellent correlation between the rate of fibrinolysis and the development of characteristic morphological changes. Both processes require the presence of the serum factor, plasminogen, and its conversion to plasmin. When normal and transformed fibroblasts are co-cultivated under appropriate conditions, the normal cells develop morphological changes similar to those ordinarily expressed by transformed cells. The appearance of these changes in normal cells is also correlated with fibrinolytic activity and the activation of plasminogen. Fibrinolysis and morphological change can be dissociated in media supplemented with sera of bovine origin. When the macromolecular protease inhibitors are destroyed by acid treatment, bovine sera become active in fibrinolysis; however, they do not mediate morphological change, and they can be shown to contain a selective inhibitor of the morphological transformation. These results show that an active fibrinolytic system is a necessary but not a sufficient requirement for morphological changes accompanying transformation of hamster fibroblasts.
Structural Genesis in Wall-Bounded Turbulent Flows

Coherent structures in turbulent flows are usually attributed to patterns of concentrated vorticity. Reynolds averaging is not well suited to the eduction of vortical structures. On the other hand, the averaging that defines the “Generalized Lagrangian Mean” (or GLM) of Andrews and McIntyre captures the mean vortex dynamics in precisely the same way the instantaneous equations of motion describe the instantaneous vorticity dynamics. This suggests advantages might be expected to accrue from the use of this alternative averaging scheme. The possibilities of using the GLM formalism in turbulent flows is discussed, together with other thoughts on coherent structures, which suggest that we may think of the latter as associated with heteroclinic cycles arising from generalized resonances.
A system biology approach for the steady-state analysis of gene signaling networks

The existing approaches used to identify the relevant pathways in a given condition do not consider a number of important biological factors such as magnitude of each gene's expression change, their position and interactions in the given pathways, etc. Recently, an impact analysis approach was proposed that considers these crucial biological factors to analyze regulatory pathways at systems biology level. This approach calculates perturbations induced by each gene in a pathway, and propagates them through the entire pathway to compute an impact factor for the given pathway. Here we propose an alternative approach that uses a linear system to compute the impact factor. Our proposed approach eliminates the possible stability problems when the perturbations are propagated through a pathway that contains positive feedback loops. Additionally, the proposed approach is able to consider the type of genes when calculating the impact factors.
Molecular modeling of the structure and dynamics of the interlayer and surface species of mixed-metal layered hydroxides: Chloride and water in hydrocalumite (Friedel's salt)

The dynamical behavior of Cl− and H2O molecules in the interlayer and on the (001) surface of the Ca-aluminate hydrate hydrocalumite (Friedel’s salt) over a range of temperatures from −100 to 300 ° C was studied using isothermal-isobaric molecular dynamics computer simulations. This phase is currently the best available model compound for other, typically more disordered, mixed-metal layered hydroxides. The computed crystallographic parameters and density are in good agreement with available X-ray diffraction data and the force field developed for these simulations preserves the structure and density to within less than 2% of their measured values. In contrast to the highly ordered arrangement of the interlayer water molecules interpreted from the X-ray data, the simulations reveal significant dynamic disorder in water orientations. At all simulated temperatures, the interlayer water molecules undergo rapid librations (hindered hopping rotations) around an axis essentially perpendicular to the layers. This results in breaking and reformation of hydrogen bonds with the neighboring Cl− anions and in a time-averaged nearly uniaxial symmetry at Cl−, in good agreement with recent 35Cl NMR measurements. Power spectra of translational, librational, and vibrational motions of interlayer and surface Cl− and H2O were calculated as Fourier transforms of the atomic velocity autocorrelation functions and compared with the corresponding spectra and dynamics for a bulk aqueous solution. The ordered interlayer space has significant effects on the motions. Strong electrostatic attraction between interlayer water molecules and Ca atoms in the principal layer makes the Ca· · · OH2 bond direction the preferred axis for interlayer water librations. The calculated diffusion coefficient of Cl− as an outer-sphere surface complex is almost three times that of inner-sphere Cl−, but is still about an order of magnitude less than that of Cl− in bulk aqueous solution at the same temperature.
Acute renal failure: structural-functional correlation.

SummaryThis study evaluates the correlation between renal structural alterations and renal functional impairment 24 hr after induction of oliguric acute renal failure in the rat by intramuscular glycerol injection. The major structural alterations were renal tubular epithelial cell necrosis and plugging of tubular lumens; these were graded as to severity in a blind fashion. Renal functional impairment was estimated by blood urea nitrogen (BUN) measurements. The rats were studied under conditions of varied dietary sodium content resulting in different levels of activity of the renin-angiotensin system which is known to be involved in the pathophysiology of this disorder. Renal structural alterations were severe in the low dietary sodium group, modest in the normal dietary sodium group and least in the high dietary sodium group. Renal functional impairment followed a similar pattern, BUN: low dietary sodium group 165 ± 21 mg%, normal dietary sodium group 75 ± 14 mg%, high dietary sodium group 43 ± 6 mg%. Wh...
Recent insights into the mechanisms of taste transduction and modulation

Abstract An amiloride-sensitive transport system is involved in the taste perception of sodium and lithium salts, as well as sweeteners. Taste can be modulated by purinergic compounds such as inosine monophosphate (IMP), as well as antagonists of adenosine, specifically, methyl xanthines. Kainic acid selectively reduced the taste responses to glutamic acid which suggests that the taste of glutamate is not mediated by the identical receptor population as the so-called ‘primary tastes’.
Generalization in a Stimulus Classification Task: Stimulus Selection Within and Among Dimensions.

Abstract Children's stimulus generalization was investigated in a stimulus classification task. The gradients yielded by this task were unaffected by repeated measurement of individual subjects and therefore did not require averaging over subjects of questionable homogeneity. Experiment I found that systematic individual differences in gradient form occur following exposure to a single dimension value (analogous to traditional single stimulus training). Some subjects were controlled by absolute stimulus properties, some were controlled by relational stimulus properties, and some were not controlled by the experimental dimension. Experiment II found that considerably less intersubject variability occurs following exposure to two dimension values (analogous to traditional discriminative training). Experiment III investigated multidimensional generalization along three dimensions, and the behavior of most of the subjects was accurately described by a model which viewed multidimensional generalization as a process of stimulus selection followed by classification on the basis of all selected dimensions.
Eukaryotic topoisomerase II preferentially cleaves alternating purine-pyrimidine repeats

Alternating purine-pyrimidine sequences (RY repeats) demonstrate considerable homology to the consensus sequence for vertebrate topoisomerase II (Spitzner and Muller (1988) Nucleic Acids Res. 16: 1533-1556). This is shown below and positions that can match are underscored. RYRYRYRYRYRYRYRYRY = alternating purine-pyrimidine 18 bp RNYNNCNNGYNGKTNYNY = topoisomerase II consensus sequence (R is purine, Y is pyrimidine, K is G or T.) Topoisomerase II cleavage reactions were performed (in the absence of inhibitors) on a plasmid containing a 54 base RY repeat and the single strong cleavage site mapped to the RY repeat. Analysis of this DNA on sequencing gels showed that the enzyme cleaved a number of sites, all within the 54 base pair RY repeat. Topoisomerase II also made clustered cleavages within other RY repeats that were examined. Quantitative analysis of homology to the consensus sequence, as measured by the match of a site to a matrix of base proportions from the consensus data base (the matrix mean), showed that both the locations and the frequencies of cleavage sites within RY repeats were proportional to homology scores. However, topoisomerase II cleaved RY repeats preferentially in comparison to non-RY sites with similar homology scores. The activity of the enzyme at RY repeats appears to be proportional to the length of the repeat; additionally, GT, AC and AT repeats were better substrates for cleavage than GC repeats.
Reason, Creativity, and Freedom in Montessori

(1975). Reason, Creativity, and Freedom in Montessori. The Educational Forum: Vol. 40, No. 1, pp. 7-21.
A Yang-Mills theory of gravity implied by general relativity

The weak-field approximation of the general relativity, which is made to fulfil all tests of post-Newtonian gravity, leads to a locally de Sitter invariant Yang-Mills theory of gravity in Minkowski space. As far as the approximations are concerned, the principle of general covariance is equivalent to the principle of local gauge symmetry. Einstein’s theory of general relativity appears to be a classical and zero-spin-density manifestation of this Yang-Mills theory.
Integrative gene expression profiling reveals G6PD-mediated resistance to RNA-directed nucleoside analogues in B-cell neoplasms

The nucleoside analogues 8-amino-adenosine and 8-chloro-adenosine have been investigated in the context of B-lineage lymphoid malignancies by our laboratories due to the selective cytotoxicity they exhibit toward multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and mantle cell lymphoma (MCL) cell lines and primary cells. Encouraging pharmacokinetic and pharmacodynamic properties of 8-chloro-adenosine being documented in an ongoing Phase I trial in CLL provide additional impetus for the study of these promising drugs. In order to foster a deeper understanding of the commonalities between their mechanisms of action and gain insight into specific patient cohorts positioned to achieve maximal benefit from treatment, we devised a novel two-tiered chemoinformatic screen to identify molecular determinants of responsiveness to these compounds. This screen entailed: 1) the elucidation of gene expression patterns highly associated with the anti-tumor activity of 8-chloro-adenosine in the NCI-60 cell line panel, 2) characterization of altered transcript abundances between paired MM and MCL cell lines exhibiting differential susceptibility to 8-amino-adenosine, and 3) integration of the resulting datasets. This approach generated a signature of seven unique genes including G6PD which encodes the rate-determining enzyme of the pentose phosphate pathway (PPP), glucose-6-phosphate dehydrogenase. Bioinformatic analysis of primary cell gene expression data demonstrated that G6PD is frequently overexpressed in MM and CLL, highlighting the potential clinical implications of this finding. Utilizing the paired sensitive and resistant MM and MCL cell lines as a model system, we go on to demonstrate through loss-of-function and gain-of-function studies that elevated G6PD expression is necessary to maintain resistance to 8-amino- and 8-chloro-adenosine but insufficient to induce de novo resistance in sensitive cells. Taken together, these results indicate that G6PD activity antagonizes the cytotoxicity of 8-substituted adenosine analogues and suggests that administration of these agents to patients with B-cell malignancies exhibiting normal levels of G6PD expression may be particularly efficacious.
A new model for characterizing primary creep damage

Primary creep damage may occur at a crack tip in steel at room temperature and below. The effect of this time-dependent damage is generally neglected. Recently developed experimental data clearly show that, for some materials, neglecting time-dependent deformation and damage may be quite nonconservative and dangerous in certain practical applications. In this paper, a new theory is developed which incorporates the effects of time-dependent damage into the crack growth and failure process. The predictive ability of the model is verified first by finite element analyses and then by comparison to experimental data. It is clearly shown that, for the material considered here, time-dependent damage effects must be considered or the crack growth process is not adequately accounted for.
Effects of prostaglandin E2, 16,16-dimethyl prostaglandin E2 and a prostaglandin endoperoxide analogue (U-46619) on gastric secretory volume, [H+] and mucus synthesis and secretion in the rat

Abstract The effects of orally administered prostaglandin E2, 16,16-dimethyl prostaglandin E2 and U-46619, an analogue of the prostaglandin endoperoxide PGH2, on gastric secretory volume, acid and mucus were studied in the rat. All of the compounds significantly increased the volume of gastric secretion, mucus secretion, measured as N-acetylneuraminic acid and mucus synthesis measured as the incorporation of [3H]-glucosamine into mucosal glycoprotein; however, only PGE2 and 16,16-dimethyl PGE2 inhibited acid secretion. U-46619, 1.5 mg/kg provided significant protection against ethanol-induced gastric ulcers, an effect that has been previously shown for the other two compounds. These studies provide additional evidence that prostaglandin induced mucosal protection may by related to an effect on mucus and on stimulation of nonparietal cell gastric secretion. Further study of these parameters may be important in the development of antiulcer drugs for long term clinical use.
Modeling of actuators in laminated composite structures

Two global/local finite element modeling procedures are integrated to permit the analysis of localized three-dimensional affects in laminated composite plates with bonded or embedded actuators. The first technique concerns the use of variable kinematic finite elements which are elements that contain several different types of assumed displacement fields. By choosing appropriate terms from the composite displacement field, an entire array of elements with different levels of kinematic complexity can be formed. The different elements can be conveniently connected together in a single domain for global/local analysis. The second technique concerns the use of finite element mesh superposition in which an independent overlay mesh is superimposed on a global mesh to provide localized refinement for regions of interest regardless of the original global mesh topology. Integration of these two ideas yields a very robust, economical analysis tool for global/local analysis of composite laminates.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Coenzyme A-dependent and -independent acyl transfer between dog heart microsomal phospholipids

Abstract We have recently shown that dog heart microsomes catalyze the transfer of acyl groups from the sn-2 position of exogenous phosphatidylcholine to lysophosphatidylethanolamine with strong preference for arachidonate over linoleate (Biochem. Biophys. Res. Commun. 129, 381–388 (1985)). We now report that the addition of 0.5 mM CoA enhances the acyl transfer activity 3–4-fold but reduces the selectivity for arachidonate. Acyl transfer in the absence of CoA exhibits a pH optimum of 7.5–8.5, whereas two pH optima (7.5 and 4.5) are observed in the presence of CoA with transfer activity at pH 4.5 exceeding that of pH 7.5 by 4–5-fold. The plasmalogen (alkenyl) analog of lysophosphatidylethanolamine is an equally effective acyl acceptor in the absence of CoA but less effective in its presence. The microsomal acyl-CoA/ lysophosphatidylethanolamine acyltransferase does not favor arachidonate over linoleate. Therefore, transacylation from phosphatidylcholine may account for the high arachidonate content of dog heart microsomal phosphatidylethanolamine and its plasmalogen analog. In fact, acyl transfer from endogenous lipids to 1-[1′- 14 C] palmitoyl -2- lyso -sn- glycerophosphoethanolamine results in the generation of mostly (over 80%) tetraunsaturated phosphatidylethanolamine. This proportion is reduced by the addition of CoA and, even more, by CoA plus acyl-CoA-generating cofactors. We conclude that in dog heart microsomes, lysophosphatidylethanolamine can be acylated by different mechanisms, of which the CoA-independent transacylase exhibits the greatest acyl selectivity.
Preclinical Pharmacology, Efficacy and Safety of Varenicline in Smoking Cessation and Clinical Utility in High Risk Patients.

Smoking is still the most prominent cause of preventable premature death in the United States and an increasing cause of morbidity and mortality throughout the world. Although the current treatments such as nicotine replacement therapy (NRT) and bupropion are effective, long-term abstinence rates are low. Mechanism studies suggest that the pleasurable effects of smoking are mediated predominantly by nicotine, which activates the brain reward system by activation of brain α4β2 nicotinic acetylcholine receptors (nAChRs). Varenicline is a novel α4β2 nAChR partial agonist and has been found to be even more effective than NRT or bupropion in attenuating smoking satisfaction and in relieving craving and withdrawal symptoms after abstinence. Thus, varenicline has been recently approved to be a first-line medication for smoking cessation in the United States and European countries. Varenicline is generally well tolerated in healthy adult smokers, with the most commonly reported adverse effects being nausea, insomnia, and headache. However, growing postmarketing data has linked varenicline to an increase in neuropsychiatric symptoms such as seizures, suicidal attempts, depression, and psychosis as well as serious injuries potentially relating to unconsciousness, dizziness, visual disturbances, or movement disorders. Therefore, new safety warnings are issued to certain high risk populations, such as patients with mental illness and operators of commercial vehicles and heavy machinery. In particular, pilots, air traffic controllers, truck and bus drivers have been banned from taking varenicline.