cssi/SciSciGPT-SciSciNet huggingface dataset:
Hierarchical activity clustering analysis for robust graphical structure recovery

In this paper we propose a hierarchical activity clustering methodology which incorporates the use of topological persistence analysis. Our clustering methodology captures the hierarchies present in the data and is therefore able to show the dependencies that exist between these activities. We make use of an aggregate persistence diagram to select robust graphical structures present within the dataset. These models are stable over a bound and provide accurate classification results. This approach allows us to select parameters based on the amount of temporal information needed to maintain high accuracy. The key innovations presented in this paper include the hierarchical characterization of the activities over a temporal parameter as well as the characterization and parameter selection based on stability of the results using persistence analysis.
Architectures for Shared Control of Vehicle Steering

Abstract The allocation of authority between a human driver and an automation system designed to share control with the driver must be managed carefully to ensure safety and driver satisfaction. A driver can tighten grip on a steering wheel, co-contract arm muscles, and change posture to increase authority relative to an automation system that has a finite mechanical impedance. In this paper we develop a system model outfitted with the features required to describe modulating impedance as a means to dynamically allocate authority. We adopt a standard modeling framework, but focus on the description of the driving point impedance of both the driver and the automation system. Haptic feedback from the steering wheel functions both to cue the driver but also to couple the driver biomechanics to the steering and automation system. We also describe a platform designed to support experiments in control sharing with dynamic allocation of authority between two humans, one of them acting as a stand-in for the automation system.
Male Hypogonadism and Liver Disease

Chronic liver disease and cirrhosis are common causes of morbidity and mortality. However, the relationship between sex hormones, most notably testosterone, and liver disease has been examined only in limited studies. Liver disease is generally associated with central hypogonadism, except in the setting of alcoholic liver disease in which ethanol results in testicular damage. There are limited data on the efficacy and safety of treatment of hypogonadism in the setting of liver disease. Data are mixed on improvements in morbidity and mortality with testosterone treatment with improvement in gynecomastia appearing to be the most consistently reported benefit. Although not powered to examine safety outcomes, studies have not demonstrated a clear increase in associated adverse events with testosterone therapy. Liver transplantation is also associated with improvement in testosterone levels in the majority of individuals. However, this finding is not uniform, likely related in part to pre-existing metabolic damage, immunosuppression, graft function, and potentially other comorbidities. Further research is needed on the efficacy and safety of testosterone treatment in liver disease.
Investigating the Influence of Teaching Experience on the Use of ICT in Education

The majority of today’s jobs require sufficient understanding of the new technologies and appropriate computer skills. Therefore, professors need to be qualified to integrate computers in their classroom practices. Actually, teachers are recommended to develop adequate and effective training so as to be able to make successful use of computer technologies in their classrooms. With the advent of the new technologies, learning has become more exciting for learners regardless of their level of education. A lot of studies have revealed that the implementation of ICT in classrooms have come up with many fruitful consequences for both teachers and learners as well. It has increased their willingness to develop their knowledge through these modern tools. Therefore, universities and other educational institutions have realized the value of including computer technologies in instructional processes. This paper aims to explore the impact of teaching experience on the integration of computer technologies in teaching practices. Descriptive analysis of means, and standard deviations were employed to analyse the collected data. Also, inferential statistics, especially the ANOVA test, were used to determine the impact of teaching experience on ICT use for pedagogical objectives. The findings revealed that there are statistically significant differences between professors’ integration of ICT in education based on teaching experience, F(4,158)=20.279,p<0.05.
Ammonia borane with polyvinylpyrrolidone as a hydrogen storage material: Comparison of different molecular weights

Abstract We report thermal and infrared transmission measurements on ammonia borane (NH3BH3, AB), and its bulk composites with polyvinylpyrrolidone (PVP) as a function of temperature. X-ray studies reveal an amorphous phase combined the AB crystalline with the addition of the polymer. We determine the activation energies in the temperature range from 25 °C to 300 °C with various ramp rates via kinetic studies. These activation energies of AB:PVP bulk composites were found to be lower than the pristine AB. Overall, the composites with higher molecular weight and high polymer content revealed the greatest decrease in Ea. The weight loss provided similar results, it decreased from ∼57.8% for AB to ∼10.5% for the polymer composite. The FT-IR studies of AB and the bulk composites showed evidence of the interaction between the boron atom of AB and the oxygen atom of the carbonyl group in PVP. An explanation of the hydrogen release pattern during decomposition at higher temperatures ranging from 25 °C to 300 °C is also provided.
Assessing electronic cigarette effects and regulatory impact: Challenges with user self-reported device power.

Abstract Background Electronic cigarettes (ECIGs) aerosolize liquids for user inhalation that usually contain nicotine. ECIG nicotine emission is determined, in part, by user behavior, liquid nicotine concentration, and electrical power. Whether users are able to report accurately nicotine concentration and device electrical power has not been evaluated. This study’s purpose was to examine if ECIG users could provide data relevant to understanding ECIG nicotine emission, particularly liquid nicotine concentration (mg/ml) as well as battery voltage (V) and heater resistance (ohms, Ω) – needed to calculate power (watts, W). Methods Adult ECIG users (N = 165) were recruited from Los Angeles, CA for research studies examining the effects of ECIG use. We asked all participants who visited the laboratory to report liquid nicotine concentration, V, and Ω. Results Liquid nicotine concentration was reported by 89.7% (mean = 9.5 mg/ml, SD = 7.3), and responses were consistent with the distribution of liquids available in commonly marketed products. The majority could not report voltage (51.5%) or resistance (63.6%). Of the 40 participants (24.8%) who reported voltage and resistance, there was a substantial power range (2.2–32,670 W) the upper limit of which exceeds that of the highest ECIG reported by any user to our knowledge (i.e., 2512 W). If 2512 W is taken as the upper limit, only 30 (18.2%) reported valid results (mean 237.3 W, SD = 370.6; range = 2.2–1705.3 W). Conclusions Laboratory, survey, and other researchers interested in understanding ECIG effects to inform users and policymakers may need to use methods other than user self-report to obtain information regarding device power.
Linear quadratic Gaussian control for resonance damping in microgrids with cascaded converters

Microgrid systems continue to increase both in number and capacity as utilities around the globe look to distributed generation as a potential solution to shrinking generation capacity and rising demand. At the same time, the abundance of renewable resources such as solar and wind coupled with constantly improving technologies to harvest them favor microgrid usage. On the other hand, the deployment of these resources throughout the electric grid has led to a more complex grid networks and cascaded converters at the microgrid level. However, interconnected converters create electrical resonances from conventional LCL filters which create stability concerns. This paper presents the results of using statistical data from a renewable energy solar PV source to design a network-based linear quadratic Gaussian optimal controller (LQG) to minimize resonance effects in a cascaded multi-converter microgrid system. The comparison of its performance with that of an open-loop uncompensated system indicates improvement with inclusion of the LQG controller thus improving generation capacity and reliability. Results are given with respect to an ac microgrid testbed.
Temperature dependence of the helium induced broadening and shift of the Rb D 1 and D 2 lines

Abstract The rates for collisional broadening and shifting of the Rb D1 (52S1/2 – 52P1/2) and D2 (52S1/2 – 52P3/2) transition induced by 4He have been measured at elevated temperatures of 373–723 K. The shift coefficients exhibit an increase of 20% from 4.36 MHz/Torr to 5.35 MHz/Torr for the D1 line and an 80% increase from 0.42 MHz/Torr to 0.99 MHz/Torr for the D2 line over the observed temperature range. Broadening coefficients exhibit a 6% increase from 17.8 MHz/Torr to 18.9 MHz/Torr and 10% from 18.5 MHz/Torr to 20.5 MHz/Torr for the D1 and D2 lines, respectively. The experimental values agree well with prior reported values within the temperature overlap regions of T
Dynamic traffic assignment using the macroscopic fundamental diagram: A Review of vehicular and pedestrian flow models

Abstract Link-level Dynamic Traffic Assignment (DTA) models of large cities may suffer from prohibitive computation times, and calibration/validation can become the major challenge faced in their real-time implementation. The empirical evidence in 2008 in support of the existence of a Macroscopic Fundamental Diagram (MFD) on urban networks led to the formulation of discrete-space DTA models, where the link-level representation of networks replaced by a zone-based representation. In parallel, a large body of DTA models based on Hughes’ pedestrian model have been formulated in continuum space as 2-dimensional conservation laws, where the speed-density relationship has been recently interpreted as a MFD. Unfortunately, today it is not clear whether the continuum-space and discrete-space approaches are consistent with each other, in the sense that a well-defined discrete-space model should correspond to the numerical solution of a continuum model. This paper aims to shed light on this matter by performing a review of the literature in both modeling approaches. We found that (i) the discrete-space DTA models are prone to stalling problem leading to unrealistic gridlocks, (ii) with the exception of Hanseler’s pedestrian models, existing discrete-space models are not guaranteed to be consistent with a continuum formulation, which presents the potential for significant biases between the two approaches although they are trying to answer the same question, (iii) the speed-density relationships used in the continuum-space literature are very simplistic and do not incorporate the effects of network, particularly the effects of intersections, which is the strong suit of the MFD, (iv) the models mostly have been applied to the cases with only one or a few destinations and do not seem to be capable of modeling large-scale networks. We also found that further research is needed to (i) incorporate departure time choice, (ii) improve existing numerical methods, possibly extending recent advances on the one-dimensional kinematic wave (LWR) model, (iii) study the properties of system optimum solutions, (iv) examine the real-time applicability of current continuum-space models compared to traditional DTA methods, and (v) formulate anisotropic models for the interaction of intersecting flows.
The Impact of Decreased Capacity to Experience Pleasure on Leisure Coping Strategies among Individuals with Major Depressive Disorder

Anhedonia is a key clinical feature of major depressive disorder (MDD) and affects one's capacity to experience pleasure. This study examined the extent to which anhedonia disrupts the use and the ...
The significance of DNA technology in medicine.

The foundations of the science of genetics were laid last century by the Augustinian monk Gregor Mendel [1]. As a result of his experiments in cross-breeding peas and beans, he observed that the inheritance of single traits can be explained by genetic factors which are passed on from one generation to the next. At the suggestion of Johannsen (1908) these fundamental units of heredity were named genes. Modern recombinant DNA techniques allow the genes in the complex human genome to be identified and mapped, and permits the analysis of their fine structure. Modern molecular human genetics is also known as “new genetics” [2].
Clash of Logics, Crisis of Trust: Entering the Era of Public For-Profit Health Care?

This chapter investigates four institutional logics that influence the health care field – public, private, nonprofit, and for-profit – and how these logics affect the multiple layers and issues of trust inherent in health care. Pairings of these logics demonstrate a historical progression in the US health care field, from an era of professional involvement following World War II (Scott et al. Institutional change and healthcare organizations: from professional dominance to managed care. Chicago, IL: University of Chicago Press, 2000) and characterized by a private nonprofit logic, to an era of federal involvement beginning in 1965 and characterized by a public nonprofit logic, to an era of managerial control in market mechanisms, beginning in the early 1980s and characterized by a private for-profit logic. Whether or not we are entering a fourth stage – an era characterized by a public for-profit logic – is considered, as well as this logic’s implications for restoring trust in the US health care system. The chapter ends with a discussion of potential directions for future research.
Opposing effects of prostaglandin receptor EP2 signaling in mouse immune cells and neurons after status epilepticus

A multidimensional inflammatory response ensues after status epilepticus (SE), driven partly by cyclooxygenase-2 mediated activation of prostaglandin EP2 receptors. Here we identify those effects of EP2 antagonism that are reproduced by conditional ablation of EP2 receptors in immune myeloid cells and forebrain neurons. Removal of myeloid cell EP2 dampened induction of hippocampal IL-6, prevented erosion of the blood-brain barrier, accelerated weight regain, and relieved ptosis following SE. Elimination of EP2 receptor from neurons enhanced neuronal injury, elevated hippocampal induction of the pro-inflammatory cytokines, TNFα and Ccl2, promoted deterioration of the blood-brain barrier, delayed weight recovery, and worsened animal posture and activity. Taken together these data highlight the complexities in neuroinflammatory signaling, wherein activation of EP2 receptors in innate immune cells is deleterious but neuronal EP2 signaling is protective. Effective treatments targeting brain prostaglandin signaling pathways should be cell targeted to be optimally effective.
Narcissism and Spirituality: Intersections of Self, Superiority, and the Search for the Sacred

Narcissism and narcissistic traits are known to affect various aspects of human functioning, with such traits often being associated with problematic outcomes in social, professional, and interpersonal domains. Another area in which narcissism seems to have some negative consequences is in spiritual functioning. Oftentimes, individuals, regardless of narcissistic traits, may experience difficulties in religious and spiritual functioning, known as religious and spiritual struggles. Although research in this domain is still burgeoning, recent research suggests that narcissism and narcissistic traits—especially trait entitlement—are associated with difficulties in religious and spiritual functioning such as religious and spiritual struggles. The present chapter reviews existing literature related to narcissism and religious and spiritual functioning, with a specific focus on how religious and spiritual struggles are associated with such traits. Links between narcissism and specific struggles (i.e., struggles with deity such as anger at God; interpersonal religious and spiritual struggles, such as conflicts over religion) are explored, and directions for future research are posited.
Cesare Lombroso and the origins of criminology: Rethinking criminological tradition

Cesare Lombroso (1835-1909) is widely recognized as one of the first people to bring scientific methods to bear on the study of crime. A physician, psychiatrist, and prolific author, Lombroso is best known as the founder of criminal anthropology, the study of the body, mind, and habits of the “born” criminal. Lombroso's theory of the atavistic offender dominated criminological discussions in Europe, North and South America, and parts of Asia from the 1880s into the early twentieth century. But critics attacked his theory even during his lifetime, and by the time he died, criminologists outside Italy had moved on to other explanations of crime
Effects of food-borne ZnO nanoparticles on intestinal microbiota of common carp (Cyprinus carpio L.).

Ingestion of nanoparticles (NPs) with antimicrobial properties may disrupt the balance of intestinal microbiota. To investigate the effects of zinc oxide (ZnO) NPs on intestinal flora, common carp Cyprinus carpio were fed a commercial feed containing 500 mg kg−1 ZnO NPs for 6 weeks and compared to a control group receiving a similar feed-only regime. Sequencing data were analyzed both in individual fish and in pooled samples. Sequencing of 16S rRNA encoding gene of individual specimens revealed high variation in intestinal microbial composition. Assessment of pooled results can obscure high individual variation in data. ZnO NPs consumption was not associated with a significant difference in the intestinal microbial community compared to untreated controls. Our results indicated a high individual variation in the intestinal microbiome, which may further point out the importance of functional study over microbial composition to address nanomaterials-microbiome relationship.
Detection of chemical exchange in methyl groups of macromolecules.

The zero- and double-quantum methyl TROSY Hahn-echo and the methyl 1H–1H dipole–dipole cross-correlation nuclear magnetic resonance experiments enable estimation of multiple quantum chemical exchange broadening in methyl groups in proteins. The two relaxation rate constants are established to be linearly dependent using molecular dynamics simulations and empirical analysis of experimental data. This relationship allows chemical exchange broadening to be recognized as an increase in the Hahn-echo relaxation rate constant. The approach is illustrated by analyzing relaxation data collected at three temperatures for E. coli ribonuclease HI and by analyzing relaxation data collected for different cofactor and substrate complexes of E. coli AlkB.
Eigenvalue repulsion and eigenvector localization in sparse non-Hermitian random matrices

Complex networks with directed, local interactions are ubiquitous in nature and often occur with probabilistic connections due to both intrinsic stochasticity and disordered environments. Sparse non-Hermitian random matrices arise naturally in this context and are key to describing statistical properties of the nonequilibrium dynamics that emerges from interactions within the network structure. Here we study one-dimensional (1D) spatial structures and focus on sparse non-Hermitian random matrices in the spirit of tight-binding models in solid state physics. We first investigate two-point eigenvalue correlations in the complex plane for sparse non-Hermitian random matrices using methods developed for the statistical mechanics of inhomogeneous two-dimensional interacting particles. We find that eigenvalue repulsion in the complex plane directly correlates with eigenvector delocalization. In addition, for 1D chains and rings with both disordered nearest-neighbor connections and self-interactions, the self-interaction disorder tends to decorrelate eigenvalues and localize eigenvectors more than simple hopping disorder. However, remarkable resistance to eigenvector localization by disorder is provided by large cycles, such as those embodied in 1D periodic boundary conditions under strong directional bias. The directional bias also spatially separates the left and right eigenvectors, leading to interesting dynamics in excitation and response. These phenomena have important implications for asymmetric random networks and highlight a need for mathematical tools to describe and understand them analytically.
Drone-Based Forest Propagation Measurements for Ground-to-Air EMI Applications

This letter describes measurements of path loss caused by a leafless, mid-Atlantic deciduous forest on ground-to-air (G-A) paths using a drone-based measurement system. The focus of these measurements is on slant paths with low elevation angles (<10°) and large foliage depths (up to 500 m) for G-A electromagnetic interference environments involving interference from large numbers of cell phone uplink emissions at military aircraft sharing the same band. Measurements of excess foliage attenuation versus foliage depth are compared to various models, some of which have not appeared in the literature previously. A particularly simple model for predicting forest attenuation on slant paths at low elevation angles is presented that compares favorably with the measurements.
Hierarchically 3D Porous Ag Nanostructures Derived from Silver Benzenethiolate Nanoboxes: Enabling CO2 Reduction with a Near-Unity Selectivity and Mass-Specific Current Density over 500 A/g

Silver nanostructures with hierarchical porosities of multiple length scales have been synthesized through electrochemical reduction of silver benzenethiolate nanoboxes. The porous Ag nanostructures exhibit superior catalytic performance toward electrochemical reduction of CO2. The Faradaic efficiency of reducing CO2 to CO can be close to 100% at high cathodic potentials, benefiting from the readsorbed benzenethiolate ions on the Ag surface that can suppress the hydrogen evolution reaction (HER). Density functional theory calculations using the SCAN functional reveal that the disfavored H binding on the benzenethiolate-modified Ag surface is responsible for inhibiting the HER. The mass-specific activity of CO2 reduction can be over 500 A/g because the multiple-scale porosities maximize the diffusion of reactive species to and away from the Ag surface. The unique multiscale porosities and surface modification of the as-synthesized Ag nanostructures make them a class of promising catalysts for electrochemical reduction of CO2 in protic electrolytes to achieve maximum activity and selectivity.
Original ContributionsEvaluation of the usefulness of testing for p53 mutations in colorectal cancer surveillance for ulcerative colitis

Objective: Immunohistochemical staining for p53 suppressor gene mutations is sensitive and, therefore, has potential for use as a complementary test for dysplasia to improve ulcerative colitis (UC) cancer surveillance program performance. Methods: A cohort of 95 patients with long standing pan-UC enrolled in a surveillance program was studied. Archival colonic biopsy specimens were stained for p53 mutations and clinical information was obtained from medical records. Results: The 37 patients who developed p53 mutations were significantly more likely to develop dysplasia or cancer (relative risk [RR] 4.53, 95% confidence interval [Cl] 2.16–9.48). The p53 mutations developed approximately 8 months before low grade dysplasia, 26 months before high grade dysplasia, and 38 months before cancer. Three of seven cancer patients with p53 mutations had Dukes’ stage C or D, whereas only one of five cancer patients without p53 mutations had Dukes’ C or D; all three patients who died from metastatic cancer had p53 mutations (three of 37 vs 0 of 58, p < 0.03). Folic acid supplementation had a small, significant protective effect for p53 mutations (RR 0.97, Cl 0.94–1.00). Conclusion: p53 Mutations 1) are associated with, and likely precede, dysplasia and cancer, 2) are associated with cancer-related mortality, and 3) may possibly be prevented by folic acid supplementation.
Cholinergic-induced anion secretion in murine jejunal enteroids involves synergy between muscarinic and nicotinic pathways

Acetylcholine induces robust electrogenic anion secretion in mammalian intestine and it has long been hypothesized that it mediates the epithelial response through the M3 and, to a lesser extent, the M1 muscarinic receptors in the mouse. However, nicotinic receptors have recently been identified in intestinal enterocytes by quantitative real-time (qRT)-PCR/RNAseq, although any direct influence on intestinal transport has not been identified. We tested the hypothesis that cholinergic-induced anion secretion in the intestine is a result of both muscarinic and nicotinic pathways that are intrinsic to the intestinal epithelia. We developed a method to generate mouse jejunal enteroid monolayers which were used to measure active electrogenic anion secretion by the Ussing chamber/voltage-clamp technique. Here, we show that the cholinergic agonist carbachol (CCh) and the muscarinic agonist bethanechol (BCh) stimulate short-lived, concentration-dependent anion secretion in the epithelial cell-only enteroid monolayers. The muscarinic antagonist atropine completely inhibited CCh- and BCh-induced secretion, while the nicotinic antagonist hexamethonium reduced the CCh response by ~45%. While nicotine alone did not alter anion secretion, it increased the BCh-induced increase in short-circuit current in a concentration-dependent manner; this synergy was prevented by pretreatment with hexamethonium. In addition to being sensitive to hexamethonium, monolayers express both classes of cholinergic receptor by qRT-PCR, including 13 of 16 nicotinic receptor subunits. Our findings indicate that an interaction between muscarinic and nicotinic agonists synergistically stimulates anion secretion in mouse jejunal epithelial cells and identify a role for epithelial nicotinic receptors in anion secretion.
What Matters When It Comes to Trust in One's Physician: Race/Ethnicity, Sociodemographic Factors, and/or Access to and Experiences with Health Care?

Purpose: Interpersonal trust is linked to therapeutic factors of patient care, including adherence to treatment, continuity with a provider, perceived effectiveness of care, and clinical outcomes. ...
Fluid and gyrokinetic turbulence in open field-line, helical plasmas

Two-fluid Braginskii codes have simulated open-field line turbulence for over a decade, and only recently, it has become possible to study these systems with continuum gyrokinetic codes. This work presents a first-of-its-kind comparison between fluid and (long-wavelength) gyrokinetic models in open field-lines, using the GDB and Gkeyll codes to simulate interchange turbulence in the Helimak device at the University of Texas [T. N. Bernard et al., Phys. Plasmas 26, 042301 (2019)]. Partial agreement is attained in a number of diagnostic channels when the GDB sources and sheath boundary conditions (BCs) are selected carefully, especially the heat-flux BCs that can drastically alter the temperature. The radial profile of the fluctuation levels is qualitatively similar and quantitatively comparable on the low-field side, although statistics such as moments of the probability density function and the high-frequency spectrum show greater differences. This comparison indicates areas for future improvement in both simulations, such as sheath BCs, and improvements in GDB like particle conservation and spatially varying thermal conductivity, in order to achieve better fluid-gyrokinetic agreement and increase fidelity when simulating experiments.
Case Report: Acute Abdominal Pain as Presentation of Pneumonia and Acute Pancreatitis in a Pediatric Patient With COVID-19

Abdominal pain, nausea, and vomiting are known gastrointestinal symptoms of symptomatic SARS-CoV-2 infection (COVID-19 disease) in pediatric patients.(1) There is little literature regarding pancreatitis in COVID-19. We describe a 16-year-old male diagnosed with acute pancreatitis in the setting of a SARS-COV-2 infection and associated fluid balance considerations.
The Pharmacy Student Population: Applications Received 2019-20, Degrees Conferred 2019-20, Fall 2020 Enrollments.

This report presents data that describe the 2019-20 pharmacy application pool, degrees conferred in 2019-20, and fall 2020 pharmacy program enrollments. As of fall 2020 there were 141 colleges and schools of pharmacy with accredited (full, candidate, and precandidate status) professional degree
Some Historical Remarks

In the next three chapters I solve completely a problem of Katai; and improve and generalize a theorem of Wirsing. These problems involve the characterization of additive arithmetic functions in terms of their differences.
Change(d) Agents: New Teachers of Color in Urban Schools. Betty Achinstein and Rodney Ogawa

Change(d) Agents: New Teachers of Color in Urban Schools constitutes Betty Achinstein and Rodney Ogawa's attempt at providing solutions to various pressing issues faced by novice minority teachers ...
Performance of Multicore Systems on Parallel Data Clustering with Deterministic Annealing

We present a performance analysis of a scalable parallel data clustering algorithm with deterministic annealing for multicore systems that compares MPI and a new C# messaging runtime library CCR (Concurrency and Coordination Runtime) with Windows and Linux and using both threads and processes. We investigate effects of memory bandwidth and fluctuations of run times of loosely synchronized threads. We give results on message latency and bandwidth for two processor multicore systems based on AMD and Intel architectures with a total of four and eight cores. We compare our C# results with C using MPICH2 and Nemesis and Java with both mpiJava and MPJ Express. We show initial speedup results from Geographical Information Systems and Cheminformatics clustering problems. We abstract the key features of the algorithm and multicore systems that lead to the observed scalable parallel performance.
Are we there yet? Genomic profiling and mechanism in cancer research

The advent of the human genome sequence and genomic profiling technologies has impacted all of biomedical research. The effect has been particularly great on cancer research because cancer is a disease uniformly characterized by disturbed genome function. Studies which take a whole genome view of cancer are transforming the classification of tumors, enhancing understanding of tumorigenesis and promising to affect patient care. However, the development of large sets of genomic data has challenged cancer biologists who as a rule have never encountered data on this scale. Implementation of conventional statistical techniques has brought a level of order to the biologist's desktop, but significant problems remain to be solved. The challenge remains to extract the maximum useful information from genomic data. This requires both new algorithmic approaches which can accommodate the complexity of the underlying rules of genome function and effective strategies for linking different types of genomic data to each other and to external sources of gene and genome annotation. Progress in this arena will be necessary to fully realize the potential of genomics to impact on our ability to intervene in the clinical arena. Of particular importance will be approaches which help identify critical genes and pathways which are essential to tumor growth and survival. Examples will be presented which illustrate the boundaries of conventional analyses based on studies of tumor profiling at the expression and gene copy number level as well as experimental models designed to explore the function of specific pathways.
Purification and properties of D-serine dehydrase from Escherichia coli.

Abstract A procedure is described for obtaining crystalline d-serine dehydrase from a mutant of Escherichia coli which produces this enzyme constitutively. The enzyme appears pure by ultracentrifugal and electrophoretic criteria. In sucrose gradients, serine dehydrase sediments to the same position as horseradish peroxidase, indicating a molecular weight of about 40,000. This corresponds closely to its combining weight of 42,800 per pyridoxal phosphate. Its absorption maximum at 410 mµ due to bound pyridoxal phosphate is not materially changed by interaction with substrate or by variation in pH between 6.0 and 9.0. d-Serine and d-threonine are the only substrates found; O-methylserine is a potent competitive inhibitor. In the presence of suitable protective agents, the enzyme can be resolved completely by dialysis against d- or l-cysteine, and reactivated by addition of pyridoxal phosphate. Tris buffer inactivates the enzyme; this inactivation is prevented by the presence of sufficient K+ or NH4+, and less effectively by Na+ or pyridoxal phosphate.
Arachidonic acid and endothelin potentiate Ca2+ transients in rat cardiac myocytes via inhibition of distinct K+ channels.

The release of arachidonic acid by phospholipases in response to cell surface receptor activation may be an important step in the initiation of inotropic events in cardiac muscle. Endothelin has been shown to activate phospholipase A2 and release arachidonic acid in isolated rat hearts. Endothelin also has a positive inotropic effect in cardiac muscle, suggesting that endothelin increases Ca2+ influx or the amount of Ca2+ released from the sarcoplasmic reticulum. We used suspensions of adult rat ventricular myocytes loaded with fura-2/AM to compare the effects of arachidonic acid and endothelin on Ca2+ transients evoked by extracellular ATP. We showed recently (Damron, D.S., and Bond, M. (1993) Circ. Res. 72, 376-386) that pretreatment of cardiac myocytes with arachidonic acid significantly potentiated the amplitude of the ATP-triggered Ca2+ transient. We now report that endothelin also enhances the ATP-triggered Ca2+ transient and that the effect of the combination of maximal doses of endothelin and arachidonic acid is additive. Neither endothelin nor arachidonic acid was found to affect the size of the sarcoplasmic reticulum Ca2+ store. The potentiating effects of both arachidonic acid and endothelin were sensitive to inhibitors of protein kinase C. Endothelin was also found to stimulate phospholipase C but not phospholipase A2. Application of arachidonic acid to individual cardiac muscle cells resulted in inhibition of the transient outward K+ current, whereas application of endothelin inhibited the delayed rectifier current. These effects of arachidonic acid and endothelin were additive, and both effects could be blocked by the protein kinase C inhibitor, staurosporine. Similarly, staurosporine inhibited endothelin-induced increases in isometric contractions in ventricular papillary muscle. We conclude that arachidonic acid and endothelin may be involved in the modulation of inotropic activity in cardiac muscle by means of protein kinase C-dependent inhibition of two distinct K+ channels. This would result in a prolongation of action potential duration and thus an increase in Ca2+ influx across the sarcolemma.
Particle Correlations in Z and WW Events

Important information about the dynamics of hadron production can be obtained by the study of particle correlations. More than 16 million hadronic Z0 decays and several thousand W+W- events have been recorded from the four LEP collaborations between 1989 and 2000. Recently, in Z0 decays, new results of Bose-Einstein correlations in pairs of pions and Fermi-Dirac correlations for antiproton pairs were reported. In fully-hadronic W+W- decays particle correlations were used to study whether the two W bosons decay independently.
Investing in Civic and Political Pluralism

David Meens critiques federally funded service learning programs on the grounds that if these are designed to be a form of citizenship education, then they present far too narrow a version of citizenship — one that is all service and not at all political. Meens argues that the political origins of these programs help explain why the view of citizenship is defined so narrowly. I am not going to address that issue here. Instead, I sort out some of the concepts in the argument and then address Meens’ critique of the model of citizenship promoted through service learning programs directed at college-bound and college-attending young adults.
Combined melanocytic and sweat gland neoplasm: cell subsets harbor an identical HRAS mutation in phacomatosis pigmentokeratotica

Phacomatosis pigmentokeratotica (PPK) is characterized by the co-existence of epidermal nevi and large segmental speckled lentiginous nevi of the papulosa type. PPK, previously explained as 'twin spot' mosaicism due to the postzygotic crossing-over of two homozygous recessive mutations, has recently been shown to derive from one postzygotic activating RAS mutation. Epidermal nevi, including those in PPK, are known to give rise to neoplasms such as trichoblastoma and basal cell carcinoma. Within speckled lentiginous nevi, Spitz nevi and melanoma have been well documented. We report a case of PPK with a combined melanocytic and adnexal neoplasm presenting where the nevi conjoined. Using next-generation sequencing techniques, we were able to identify the same HRAS G13R mutation within both components of the tumor, and to show the absence of additional mutated modifier genes in a panel of 300 cancer-related genes. Given the genetic findings in this rare tumor-type, we suggest that this case may be used as a model for understanding the development of biphenotypic neoplasia or intratumoral heterogeneity in some cases.
Psychology and decision making: modelling health behavior with multiattribute utility theory

The success of much of dental practice is linked to patient behavior. Understanding the issues that influence patients9 decisions when they choose to not follow preventive or therapeutic dental recommendations is instrumental to improving adherence, and ultimately, to improving dental health outcomes. Multiattribute Utility Theory (MAU) provides a methodology for systematically exploring these issues. It is based on a well-established body of knowledge in the psychological literature, and currently represents a state-of-the-art model for predicting behavior and delineating potentially modifiable behavioral determinants. Two examples are presented to illustrate how MAU can be used in clinical settings. In the first example, MAU is used to identify key reasons why nearly 70 percent high-risk patients did not obtain flu shots, a behavioral problem comparable to many confronted in dentistry. MAU correctly predicted the vaccination behavior of 82 percent of patients, and an intervention based on MAU findings nearly doubled vaccination rates. The second example used MAU to identify physician behaviors that influenced patients9 satisfaction with an ambulatory care visit. MAU findings from this study identified specific behaviors in a provider9s style that if modified may improve patient satisfaction. These MAU applications also emphasize the importance of soliciting the patient9s perspective in clinical interactions since some of the most important determinants of patient behavior are not represented in traditional clinical decision models.
Some inhibitory effects of (--)-emetine on growth of Ehrlich ascites carcinoma.

(−)-Emetine has little or no effect on O2 consumption of Ehrlich ascites-cell suspensions or on the viability of transplanted Ehrlich ascites-tumour cells exposed to, or incubated with, the drug in vitro before inoculation into new-host mice. (−)-Emetine administered as a single injection to mice bearing Ehrlich ascites-tumour cells slows the growth rate of the tumour. The subcutaneous or intraperitoneal injection of the drug depresses protein and DNA synthesis of the tumour cells in vivo in a reversible manner. Mice bearing ascitic sarcoma 180 or Ehrlich ascites-tumour cells when given a course of treatment with (−)-emetine or (−)-O-methyltubulosine have a substantially lower tumour load than untreated controls and correspondingly longer survival times.
Multidimensional Scaling and the Organizational Sciences

Multidimensional Scaling (MDS) is proposed as a viable research methodology for use by organizational scientists. A brief description of the method is presented, and past uses of the methodology are discussed. Possible uses for MDS are described in the areas of construct development and schema recovery. The process is viewed as an alternative and complimentary methodology to traditional organization research approaches.
Effect of pulley excision on flexor tendon biomechanics.

Flexor tendon function following excision of various portions of the fibro-osseous pulley system was measured biomechanically using a tensile testing machine. The biomechanical parameters measured were tendon excursion (the excursion of the tendon required to fully flex the digit) and work of flexion (the area under the force-excursion curve, representing all the forces that resist tendon flexion). In this experiment, work of flexion included the forces necessary to accomplish full digital flexion against a 15-g counterweight, as well as the frictional forces that resist tendon gliding. The results indicate that the work of flexion was affected to a greater degree by pulley loss than was tendon excursion, suggesting that it is a more sensitive measurement of tendon function. A2 was found to be the single most important pulley for flexor tendon function, followed by A4. However, both A2 and A4 had to be present if near-normal hand function was to be achieved; sacrificing the A1 pulley was not associated with a significant loss of flexion. The “pulley effect” of the skin and soft tissue as a supplement to the fibro-osseous pulleys in reducing tendon bow-stringing was also noted. Although the parameters of tendon excursion and work of flexion were used in this study to determine the effect of pulley loss on tendon function, they can also be used to evaluate other flexor tendon studies, such as pulley reconstruction.
The fuzzy integral

Abstract In this paper we define the fuzzy integral of a positive, measurable function, with respect to a fuzzy measure. We show that the monotone convergence theorem and Fatou's lemma are still true in this new setting. We study some of the properties of this integral, and show that it coincides with another fuzzy integral defined in the literature. Our main result is a convergence theorem, that is in a way stronger than the Lebesgue-dominated convergence theorem. This holds when the fuzzy measure is also assumed to be subadditive.
Pancreatic islet cell damage in mice produced by coxsackie B 1 and encephalomyocarditis viruses.

In den β-Zellen der Langerhans'schen Inseln des Pankreas wurden Viruskristalle von mit Encephalomyocarditis-Virus oder Coxsackie-B10Virus infizierten Mausen gefunden. Die Inselzellen zeigten sowohl leichte als auch schwere Schadigung.
On mapping algorithms to linear and fault-tolerant systolic arrays

A simple mapping technique is developed to design systolic arrays with limited I/O capability. The technique is used to improve systolic algorithms for some matrix computations on linearly connected arrays of PEs (processor elements) with constant I/O bandwidth. The important features of these designs are modularity with constant hardware in each PE, few control lines, simple data-input/output format, and improved delay time. This technique is extended to design an optimal n square root n-time systolic algorithm for n*n matrix multiplication with O( square root n) I/O bandwidth requirement on a fault-tolerant VLSI model. In this model, the propagation delay is assumed to be proportional to wire length. Fault reconfiguration is achieved by using buffers to bypass faulty PEs, which does not affect the clock rate of the system. The unidirectional flow of control and data assures correctness of the algorithm in the presence of faulty PEs. The design can be implemented on reconfigurable fault-tolerant VLSI arrays using the Diogenes methodology. The present designs are compared to those in the literature and are shown to be superior with respect to I/O format, control, and delay from input to output. >
Host-determined t-cell fine specificity for self- -h-2 in radiation bone marrow chimeras of standard c57bl/6 (h-2b), mutant hz1(h-2ba), and f1 mice.

Reciprocal radiation bone-marrow chimeras were produced between the standard C57BL/6 (=B6) and the mutant B6.C-H-2ba (=Hz1) strain. When infected with vaccinia virus, these chimeras, as well as an (Hz1 × B6)=→ Hz1 chimera, produced cytotoxic cells that killed vaccinia-infected H-2KkH-2Db target cells but failed to kill virus-infected H-2KbH-2Dd cells. Virus-infected (Hz1 × B6)F1 → B6 chimeras, however, killed both types of target. These experiments demonstrate strict T-cell specificity capable of differentiating between two molecules that apparently differ by a single amino acid substitution.
SUBJECTIVE EXPECTED UTILITY THEORY REVISITED: A REDUCTIO AD ABSURDUM PARADOX

A paradox is posed and analyzed in which people reverse their preferences for information on probabilities versus prizes once the range of the unknown probabilities is sufficiently narrowed. This reversal is shown to be incompatible with both objective expected utility (EU) as well as subjective versions in which the same probability transformation applies to all random variables. Experimental data are presented showing that the reversals occur with small, medium and large payoffs. The present paradox is compared with those of Allais and Ellsberg, and found to differ in substantive ways. It raises further questions about the normative status of expected utility theory, especially its treatment of probability and value. The paradox specifically calls into question EU's substitution and compound probability axioms.
Epidemiology of Infection and Colonization With Vancomycin-Resistant Enterococci and Frequency of Cocolonization With Methicillin-Resistant Staphylococcus aureus in Children

We report the descriptive and molecular epidemiology of vancomycin-resistant enterococci (VRE) infection and colonization and cocolonization with methicillin-resistant Staphylococcus aureus (MRSA) in children. Interunit and intraunit spread of VRE was detected, and 8 cases of VRE-MRSA cocolonization were identified. Seven of these cases were identified only via active surveillance, because clinical evidence of VRE colonization was absent.
A preliminary study on the feasibility of friction stir back extrusion

The feasibility of producing fine-grained tubes via the novel concept of friction stir back extrusion was investigated. A rotating tool is plunged into aluminium round bar specimens at a selected feed rate, forcing the processed material radially outwards and thus forming tubes. Preliminary results show that the process is capable of producing structurally-sound, void-free tubes; optical microscopy clearly shows the presence of a stir zone, and grain size measurements indicate significant refinement in the microstructure of the starting material.