cssi/SciSciGPT-SciSciNet huggingface dataset:
Site-directed mutagenesis of a regulatory site of Escherichia coli ADP-glucose pyrophosphorylase: the role of residue 336 in allosteric behavior.

Site-directed mutagenesis was used to probe the role of glycine residue 336 in the regulatory properties of Escherichia coli ADP-glucose pyrophosphorylase. This residue was previously found to be changed from glycine to aspartate in the gene of an Escherichia coli mutant strain. The mutant enzyme had altered kinetic properties, including higher activity in the absence of the activator fructose 1,6-bisphosphate (FBP), higher apparent affinity for FBP and substrates, and lower apparent affinity for the inhibitor AMP. The observed changes in activity were caused by this single mutation, because the aspartate mutant was prepared from the wild-type gene. The kinetic properties of the site-directed mutant are identical to those of the enzyme from the mutant strain. A series of mutants was prepared to explore the effects of charge, size, shape, and hydrophobicity of the amino acid at residue 336 on the enzyme regulatory properties. All of the mutants, except for the lysine and arginine enzymes, were expressed and purified for kinetic analysis. The glycine-336 residue is able to tolerate diverse substitutions without compromise of catalytic activity. A range of allosteric changes was observed, with the most dramatic effects seen with the highly active aspartate enzyme and the low-activity G336Q mutant, which exhibited lower apparent affinities for activator and substrates and higher apparent affinity for inhibitor. The altered allosteric properties of the G336D mutant enzyme were almost completely abolished by substitution of asparagine. Thus, the aspartate negative charge is essential for the altered binding of effectors.
Pretreatment with transdermal nicotine enhances some of ethanol's acute effects in men

Nicotine and alcohol are often consumed together and smokers are more likely than non-smokers to drink alcohol. In spite of the high prevalence of the combined use of alcohol and nicotine, only a few laboratory studies have examined the effects of this drug combination in humans. The present study was conducted to further investigate the nature of nicotine/alcohol interactions by examining whether nicotine pretreatment via a transdermal patch (placebo or 21 mg) alters the subjective and physiologic effects of acute ethanol (0.4 and 0.7 g/kg) administration. Twelve male smokers who drank alcohol on an occasional basis provided informed consent to participate in the study. Subjective reports of feeling drunk, feeling ethanol's effects and ethanol-induced euphoria were increased by nicotine pretreatment. In addition, reports of desire to smoke a tobacco cigarette were significantly elevated after ethanol administration and were most pronounced during the active nicotine conditions. Heart rate was elevated by nicotine and ethanol-induced increases in heart rate were enhanced by nicotine pretreatment. The time to peak ethanol concentration was faster in the nicotine-patch condition and this paralleled the more rapid detection of ethanol effects after drinking the low-dose beverage. These findings suggest that nicotine enhances some of the positive subjective effects of acute ethanol and may help explain the high prevalence of the combined use of these two drugs.
A Theory of Memory Retrieval.

A theory of memory retrieval is developed and is shown to apply over a range of experimental paradigms. Access to memory traces is viewed in terms of a resonance metaphor. The probe item evokes the search set on the basis of probe-memory item relatedness, just as a ringing tuning fork evokes sympathetic vibrations in other tuning forks. Evidence is accumulated in parallel from each probe-memory item comparison, and each comparison is modeled by a continuous random walk process. In item recognition, the decision process is self-terminating on matching comparisons and exhaustive on nonmatching comparisons. The mathematical model produces predictions about accuracy, mean reaction time, error latency, and reaction time distributions that are in good accord with experimental data. The theory is applied to four item recognition paradigms (Sternberg, prememorized list, study-test, and continuous) and to speed-accuracy paradigms; results are found to provide a basis for comparison of these paradigms. It is noted that neural network models can be interfaced to the retrieval theory with little difficulty and that semantic memory models may benefit from such a retrieval scheme.
Effect of the duration and direction of storm movement on infiltrating planar flow with full areal coverage

Using kinematic wave equations, analytical solutions are derived for flow due to a storm moving up or down an infiltrating plane and covering it completely. The storm duration is assumed in two ways. First, the plane is covered everywhere for the same duration by the storm. Second, the plane is covered in a linearly decreasing manner from the beginning of its coverage of the plane to the other end of the plane. By comparing the flow due to this storm with that due to a stationary storm of the same duration, the influence of storm duration, direction and velocity on flow hydrograph is investigated. It is found that storm movement has a pronounced effect on runoff hydrograph. Copyright © 2002 John Wiley & Sons, Ltd.
Effects of instant messaging on the management of multiple project trajectories

We present a study of the effects of instant messaging (IM) on individuals' management of work across multiple collaborative projects. Groups of four participants completed four web design tasks. Each participant worked on two tasks, each task with a different partner who was either co-located or remote, connected via IM. In one condition, each participant had one co-located and one remote partner. In a second condition, both partners were remote. We examined communication, division of labor, and task performance as a function of condition. The results indicated that nearly all participants divided their time unequally between projects, but less unequally in the remote/remote condition. In the co-located/remote condition, participants favored the task with the co-located partner. The results show that the effects of IM differ depending on people's multiple tasks are distributed across space. We propose a new IM interface that promotes awareness of multiple collaborators on multiple tasks.
Induction of a Selective and Persistent Extravasation of Neutrophils into the Peritoneal Cavity by Tryptase Mouse Mast Cell Protease 6

Recombinant mouse mast cell protease 6 (mMCP-6) was generated to study the role of this tryptase in inflammatory reactions. Seven to forty-eight hours after the i.p. injection of recombinant mMCP-6 into BALB/c, mast cell-deficient WCB6F 1 - Sl/Sl d , C5-deficient, or mMCP-5-null mice, the number of neutrophils in the peritoneal cavity of each animal increased significantly by >50-fold. The failure of the closely related recombinant tryptase mMCP-7 to induce a comparable peritonitis indicates that the substrate specificities of the two tryptases are very different. Unlike most forms of acute inflammation, the mMCP-6-mediated peritonitis was relatively long lasting and neutrophil specific. Mouse MCP-6 did not induce neutrophil chemotaxis directly in an in vitro assay, but did promote chemotaxis of the leukocyte in the presence of endothelial cells. Mouse MCP-6 did not induce cultured human endothelial cells to express TNF-α, RANTES, IL-1α, or IL-6. However, the tryptase induced endothelial cells to express large amounts of IL-8 continually over a 40-h period. Neither enzymatically active mMCP-7 nor enzymatically inactive pro-mMCP-6 was able to induce endothelial cells to increase their expression of IL-8. Although the mechanism by which mMCP-6 induces neutrophil accumulation in tissues remains to be determined, the finding that mMCP-6 induces cultured human endothelial cells to selectively release large amounts of IL-8 raises the possibility that this tryptase regulates the steady state levels of neutrophil-specific chemokines in vivo during mast cell-mediated inflammatory events.
Size dependence of two photon absorption in CdSe nanoparticles

The two photon absorption coefficient at 1:55 eV of CdSe nanoparticles was determined from the induced transient bleaching of their first exciton transitions by a femtosecond white light probe. Dependence on particle size was investigated.
Real-time automated thickness measurement of the in vivo human tympanic membrane using optical coherence tomography

Background: Otitis media (OM), an infection in the middle ear, is extremely common in the pediatric population. Current gold-standard methods for diagnosis include otoscopy for visualizing the surface features of the tympanic membrane (TM) and making qualitative assessments to determine middle ear content. OM typically presents as an acute infection, but can progress to chronic OM, and after numerous infections and antibiotic treatments over the course of many months, this disease is often treated by surgically inserting small tubes in the TM to relieve pressure, enable drainage, and provide aeration to the middle ear. Diagnosis and monitoring of OM is critical for successful management, but remains largely qualitative. Methods: We have developed an optical coherence tomography (OCT) system for high-resolution, depth-resolved, cross-sectional imaging of the TM and middle ear content, and for the quantitative assessment of in vivo TM thickness including the presence or absence of a middle ear biofilm. A novel algorithm was developed and demonstrated for automatic, real-time, and accurate measurement of TM thickness to aid in the diagnosis and monitoring of OM and other middle ear conditions. The segmentation algorithm applies a Hough transform to the OCT image data to determine the boundaries of the TM to calculate thickness. Results: The use of OCT and this segmentation algorithm is demonstrated first on layered phantoms and then during real-time acquisition of in vivo OCT from humans. For the layered phantoms, measured thicknesses varied by approximately 5 µm over time in the presence of large axial and rotational motion. In vivo data also demonstrated differences in thicknesses both spatially on a single TM, and across normal, acute, and chronic OM cases. Conclusions: Real-time segmentation and thickness measurements of image data from both healthy subjects and those with acute and chronic OM demonstrate the use of OCT and this algorithm as a robust, quantitative, and accurate method for use during real-time in vivo human imaging.
Development of an in situ underwater particle image velocimetry (UWPIV) system

A low-cost self-contained underwater particle image velocimetry (UWPIV) system has been developed to measure small-scale turbulent flow structures in situ. The UWPIV employs a compact continuous-wave laser and an optical scanner to deliver a light sheet that illuminates naturally occurring particles. Particle images are taken by a CCD camera along with an ultra-compact PC. The nontethered and compact design can be fit in two small underwater housings with all components powered by batteries: an ideal design for a variety of in situ deployments. The system has been field-tested in the coastal zone of Lake Michigan. Turbulent flow structures of the wave-current bottom boundary layer are measured right above the nearshore lakebed, which is densely covered by quagga mussels (Dreissena bugensis). Vertical profiles of mean velocity, Reynolds stresses, dissipation rate of the turbulent kinetic energy, turbulent viscosity, plankton particle concentration, and the turbulent flux of particles are presented and discussed.
Genomic Instability, as Measured by Microsatellite Alterations, Is Not Associated with Liver Tumor Development in the Genetically Susceptible B6C3F1 Mouse

Certain human heritable forms of colon cancer have characteristically high frequencies of microsatellite alterations. These microsatellite changes are markers of genomic instability and the direct consequence of mutations in genes involved with DNA mismatch repair processes, which are in part responsible for maintaining the sequence integrity of the genome. Given that the B6C3F1 mouse is genetically predisposed to develop liver tumors we were interested in determining whether tumors derived in this strain of mouse may contain alterations in microsatellite sequences. The analysis of 48 tumors at 24 different microsatellite loci revealed that microsatellite alterations were detected in 12 of 48 tumors (25%). Although this frequency is relatively high, 11 of the 12 tumors exhibited only a single alteration and in 10 of those tumors this change was at the same microsatellite locus. Microsatellite alterations were also detected in the DNA isolated from 6 of 22 (27%) normal liver tissues with 4 of the 6 occurring at the same locus where the majority of changes were observed in the tumors. Based on these results, we conclude that the microsatellite alterations present in the mouse liver tumor tissue are most likely the result of spontaneous mutational events. Consequently, the genomic instability operational in a particular type of hereditary human colon cancer does not appear to be operational in the genetically predisposed B6C3F1 mouse liver. In addition, we demonstrated that the activation of the H-ras gene, which causes some forms of genetic instability in vitro, does not contribute to genetic instability within liver tumors as measured by microsatellite alterations.
Comparative evaluation of memory models for chip multiprocessors

There are two competing models for the on-chip memory in Chip Multiprocessor (CMP) systems: hardware-managed coherent caches and software-managed streaming memory. This paper performs a direct comparison of the two models under the same set of assumptions about technology, area, and computational capabilities. The goal is to quantify how and when they differ in terms of performance, energy consumption, bandwidth requirements, and latency tolerance for general-purpose CMPs. We demonstrate that for data-parallel applications on systems with up to 16 cores, the cache-based and streaming models perform and scale equally well. For certain applications with little data reuse, streaming scales better due to better bandwidth use and macroscopic software prefetching. However, the introduction of techniques such as hardware prefetching and nonallocating stores to the cache-based model eliminates the streaming advantage. Overall, our results indicate that there is not sufficient advantage in building streaming memory systems where all on-chip memory structures are explicitly managed. On the other hand, we show that streaming at the programming model level is particularly beneficial, even with the cache-based model, as it enhances locality and creates opportunities for bandwidth optimizations. Moreover, we observe that stream programming is actually easier with the cache-based model because the hardware guarantees correct, best-effort execution even when the programmer cannot fully regularize an application's code.
Validity and reliability of the chronic heart failure questionnaire mastery subscale in patients with defibrillators.

Reliable, valid measures are needed to assess one’s sense of mastery, which has the potential for decreasing anxiety and depressive symptoms among patients with implantable cardioverter-defibrillators (ICDs). This study evaluates the reliability and validity of a measure of mastery, the Chronic Heart Failure Questionnaire (CHQ) mastery subscale. One hundred twenty-two (75% men, mean age 65 years) and 100 patients complete baseline and 12-month face-to-face interviews, respectively. The CHQ mastery subscale is found to have internal consistency reliability (Cronbach’s alphas = .79, .84), and its validity is supported. Factor analysis yields a single robust factor. Differences in the CHQ mastery subscale scores by the New York Heart Association (NYHA) classes are found: Patients with NYHA Class III or IV have lower mastery than those with Class I or II. Baseline younger age and less frequent ICD shocks and lower mastery are significant predictors of respectively 12-month anxiety (R 2 = .37) and depressive s...
False Positives in Urine Monitoring of Substance Abusers

The authors provide two examples of formerly substance-abusing physicians who had false-positive urine tests while being monitored for addictive substances. Urine tests are not infallible and can return both false-positive and false-negative results that must be addressed. The role of urine monitoring in assessing the recovery of patients from substance abuse is discussed with emphasis on the need to include multiple sources of clinical input in assessing the patient.
Using checklists and collections data to investigate plant diversity: II. An analysis of five florulas from northeastern South America

Abstract Five plant checklists from areas on and adjacent to the Guiana Shield were analyzed and used to test hypotheses of the salient properties of the flora of northeastern South America. Newly available checklists of Iwokrama, Mabura Hill, and Kaieteur Falls (all three in Guyana), Central French Guiana, and Reserva Ducke near Manaus, Brazil were compiled and their nomenclatural synonymies standardized. Data from checklists provide an attractive alternative to transect or plot data because they are based on rigorously determined plants of all habit types rather than the sterile vouchers of tree species often used in plot or transect studies. Descriptive data were compiled from the checklists regarding diversity, overlap, and endemism. Ranking of diversity at the family level was subjected to Kendall's coefficient of concordance of ranks test and Spearman rank correlation coefficients to evaluate similarities among the five sites. A UPGMA dendrogram was created from data for the presence or absence of s...
Where Are They? A Multilens Examination of the Distribution of Full-Time Faculty by Institutional Type, Race/Ethnicity, Gender, and Citizenship.

This introduction chapter presents descriptive statistics on the postsecondary faculty population in the United States and highlights the progressing diversity and growing number of minority, women, and international faculty
Heavy vehicle fuel economy improvement using ultracapacitor power assist and preview-based MPC energy management

A heavy hybrid vehicle is considered in which an electric motor and ultracapacitor energy storage are used in a parallel hybrid configuration as a power assist to improve fuel economy. The ultracapacitor's high power capabilities make it a good choice for this application. The optimal control technique of Dynamic Programming (DP) is applied to obtain the “best possible” fuel economy for the vehicle over the driving cycle under pointwise-in-time hard system constraints. Attainable fuel economy improvements are illustrated using a real-time implementable Model Predictive Control (MPC) method using a simple model for predicting future torque demands. The incorporation of simulated telematic future information is also investigated to further improve the the fuel economy of the MPC method close to the DP-calculated maximum.
Energy distribution in a scatterplate interferometer

In this paper, a Fourier-optics approach to scatterplate interferometry is introduced. In particular, it is used to explain how energy is conserved for both “phase”- and “density”-type scatterplates.
The Relationship Between Learning Disability and Juvenile Delinquency Current State of Knowledge

Is there a link between learning disabilities and juvenile delinquency? If so, what is the nature of that link? Can it be broken by a program of remediation? This article describes the background, research, and results of a multiyear project, the Learning Disability-Juvenile Delinquency Project, designed to address these questions. The results of cross-sectional and longitudinal studies of samples of adolescent males from public schools, juvenile courts, and correctional facilities confirm the school failure theory, the susceptibility theory, and the differential treatment theory—theories positing a causal relationship between learning disability and juvenile delinquency. Adolescents with learning disabilities had significantly higher rates of general delinquent behavior; they engaged in more violence, substance abuse, and school disruption than non-learning-disabled adolescents. The likelihood of arrest and adjudication was also substantially higher for adolescents handicapped by learning disabilities. A...
Merging interface schemas on the deep Web via clustering aggregation

We consider the problem of integrating a large number of interface schemas over the deep Web, The scale of the problem and the diversity of the sources present serious challenges to the conventional manual or rule-based approaches to schema integration. To address these challenges, we propose a novel formulation of schema integration as an optimization problem, with the objective of maximally satisfying the constraints given by individual schemas. Since the optimization problem can be shown to be NP-complete, we develop a novel approximation algorithm LMax, which builds the unified schema via recursive applications of clustering aggregation. We further extend LMax to handle the irregularities frequently occurring among the interface schemas. Extensive evaluation on real-world data sets shows the effectiveness of our approach.
Comprehensive Model Simulation of Thermal Tides in the Martian Atmosphere

Abstract This paper discusses the thermotidal oscillations in simulations performed with a newly developed comprehensive general circulation model of the Martian atmosphere. With reasonable assumptions about the effective thermal inertia of the planetary surface and about the distribution of radiatively active atmospheric aerosol, the model produces both realistic zonal-mean temperature distributions and a diurnal surface pressure oscillation of at least roughly realistic amplitude. With any reasonable aerosol distribution, the simulated diurnal pressure oscillation has a very strong zonal variation, in particular a very pronounced zonal wavenumber-2 modulation. This results from a combination of the prominent wave-2 component in the important boundary forcings (topography and surface thermal inertia) and from the fact that the eastward-propagating zonal wave-1 Kelvin normal mode has a period near 1 sol (a Martian mean solar day of 88 775 s). The importance of global resonance is explicitly demonstrated w...
Comments on the Climax and Wolf Creek Pass Cloud Seeding Experiments

Abstract The physical hypotheses for the cloud seeding experiments carried out by Colorado State University in the Colorado Rockies (Climax I and II and Wolf Creek Pass) in the 1960's are critically examined. Airborne measurements over the Rockies have shown that the concentrations of ice particles in the natural clouds are often much greater than originally assumed; consequently, the conditions under which it might be possible to increase precipitation by artificial seeding are probably much more limited than previously supposed. There appears to be no firm evidence to support the contention that 500 mb temperatures are a good measure of cloud-top temperatures over the Rockies. Finally, examination of a more extensive data set than previously used fails to substantiate the claim that precipitation over the Rockies decreases as 500 mb temperatures increase above certain values.
Does Women’s Land Ownership Promote Their Empowerment? Empirical Evidence from Nepal

Land rights equity is seen as an important tool for increasing empowerment and economic welfare for women in developing countries. Accordingly, the objective of this paper is to empirically examine the role of women’s land ownership, either alone or jointly, as a means of improving their intra-household bargaining power in the areas of own healthcare, major household purchases, and visiting family or relatives. Using the 2001 and 2011 Nepal Demographic and Health Surveys and relevant econometric techniques, we find that land ownership has a positive and significant impact on women’s empowerment. In particular, we find two important patterns of results. First, accounting for the endogeneity of land ownership with inverse probability weighting, coarsened exact matching and instrumental variable methods makes its impact on empowerment higher. Previous research in this area had largely ignored the potential endogeneity of land ownership. Second, the impact is generally stronger in 2011 than in 2001. As evidenced in a number of empirical studies, the increase in women’s bargaining power can in turn translate into a redirection of resources toward women’s preferences, including higher investment in human capital of the household such as education, health, and nutrition. Therefore, our study indicates that in places where agriculture is the main source of economy for women, policies enhancing land rights equity have the potential to increase women’s empowerment and associated beneficial welfare effects.
Photocatalytic Oxidation of Five Contaminants of Emerging Concern by UV/TiO2: Identification of Intermediates and Degradation Pathways

Abstract The simultaneous TiO2/UV photocatalytic degradation of 1,4-dioxane, n-nitrosodimethylamine (NDMA), tris-2-chloroethyl phosphate (TCEP), gemfibrozil (GEM), and 17β-estradiol (E2) in water at pH 5.0 and 1.5 g/L TiO2 using a 1-L slurry photoreactor was investigated. Intermediates originating from degradation of individual contaminants and interaction between them were evaluated and possible reaction pathways were suggested. Gas chromatography/mass spectroscopy analysis was used for identification of these intermediates. Results obtained showed that the compounds identified were mostly derived from 1,4 xylenol, a moiety from gemfibrozil. Isomerization and alkyl shift mechanisms were found to be responsible for formation of intermediates. Nitrogen compounds derived from NDMA degradation were reactive with other fragments and generated several other compounds such as pyridines, secondary amines, carbamate derivatives, and diazoles. Interaction between 1,4-dioxane and TCEP by-products was limited to for...
Curtailing the Judicial Certification of Expert Witnesses

In his Article, Professor Kirgis argues that the familiar practice of judicial certification of expert witnesses lacks a foundation in law and common-sense. Professor Kirgis complements his argument with a discussion ofseveralpractical considerations that arise when a litigator elects to challenge the judicial qualification of an opponent's expert witness.
Imagined Interaction Frequency and the Five-Factor Model of Personality

Imagined interactions (IIs) are a form of daydream in which an individual imagines a communication interaction with one or more others. One of the most important attributes of II is frequency, a trait variable that measures how often people have imagined interactions. Individual differences in personality have been shown to predict II frequency. This cross-sectional study of N = 104 undergraduates examines the effects of personality, operationalized with the five-factor model, on II frequency. Results indicate that the model overall does predict II frequency. Individually, openness to experience, neuroticism, and conscientiousness are significant predictors of II frequency, but extroversion and agreeableness seem to have little to no effect.
Dispersed Fluorescence Spectroscopy of S0 Formyl Fluoride Vibrational States

Dispersed fluorescence (DF) spectroscopy was used to record a 22 500 cm-1 spectrum of the vibrational energy levels of formyl fluoride (HFCO) and thereby determine harmonic frequencies and anharmonic constants for the S0 potential energy surface. Sample molecules were cooled in a supersonic expansion and excited to low J, Ka = 0 rotational states in the 62 vibrational level of S1 HFCO, and the resulting fluorescence was dispersed from 255 to 600 nm. Long progressions in the CO stretch (υ2 = 0−6) and out-of-plane bend (υ6 = 0−23) and shorter progressions in the CF stretch (υ4 = 0−2) and FCO bend (υ5 = 0−2) are observed. Analysis of the spectrum results in 240 assignments, including 196 new assignments and 56 assignments above the approximate 17 000 cm-1 dissociation threshold. The data are fit to an anharmonic oscillator model with a standard deviation of 3.3 cm-1.
Offshoring and unemployment: The role of search frictions labor mobility ☆

Abstract In a two-sector, general-equilibrium model with labor-market search frictions, we find that the wage increases and sectoral unemployment decreases upon offshoring in the presence of perfect intersectoral labor mobility. If, as a result, labor moves to the sector with the lower (or equal) vacancy costs, there is an unambiguous decrease in economywide unemployment. With imperfect intersectoral labor mobility, unemployment in the offshoring sector can rise, with an unambiguous unemployment reduction in the non-offshoring sector. Imperfect labor mobility can result in a mixed equilibrium in which only some firms offshore, with unemployment in the offshoring sector rising.
Mechanisms of Silica and Titania Colloidal Particle Formation from Metal Alkoxides

Control of the preparation of monodisperse particles for green body formation can be achieved by understanding the growth mechanism. Growth processes for colloidal silica and titania were followed by cryo-TEM, which allows direct observation of the particles in the liquid state. Structural development was tracked by quenching samples at successive reaction times. The preparation of silica particles involved the formation of ramified species which subsequently collapsed after reaching a certain size. In the titania system, initially small dense nuclei are observed which eventually form uniformly textured homogeneous particles.
Tyrosinase activity in a highly pigmented human melanoma and in negro skin.

SummaryThe comparison of the tyrosinase present in the skin of a 38-year-old male Negro with that present in highly pigmented metastatic melanoma in the same individual revealed a number of differences. In the skin, enzymic activity varied with the skin region, showed low specific activity, was confined to the particulate fraction, and showed 12-25% tyrosine carboxylgroup incorporation into melanin. Melanoma tyrosinase activity was similar in the various metastases, showed high specific activity, was present in both the particulate and soluble fractions, and showed only 9.4-9.8% tyrosine carboxyl-group incorporation into melanin. Three tyrosinase isozymes were present in the melanomas. Prolonged storage at −27° of the melanomas increased tyrosinase activity 2-6-fold. Enzymic inhibitors may have a role in the control of tyrosinase activity in melanoma.
A novel exon in the human Ca2+-activated Cl- channel Ano1 imparts greater sensitivity to intracellular Ca2+

Anoctamin 1 (Ano1; TMEM16A) is a Ca(2+)-activated Cl(-) channel (CACC) expressed in interstitial cells of Cajal. The mechanisms by which Ca(2+) regulates Ano1 are incompletely understood. In the gastrointestinal tract, Ano1 is required for normal slow wave activity and is involved in regulating cell proliferation. Splice variants of Ano1 have varying electrophysiological properties and altered expression in disease states. Recently, we identified a transcript for human Ano1 containing a novel exon-"exon 0" upstream of and in frame with exon 1. The electrophysiological properties of this longer Ano1 isoform are unknown. Our aim was to determine the functional contribution of the newly identified exon to the Ca(2+) sensitivity and electrophysiological properties of Ano1. Constructs with [Ano1(+0)] or without [Ano1(-0)] the newly identified exon were transfected into human embryonic kidney-293 cells. Voltage-clamp electrophysiology was used to determine voltage- and time-dependent parameters of whole cell Cl(-) currents between isoforms with varying concentrations of intracellular Ca(2+), extracellular anions, or Cl(-) channel inhibitors. We found that exon 0 did not change voltage sensitivity and had no impact on the relative permeability of Ano1 to most anions. Ano1(+0) exhibited greater changes in current density but lesser changes in kinetics than Ano1(-0) in response to varying intracellular Ca(2+). The CACC inhibitor niflumic acid inhibited current with greater efficacy and higher potency against Ano1(+0) compared with Ano1(-0). Likewise, the Ano1 inhibitor T16Ainh-A01 reduced Ano1(+0) more than Ano1(-0). In conclusion, human Ano1 containing exon 0 imparts its Cl(-) current with greater sensitivity to intracellular Ca(2+) and CACC inhibitors.
Where Did the Linker-Payload Go? A Quantitative Investigation on the Destination of the Released Linker-Payload from an Antibody-Drug Conjugate with a Maleimide Linker in Plasma

The reactive thiol of cysteine is often used for coupling maleimide-containing linker-payloads to antibodies resulting in the generation of antibody drug conjugates (ADCs). Currently, a numbers of ADCs in drug development are made by coupling a linker-payload to native or engineered cysteine residues on the antibody. An ADC conjugated via hinge-cysteines to an auristatin payload was used as a model in this study to understand the impact of the maleimide linkers on ADC stability. The payload was conjugated to trastuzumab by a protease-cleavable linker, maleimido-caproyl-valine-citruline-p-amino-benzyloxy carbonyl (mcVC-PABC). In plasma stability assays, when the ADC (Trastuzumab-mcVC-PABC-Auristatin-0101) was incubated with plasma over a 144-h time-course, a discrepancy was observed between the measured released free payload concentration and the measured loss of drug-to-antibody ratio (DAR), as measured by liquid chromatography–mass spectrometry (LC–MS). We found that an enzymatic release of payload from ...
The Treatment of Infection Stones with Penicillin

AbstractThe use of oral penicillin therapy is important in the management of renal stones secondary to Proteus mirabilis urinary tract infections. In 16 of 20 patients (80 per cent) with struvite renal calculi infected with Proteus mirabilis a sterile urine was achieved with appropriate penicillin therapy and diminution in stone size occurred in at least 2 cases. The rationale, supporting data and therapeutic uses are discussed.
Popper’s Progress

Our emphasis has been on Karl Popper as representing a current of thought with deep roots in history; a current of thought that we will call positivist. It reflects the belief in a process of cumulative learning through experience that has drawn mankind out of dark and ancient depths towards the single lodestone of truth. It projects an image of history as the slow but certain triumph of a reason that, through the trials of experience, learns to differentiate the true from the false, piercing the clouds of obscurantism and superstition, turning the vast spaces of ignorance into light.1
How central are judgment and agency to epistemology

Ernest Sosa’s Judgment and Agency marks an important change from his earlier work in epistemology. While belief was at the center of his earlier approach to epistemological issues, a far more sophisticated mental state, judgment, plays the central role here. This paper examines the significance of this change in focus, and argues that there is reason to favor the earlier belief-centered approach over this new judgment-centered account.
Relation Between Glance-Times at an in-Vehicle HMI System and Number of Letters Displayed on It

This paper reports the relation between glance-times at the screen of an in-vehicle HMI (Human-Machine Interface) system near the driver’s seat and the number of letters and characters dis-played on it. Our experimental results and discussion provide the fundamentals of a design method for HMIs operated by drivers to minimize glance-times. We conducted an experiment with a driving simulator to collect such data as time to read words displayed on in-vehicle HMIs while participants drove on an experimental course. The results indicate that for driving safety, the number of letters and characters displayed on an in-vehicle HMI screen should be less than 120.
Therapeutic Use of Cytokines: Animal Models

Although many clinical studies of the effects of burn or other major traumatic injury have been carried out and have yielded important information, many questions of mechanism may not be asked in this setting for practical or ethical reasons. Animal models afford the opportunity to study these questions. This has been especially since syngeneic strains are available where all animals are essentially twins. Furthermore, the use of congenic strains allows the choice of animals different at a single genetic locus where, for example, cells may be transferred between animals and recovered later to identify homing or cellular activities in different organs of the body.
Is it treasure or a worthless piece of ship

In response to a recent increase in treasure hunting ventures, and the ethical positions taken by professional archaeological associations, the Council of American Maritime Museums and the International Congress of Maritime Museums have developed specific guidelines and recommendations for the collecting and exhibiting of archaeological materials. In particular, objects from commercially exploited archaeological sites are prohibited, to reduce the market in these artifacts and prevent the perception that museums foster and/or condone the looting of archaeological shipwreck sites.
Optimal Federalism Across Institutions: Theory and Applications from Environmental and Health Care Policies

Instead of turning immediately to federal legislation, the question of “federalism” then becomes: When is federal action appropriate, and when should the problem be addressed by the states? Over the past fifteen years, courts and legal scholars have attempted to answer this question. This Article presents a framework that provides a new technique to answer this question. This framework analyzes federalism across enactment, implementation, and enforcement institutions, by examining economies and diseconomies of scale inherent in each of these institutions. This Article then applies the framework to a
A Multi-Conditional Correlation Statistics for Detecting Spatio-Temporally Correlated Firing Patterns

A multi-conditional correlation statistic is developed to detect the spatio-temporal firing patterns in a network of biological neurons. This conditional statistic measures the conditional probability of firing of the next spike for a neuron in relation to the firing times of spikes in other spike trains. It detects the conditions under which firing in neurons occur in recorded spike trains. Once the multi-conditional probability density function (c.p.d.f.) is established, the probability of which of the n recorded neurons contributes to the combinatorical firing of a neuron can be determined.
PCSM-02SURVIVORSHIP CARE PLANNING IN THE NEURO-ONCOLOGY CLINIC

A 2006 Institute of Medicine report recommended that cancer survivorship care planning be implemented into comprehensive care of the patient with cancer. Survivorship care planning is a planned approach to addressing 1) prevention of late effects, 2) surveillance for cancer progression or late effects, 3) intervention for symptoms arising from the cancer or its treatment, and 4) coordination of care amongst healthcare providers. In response to the recommendations, we developed a cancer survivor component of care that was added to the current clinical program and delivered by advanced practice nurses. Survivorship care planning was implemented at completion of the concomitant phase of treatment, upon completion of the adjuvant phase of treatment, and at any time treatment changed. A survivorship care plan template was developed as part of the electronic medical record (EMR) and used to guide survivor discussions. The care plan addressed the four key aspects above with recommendations for interventions related to each aspect. Inclusion of the care plan in the EMR allowed all neuro-oncology team members to provide input into and be able to view the plan collectively; the plan was also shared electronically with the primary provider. Ongoing symptoms were identified using patient self-report data to supplement the examination, and addressed on an individual basis with additional referral to a web-based self-management program. Research about program efficacy is ongoing. Challenges were encountered in identifying reimbursement options and program adaptation to a wide variety of tumor types. A multidisciplinary approach was found to be most helpful in implementing survivorship care planning into comprehensive care for the person with a brain tumor.
Seismic modeling with radial basis function-generated finite differences (RBF-FD) – a simplified treatment of interfaces

Abstract In a previous study of seismic modeling with radial basis function-generated finite differences (RBF-FD), we outlined a numerical method for solving 2-D wave equations in domains with material interfaces between different regions. The method was applicable on a mesh-free set of data nodes. It included all information about interfaces within the weights of the stencils (allowing the use of traditional time integrators), and was shown to solve problems of the 2-D elastic wave equation to 3rd-order accuracy. In the present paper, we discuss a refinement of that method that makes it simpler to implement. It can also improve accuracy for the case of smoothly-variable model parameter values near interfaces. We give several test cases that demonstrate the method solving 2-D elastic wave equation problems to 4th-order accuracy, even in the presence of smoothly-curved interfaces with jump discontinuities in the model parameters.
The Tubulointerstitial Pathophysiology of Progressive Kidney Disease

Accumulating evidence suggests that the central locus for the progression of CKD is the renal proximal tubule. As injured tubular epithelial cells dedifferentiate in attempted repair, they stimulate inflammation and recruit myofibroblasts. At the same time, tissue loss stimulates remnant nephron hypertrophy. Increased tubular transport workload eventually exceeds the energy-generating capacity of the hypertrophied nephrons, leading to anerobic metabolism, acidosis, hypoxia, endoplasmic reticulum stress, and the induction of additional inflammatory and fibrogenic responses. The result is a vicious cycle of injury, misdirected repair, maladaptive responses, and more nephron loss. Therapy that might be advantageous at one phase of this progression pathway could be deleterious during other phases. Thus, interrupting this downward spiral requires narrowly targeted approaches that promote healing and adequate function without generating further entry into the progression cycle.
Trait mindfulness at work: A meta-analysis of the personal and professional correlates of trait mindfulness

ABSTRACTPopular and academic press alike have concluded that mindfulness significantly benefits healthy individuals as well as those suffering from physical and psychological problems. Workplace interventions, clinical therapies, and popular self-help programs aimed at enhancing mindfulness abound, and research has demonstrated the efficacy of such mindfulness interventions in enhancing mindful states. It is of importance to note that research also suggests the average frequency with which individuals experience states of mindfulness varies from person to person, underscoring the existence of a dispositional tendency toward mindfulness—trait mindfulness. We meta-analytically cumulate the results of 270 independent studies (N = 58,592 adults from nonclinical samples) of trait mindfulness in order to explore its personal and professional correlates. Results suggest the benefits of trait mindfulness extend to both personal and professional domains. With regards to personal benefits, trait mindfulness was fou...
Nutrient Use and Remineralization

This chapter discusses how nutrients are acquired and assimilated, the relative amounts needed in different systems, the availability of nutrients, and the crucial concept of nutrient limitation. Nutrients are critical basal resources in aquatic systems because they often limit primary production or heterotrophic activity. Understanding ecosystem production, nutrient pollution, and interactions among heterotrophs, autotrophs, and their environment requires an elucidation of nutrient dynamics. Nutrients are acquired in a variety of forms by organisms. Most primary producers and many bacteria have the ability to use inorganic nutrients, such as nitrate or phosphate. In a case that stretches the definition of autotroph, algae such as the dinoflagellates can ingest particulate material for its nitrogen and phosphorus content and to meet part of their carbon requirements. Most animals and heterotrophic eukaryotic unicellular organisms acquire their nutrients in organic form.
On Infinitely Generated Fuchsian Groups

The study of fundamental domains for Fuchsian groups is classical and has been revived recently in connection with t he theory of Teichmuller spaces. In t his theory, the finitely generated Fuchsian groups play a central role and most of the results on fundamental polygons are valid only for these groups.
COMPASS| Measuring the Journalism Crisis: Developing New Approaches That Help the Public Connect to the Issue

Despite academics and media critics warning that cutbacks from the journalism crisis may be harming democratic values, a majority of the public is unaware of the financial struggles plaguing the industry. In this article, I argue that more communication scholars should publish research that is accessible to the broader public to help raise public awareness of this pivotal issue. Political economy, I argue, is well suited to this task, given its emphasis on merging research with action. I detail three key ways scholars can help the public connect to the journalism crisis: (1) by “localizing” the data to allow people to see how the crisis is impacting their community, (2) by “humanizing” the research to make the findings more relatable, and (3) by testing and refuting common refrains related to the crisis.
Integration of basic and clinical sciences: Faculty perspectives at a U.S. Dental School

Although dental education has traditionally been organized into basic sciences education (first and second years) and clinical education (third and fourth years), there has been growing interest in ways to better integrate the two to more effectively educate students and prepare them for practice. Since 2012, The University of Texas School of Dentistry at Houston (UTSD) has made it a priority to improve integration of basic and clinical sciences, with a focus to this point on integrating the basic sciences. The aim of this study was to determine the perspectives of basic and clinical science faculty members regarding basic and clinical sciences integration and the degree of integration currently occurring. In October 2016, all 227 faculty members (15 basic scientists and 212 clinicians) were invited to participate in an online survey. Of the 212 clinicians, 84 completed the clinician educator survey (response rate 40%). All 15 basic scientists completed the basic science educator survey (response rate 100%). The majority of basic and clinical respondents affirmed the value of integration (93.3%, 97.6%, respectively) and reported regular integration in their teaching (80%, 86.9%). There were no significant differences between basic scientists and clinicians on perceived importance (p=0.457) and comfort with integration (p=0.240), but the basic scientists were more likely to integrate (p=0.039) and collaborate (p=0.021) than the clinicians. There were no significant differences between generalist and specialist clinicians on importance (p=0.474) and degree (p=0.972) of integration in teaching and intent to collaborate (p=0.864), but the specialists reported feeling more comfortable presenting basic science information (p=0.033). Protected faculty time for collaborative efforts and a repository of integrated basic science and clinical examples for use in teaching and faculty development were recommended to improve integration. Although questions might be raised about the respondents’ definition of “integration,” this study provides a baseline assessment of perceptions at a dental school that is placing a priority on integration.