cssi/SciSciGPT-SciSciNet huggingface dataset:
Scaling Global Warming Impacts on Ocean Ecosystems: Lessons From a Suite of Earth System Models

An important technique used by climate modelers to isolate the impacts of increasing greenhouse gasses on Earth System processes is to simulate the impact of an abrupt increase in carbon dioxide. The spatial pattern of change provides a “fingerprint” that is generally much larger than natural variability. Insofar as the response to radiative forcing is linear (the impact of quadrupling CO2 is twice the impact of doubling CO2) this fingerprint can then be used to estimate the impact of historical greenhouse gas forcing. However the degree to which biogeochemical cycles respond linearly to radiative forcing has rarely been tested. In this paper, we evaluate which ocean biogeochemical fields are likely to respond linearly to changing radiative forcing, which ones do not, and where linearity breaks down. We also demonstrate that the representation of lateral mixing by mesoscale eddies, which varies significantly across climate models, plays an important role in modulating the breakdown of linearity. Globally integrated surface rates of biogeochemical cycling (primary productivity, particulate export) respond in a relatively linear fashion and are only moderately sensitive to mixing. By contrast, the habitability of the interior ocean (as determined by hypoxia and calcite supersaturation) behaves nonlinearly and is very sensitive to mixing. This is because the deep ocean, as well as certain regions in the surface ocean, are very sensitive to the magnitude of deep wintertime convection. The cessation of convection under global warming is strongly modulated by the representation of eddy mixing. respond in a relatively linear fashion and are moderately sensitive to mixing. By contrast, the habitability of the interior ocean (as determined by hypoxia and calcite supersaturation) behaves nonlinearly and is very sensitive to mixing. This is because the deep ocean, as well as certain regions in the surface ocean, are very sensitive to the magnitude of deep wintertime convection. The cessation of convection under global warming is strongly modulated by the representation of eddy mixing.
Interpretable Segmentation of Amyloid-β Stained Whole Slide Images of Brain Tissue

Neurodegenerative disease pathologies have been reported in both grey matter (GM) and white matter (WM) with different density distributions, an automated separation task of GM/WM would be extremely advantageous for aid in neuropathologic deep phenotyping. Standard segmentation methods typically involve manual annotations, where a trained researcher traces the delineation of GM/WM in ultra-high-resolution Whole Slide Images (WSIs). This method can be time-consuming and subjective, preventing the analysis of large amounts of WSIs in a scalable way. In this paper, we propose an automated segmentation pipeline combining a Convolutional Neural Network (CNN) module for segmenting GM/WM regions and a post-processing module to remove artifacts/residues of tissues as well as generate XML annotations that can be visualized via Aperio ImageScope. First, we investigate two baseline models for medical image segmentation: FCN, and U-Net. Then we propose a new patch-based approach, ResNet-Patch, to classify the GM/WM/background regions. In addition, we integrate a Neural Conditional Random Field (NCRF) module, ResNet-NCRF, to model and incorporate the spatial correlations among neighboring patches. Although their mechanisms are greatly different, both U-Net and ResNet-Patch/ResNet-NCRF achieve Intersection over Union (IoU) of more than 90% in GM and more than 80% in WM, while ResNet-Patch achieves 1% superior to U-Net with lower variance among various WSIs. ResNet-NCRF further improves the IoU by 3% for WM compared to ResNet-Patch before post-processing. We also apply gradient-weighted class activation mapping (Grad-CAM) to interpret the segmentation masks and provide clinical explanations and insights.
Directional Migration of Breast Cancer Cells Hindered by Induced Electric Fields May Be Due to Accompanying Alteration of Metabolic Activity.

Background: Induced electric fields (iEFs) control directional breast cancer cell migration. While the connection between migration and metabolism is appreciated in the context of cancer and metastasis, effects of iEFs on metabolic pathways especially as they relate to migration, remain unexplored. Materials and Methods: Quantitative cell migration data in the presence and absence of an epidermal growth factor (EGF) gradient in the microfluidic bidirectional microtrack assay was retrospectively analyzed for additional effects of iEFs on cell motility and directionality. Surrogate markers of oxidative phosphorylation (succinate dehydrogenase [SDH] activity) and glycolysis (lactate dehydrogenase activity) were assessed in MDA-MB-231 breast cancer cells and normal MCF10A mammary epithelial cells exposed to iEFs and EGF. Results: Retrospective analysis of migration results suggests that iEFs increase forward cell migration speeds while extending the time cells spend migrating slowly in the reverse direction or remaining stationary. Furthermore, in the presence of EGF, iEFs differentially altered flux through oxidative phosphorylation in MDA-MB-231 cells and glycolysis in MCF10A cells. Conclusions: iEFs interfere with MDA-MB-231 cell migration, potentially, by altering mitochondrial metabolism, observed as an inhibition of SDH activity in the presence of EGF. The energy intensive process of migration in these highly metastatic breast cancer cells may be hindered by iEFs, thus, through hampering of oxidative phosphorylation.
Baseline Modified Glasgow Prognostic Score Associated with Survival in Metastatic Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors

BACKGROUND The modified Glasgow prognostic score (mGPS), a clinical tool that incorporates albumin and C-reactive protein, has proven useful in the prognostication of multiple cancers. Several immune checkpoint inhibitors (ICIs) have been approved for the treatment of metastatic urothelial cell carcinoma (mUC), but a prognostic biomarker is needed. We investigated the impact of mGPS on survival outcomes in patients with mUC receiving ICIs. MATERIALS AND METHODS We retrospectively reviewed patients with mUC treated with ICIs (programmed cell death protein 1 or programmed cell death ligand 1 inhibitors) at Winship Cancer Institute from 2015 to 2018. Overall survival (OS) and progression-free survival (PFS) were measured from the start date of ICI until death or clinical or radiographic progression, respectively. mGPS was defined as a summary score with one point given for C-reactive protein >10 mg/L and/or albumin <3.5 g/dL. Univariate (UVA) and multivariate (MVA) analyses were carried out using Cox proportional hazard model. These outcomes were also assessed by Kaplan-Meier analysis. RESULTS A total of 53 patients were included with a median follow-up 27.1 months. The median age was 70 years, with 84.9% male and 20.8% Black. Baseline mGPS was 0 in 43.4%, 1 in 28.3% and 2 in 28.3%. Increased mGPS at the time of ICI initiation was associated with poorer OS and PFS in UVA, MVA, and Kaplan-Meier analyses. CONCLUSION The mGPS may be a useful prognostic tool in patients with mUC when treatment with ICI is under consideration. These results warrant a larger study for validation. IMPLICATIONS FOR PRACTICE The ideal prognostic tool for use in a busy clinical practice is easy-to-use, cost-effective, and capable of accurately predicting clinical outcomes. There is currently no universally accepted risk score in metastatic urothelial cell carcinoma (mUC), particularly in the immunotherapy era. The modified Glasgow prognostic score (mGPS) incorporates albumin and C-reactive protein and may reflect underlying chronic inflammation, a known risk factor for resistance to immune checkpoint inhibitors (ICIs). This study found that baseline mGPS is associated with survival outcomes in patients with mUC treated with ICIs and may help clinicians to prognosticate for their patients beginning immunotherapy.
Dynamic Irrigation Management under Temporal and Spatial Variability

Recent studies report that agricultural productivity must improve significantly in the near future to meet the increase in demand due to rapid growth of the world population. One way to improve agricultural productivity is to increase irrigation. However, fresh water scarcity, increasing production costs, and the climate change necessitate sustainable and efficient methods for irrigation, which accounts for nearly seventy percent of global fresh water usage. This paper studies dynamic irrigation management under uncertainty taking into account temporal variability and spatial soil heterogeneity of the field. We show that an (s, S)-type irrigation policy is optimal for the soil structure that is radially homogeneous. Building on this result, we also derive performance bounds and effective heuristic policies for the general case that allows radial soil heterogeneity. Our numerical study reveals that the proposed dynamic irrigation policies can improve farmers' expected net benefit (yield revenue net of irrigation cost) and water savings significantly over the commonly used irrigation policies in practice.
COMMENTARY: The Endowment Model Is Just Active Management

Endowed institutions and other investors, if they choose to be active rather than indexed, can benefit by considering as potential investments every asset class and strategy in the world. Such unconstrained investing is supported by finance theory, which says that constraints on active bets are always costly in terms of return, conditional on the active management in question being successful (adding alpha) in the first place. Endowment funds are free to do many things that other investors are not, making them more likely to succeed at active management than other classes of institutions or individuals. However, the performance of these funds has varied materially over time, with a recent long period of underperformance, so the success of the endowment model is not guaranteed. Part of this underperformance is due to the high costs of the alternative investments that distinguish endowment-model portfolios from more traditional portfolios, so investors adopting the endowment model should pay special attention to fund fees and other costs. TOPICS:Portfolio theory, portfolio construction, foundations & endowments, performance measurement Key Findings ▪ The endowment model of investing is just a form of active management and is not a magic formula for making (or losing) money. ▪ Many endowed institutions are free to make substantial bets—on alternative investments, large deviations from policy portfolios, and unconventional structures—that other institutions cannot. ▪ This freedom should increase the alpha earned by endowments, provided that they are capable of earning alpha in the first place.
Taxes, Transfers, Progressivity, and Redistribution: Part 3

We present a more thorough analysis of the progressivity and regressivity of tax increases and spending reductions. Our analysis highlights an important distinction between low-end and high-end progressivity. We refer to a policy as having low-end progressivity if it places smaller burdens (relative to income) on the poorest households than on the population as a whole, so that it reduces inequality at the low end of the income distribution by increasing the poorest households’ share of disposable income. We refer to a policy as having high-end progressivity if it places larger burdens (relative to income) on the richest households than on the population as a whole, so that it reduces inequality at the high end of the income distribution by lowering the richest households’ share of disposable income. We present measures of low-end, high-end, and overall progressivity for 11 tax increases and eight spending cuts. Many of the policy options are consistently progressive or consistently regressive throughout the income distribution. However, several policies, including some proposed means tests for social insurance programs and some individual income tax base broadening measures, are progressive at the low end and regressive at the high end. Those policies place smaller burdens (relative to income) on both the poorest and the richest households while placing larger burdens (relative to income) on some or all households between those extremes.
Model-based inversion for a shallow ocean application

A model-based approach to invert or estimate the sound speed profile (SSP) from noisy pressure-field measurements is discussed. The resulting model-based processor (MBP) is based on the state-space representation of the normal-mode propagation model. Using data obtained from the well-known Hudson Canyon experiment, a noisy shallow water ocean environment, the processor is designed and the results compared to those predicted using various propagation models and data. It is shown that the MBP not only predicts the sound speed quite well, but also is able to simultaneously provide enhanced estimates of both modal and pressure-field measurements which are useful for localization and rapid ocean environmental characterization.
Southern Four Wheel Drive Ass’n v. U.S. Forest Serv.

The United States District Court for the Western District of North Carolina determined the Nantahala National Forest properly amended the Forest Plan to prohibit and restrict vehicular access to the Upper Tellico Off Highway Vehicle System. On summary judgment, the court found the Forest Service followed the appropriate procedures in deciding that erosion and sedimentation related to off-roading were imperiling the native brook trout.
The structural and acoustic properties of sputtered aluminum nitride on silicon

The structural and acoustic properties of reactively sputtered aluminum nitride (AlN) on silicon have been characterized. The AlN films were grown on (100) silicon wafers, having a 200 nm thick layer of PECVD silicon nitride, at substrate temperatures in the 300/spl deg/C to 500/spl deg/C range, with a low background sputter pressure, and a high deposition rate. X-ray, atomic force microscopy and transmission electron microscopy measurements defined the structural properties. Surface acoustic wave (SAW) propagation measurements in the frequency range from 50 MHz to 1.5 GHz defined the acoustic properties. A strong correlation was found between the structural properties and the measured SAW velocity and propagation loss characteristics. One micrometer thick films with high intensity (002) plane x-ray diffraction intensities, closely packed uniform grains, approximately 30 nm in diameter, and a surface roughness less than 10 nm, had SAW velocity dispersion characteristics, coupling factors and propagation losses close to those of epitaxial AlN. Electron diffraction characteristics taken over several grains perpendicular to the columnar structure resembled a single crystal diffraction pattern. Deviation of the films structural properties from these epitaxial-like conditions was observed when more than one-half percent of oxygen was incorporated in the films.
Synthesis and degradation of a brain-specific protein (S100 protein) by clonal cultured human glial cells.

Abstract A technique for specifically and quantitatively isolating radioactively labeled S100 protein, a brain-specific protein, from cultured human glial cells (CHB4) has been developed. The necessary specificity is achieved by precipitation of labeled S100 in antibody excess with carrier S100 and anti-S100 antibody, followed by acrylamide gel electrophoresis of the solubilized precipitate in the presence of sodium dodecyl sulfate. The specificity of the method is shown by applying the technique to cell lines which do not synthesize S100. Quantitative recovery is demonstrated by a second precipitation from a labeled glial cell extract. The differential rate of S100 protein synthesis in confluent CHB4 cells is 0.06%. The S100 protein in confluent cultures of CHB4 appears to be quite stable when compared to total protein, and is not rapidly degraded.
Chapter 3 Mapping Mean Annual Precipitation Using Trivariate Kriging

Theme Mean annual precipitation is arguably one of the most significant “bottom-up” influences in temperate large mammal systems, as precipitation typically governs plant phenology and productivity in spring and summer while limiting accessibility and distribution of forage in winter. Mean annual precipitation exhibits marked spatial patterns in mountainous regions such as Yellowstone National Park, resulting in strong spatial gradients in snow pack ( Chapter 6 by Watson et al., this volume) and meadow phenology ( Chapter 7 by Thein et al., this volume). These spatial patterns have strong influences on large herbivore population dynamics, distribution and movement, and may play an important role in the interactions between predators and prey. Accurately capturing regional variation in precipitation patterns therefore is fundamental to understanding wildlife dynamics and ecosystem processes in general. We produced a map of mean annual precipitation using objective methods involving the development of a variant of kriging, a statistical technique for spatial interpolation between values at known locations. This appears to be a new approach to precipitation mapping, that we termed trivariate zonal ordinary kriging. Rather than treating elevation as a secondary variable, as in cokriging, or a deterministic influence, as in universal kriging, trivariate zonal ordinary kriging considers elevation as a component of the spatial separation between any two locations.
Health Profile Preferences of Hepatitis C Patients

The side effects of interferon-α for chronic hepatitis C are well-known. Patients may differ with respect to their tolerance of these side effects and also with respect to their individual preferences. We administered a brief questionnaire to 67 outpatients with hepatitis C virus infection. Patients were asked to make hypothetical choices between six-month profiles of health. The results were as follows: (1) patients preferred to expedite rather than postpone intervals of poor health; (2) preferences of patients with low quality-of-life were quite similar to preferences of healthier patients; (3) patients' choices satisfied transitivity; (4) patients' choices satisfied preferential independence; and (5) patients gave a variety of reasons for their choices. These results corroborate other investigations of health preferences, and serve to introduce the field of preference elicitation to gastroenterologists.
Numerical models of rotating stars

Rotating stars are modelled by the equilibrium solution of the Euler equations for a compressible, inviscid fluid subject to selfgravitational and centrifugal forces. These are many difficulties in trying to solve this equation directly. Here, a new method is described, based on discretizing the functional E (rho) and the constraint for density and minimizing the resulting finite dimensional function. (BJ)
Electromagnetic crosstalk penalty in serial fiber optic modules

Electromagnetic crosstalk poses a serious problem within today's advanced serial communication modules. A major detrimental effect is the degradation of receiver sensitivity in the presence of crosstalk noise. The mitigation of crosstalk penalty becomes increasingly more challenging as data rates increase for higher throughput and as module sizes shrink for increased port density. This paper is a study of the primary sources of crosstalk penalty in a 2.5 GB/s serial fiber optic transceiver and a 10 Gb/s serial fiber optic transponder. A novel method for quantifying crosstalk penalty by observing a receiver's bit-error-ratio (BER) versus transmitter to receiver signal phase is proposed. A simple coupled microstrip transmission line model is explored to demonstrate inductive crosstalk coupling.
Changes in dopamine transporter binding in nucleus accumbens following chronic self‐administration cocaine: Heroin combinations

Concurrent use of cocaine and heroin (speedball) has been shown to exert synergistic effects on dopamine neurotransmission in the nucleus accumbens (NAc), as observed by significant increases in extracellular dopamine levels and compensatory elevations in the maximal reuptake rate of dopamine. The present studies were undertaken to determine whether chronic self-administration of cocaine, heroin or a combination of cocaine:heroin led to compensatory changes in the abundance and/or affinity of high- and low-affinity DAT binding sites. Saturation binding of the cocaine analog [(125) I] 3β-(4-iodophenyl)tropan-2β-carboxylic acid methyl ester ([(125) I]RTI-55) in rat NAc membranes resulted in binding curves that were best fit to two-site binding models, allowing calculation of dissociation constant (Kd ) and binding density (Bmax ) values corresponding to high- and low-affinity DAT binding sites. Scatchard analysis of the saturation binding curves clearly demonstrate the presence of high- and low- affinity binding sites in the NAc, with low-affinity sites comprising 85 to 94% of the binding sites. DAT binding analyses revealed that self-administration of cocaine and a cocaine:heroin combination increased the affinity of the low-affinity site for the cocaine congener RTI-55 compared to saline. These results indicate that the alterations observed following chronic speedball self-administration are likely due to the cocaine component alone; thus further studies are necessary to elaborate upon the synergistic effect of cocaine:heroin combinations on the dopamine system in the NAc.
Chemical dynamics Noisy waves

Noise, is familiar from communications, where a single parameter such as voltage varies with time. Usually it is a nuisance, but sometimes, because of the peculiar phenomenon known as stochastic resonance, it is a boon, increasing signal strength. Noise is also present in many extended natural phenomena, such as calcium-ion waves in the brain. Are there also extended systems in which the noise can increase some collective, or coherent, dynamical property? Such spatiotemporal stochastic resonance has now been achieved experimentally for the first time.
Shuttle Avionics Hardware Programs

Abstract The Shuttle Orbiter is designed to emphasize service to a variety of payloads. For this, the avionics subsystems must be a balance of light weight and low risk hardware with sufficient redundancy to allow safe vehicle return in the event of equipment malfunction. Installation must allow ready access for maintenance to support a short ground turn-around between flights. This paper describes the hardware features selected to meet the avionics objectives. Currently, subsystems are in the development laboratories to verify hardware and software interfaces. Qualification testing has started and installation in the first Orbiter will begin this Fall.
The Effect of User-Specified Language Elements on Learning to Program

AbstractIt was hypothesized that there is an advantage for novice programmers who were asked to define elements of the language they were learning. Members of an experimental group specified their own operation codes for a language, whereas the control group used fixed codes. On a programming exercise, the experimental group performed worse than the control group. Analysis shows that the use of fixed operation codes and the subjects general aptitude are positively related to scores on the exercise. For the high aptitude subjects, the best predictor of success on the exercise is their aptitude score; for the low aptitude subjects, the best predictor is the form of operation code.
Effect of x-irradiation on the DNA content of individual nuclei of rabbit bone marrow.

Abstract 1. 1. Feulgen microspectrophotometric studies of DNA were conducted on individual nuclei of non-irradiated and irradiated femoral marrows of rabbits exposed to 800 r hemi-body X-irradiation. 2. 2. The major portion of the measured marrow nuclei from the non-irradiated marrow cells are in the range between 6 and 12 × 10 −9 mg of DNA per nucleus. These cells have been designated as synthesizing cells. 3. 3. The main consequence of X-irradiation to the exposed femurs has been to reduce the number of synthesizing cells. Studies conducted at 24 and 48 hours post-irradiation reveal a consistent decrease in the number of synthesizing cells. At intervals of X-irradiation less than 24 hours, the results were variable although indicative of a decrease in synthesizing cells. 4. 4. Studies on comparable nuclear sizes of X-rayed and non-X-rayed femoral marrow reveal a reduction of synthesizing cells in the larger nuclei (2.7–3.5 + arbitrary units). In the case of nuclear size ranges below 2.7 and erythroblasts (nuclear size range 2.0–2.7 arbitrary units) there are no significant effects of X-irradiation.
Unique topology of language processing brain network: A systems-level biomarker of schizophrenia

Objective Schizophrenia is a severe and heritable brain disorder. Language impairment has been hypothesized to spur its onset and underlie the characteristic symptoms. In this study, we investigate whether altered topological pattern of the language processing brain network exists and could be a potential biomarker of schizophrenia. We hypothesized that both patients with schizophrenia and the genetic high risk population would show significantly weakened efficiencies of the network hubs for normal language processing, especially at left inferior frontal and bilateral temporal lobes.
Paleobiology and the origins of avian flight

When interpreting the paleobiology of long extinct taxa, new fossils, and reinterpretations of well-known fossils, sharply at odds with conventional wisdom never seem to cease popping up. Given the vagaries of the fossil record, current notions of near resolution of many of the most basic questions about long-extinct forms should probably be regarded with caution. Even major aspects of the paleobiology of intensely studied, recently extinct taxa (<10,000 yrs.) remain unresolved [e.g., the cause(s) of late Pleistocene large-mammal disappearances (1) and the lifestyles of specialized forms (sabre-tooths) (2)]. Little wonder then that so fascinating a subject as the origins of birds and bird flight, both of which almost surely occurred more than 150 million years ago, have stirred such publicly visible and intense, nearly century-long, controversies (3). In this context, perhaps the most hotly debated and fundamental issue relates to the origin of avian flight: Did proto-birds take to the air as arboreal gliders where gravity was the primary source of flying energy (from the “trees-down”), or as swift, cursorial ground dwellers (from the “ground-upward”)? In PNAS, Alexander et al. (4) describe results of a novel “paleobiological” study: three-dimensional model-based, empirical data that provide important insight into this old question.
Integrating hormones and other biological factors into a developmental systems model of adolescent female sexuality.

This chapter discusses biological contributions to adolescent female sexual development and, based on a developmental systems framework, suggests future research directions.
Age related changes in emotional memory

Studies have found that emotionally evocative stimuli are better remembered than neutral stimuli, an effect called “emotional enhancement”. Researchers have also found that the elderly experience an overall decline in memory relative to the young. We hypothesized that the elderly may experience diminished emotional enhancement, and that this may be one factor contributing to overall memory decline in the elderly. We tested elderly and young subjects on tasks of emotional memory for words and faces. In both the elderly and young, a shift in memory favoring positive stimuli (as opposed to negative and neutral stimuli) was evident, this effect being slightly more marked in the elderly. We suggest that the effects seen in both groups may be due to a shift from the amygdala-hippocampal system to the prefrontal cortex over time. We suggest that the more marked response in the elderly may be due to age-related changes in these brain systems, causing a further shift towards memory for positive material.
Mitochondrial proliferation during neonatal renal compensatory growth.

Abstract Unilateral nephrectomy is associated with an increase in kidney mass in the contralateral kidney of young rabbits, progressively increasing from 8% at 1 day post-nephrectomy to 35% at 4 days post-nephrectomy. There is a preferential early increase in specific activity of mitochondrial cytochrome oxidase compared to monamine oxidase or malate dehydrogenase. Compensatory hypertrophy also stimulates quite early incorporation of radioactivity into mitochondrial inner membrane from 3 H-leucine and 14 C-glycerol.
Oxidative DNA damage and DNA mismatch repair pathway play an important role in failing human myocardium

Summary Background Heart failure is approaching epidemic proportions. However, DNA damage in the failing myocardium is not directly addressed yet. 8-Oxo-7,8-dihydrodeoxyguanine (8-oxoG) is a stable marker of DNA damage. The human Mut-Y homologue (hMYH) is a DNA mismatching repair enzyme promoting DNA reconstruction. The current study was designed to investigate whether DNA damage and repair as reflected in the levels of 8-oxoG and hMYH play an important role in the failing myocardium. Methods Donor and failing human myocardium were obtained from hearts of patients undergoing cardiac transplantation. DNA damage was determined by the presence of 8-oxoG. The protein level, activity, and expression of hMYH were determined by Western blot, the DNA gel-retardation binding assay and immunohistochemical staining (IHCS). The levels of apoptosis and apoptosis-related genes such as p53, p21-WAF, and caspase-3 were determined by TUNEL assay and IHCS. Results The levels of 8-oxoG indicating DNA damage significantly increased in the myocardium of failing hearts compared with donor subjects. On the other hand, the protein level and activity of the DNA repair enzyme, hMYH, was significantly decreased in CHF patients compared to donor subjects. Furthermore, apoptosis and apoptosis-related genes such as p53, p21-WAF, and caspase-3 were markedly increased in CHF myocardium. Conclusion Ongoing DNA damage is insufficiently repaired in the myocardium of failing hearts. This appears to be a major pathway responsible for myocardial failure in humans.
Inhibition of P-Glycoprotein ATPase Activity by Procedures Involving Trapping of Nucleotide in Catalytic Sites

Abstract Fluoroaluminate in combination with nucleotide inhibited ATPase activity of P-glycoprotein (Pgp) in plasma membranes and in pure reconstituted form. Low nucleotide concentrations were effective, e.g., half-maximal inhibition was obtained with 10 μ m MgATP. With MgATP or MgADP, reactivation occurred witht1/2= 7 min at 37°C. With 8-azido-ATP, UV irradiation of inhibited Pgp gave specific photolabeling of both nucleotide sites. Fluoroaluminate therefore provides a valuable tool for functional and structural characterization of P-glycoprotein and probably of other ABC transporters. 2-Azido-ATP, in combination with vanadate, fluoroaluminate, or beryllium fluoride, inhibited Pgp ATPase activity. Low concentrations of 2-azido-ATP were effective. However, after UV irradiation of the inhibited Pgp species, in no case was there evidence of covalent labeling of nucleotide sites. Therefore in the Pgp catalytic sites, under conditions of nucleotide trapping, there is no suitable amino acid side chain adjacent to the photoactivated 2-position of bound 2-azido-nucleotide, and 8-azido-ATP is the preferred photolabeling analog.
Synaptology of retinal terminals in the dorsal lateral geniculate nucleus of the cat

We have made a fine structural investigation of the synaptic patterns made by axon terminals of retinal ganglion cells in the dorsal lateral geniculate nucleus of the cat. We compared the retinal input to dendritic processes that bear clusters of large appendages with the retinal input to relatively smooth dendritic segments that have only a few isolated spines. The study was restricted to the portion of laminae A and A1 that receive central visual field input. We were able to completely reconstruct 33 individual terminal boutons from long series of consecutive thin sections. Retinal terminals that were presynaptic to dendritic appendages tended to occupy the central position in the complex synaptic zones of geniculate fine structure called glomeruli. These terminals were surrounded by significantly more profiles than retinal terminals that were presynaptic to dendritic stems and averaged twice as many synaptic contacts per terminal bouton. The retinal input to dentritic appendages was heavily involved in a specific synaptic pattern called the triadic arrangement while retinal input to dendritic stems was only lightly involved in triads. Dendritic appendages in triads received greater synaptic input from profiles with flattened vesicles than did the dendritic stems that were found in triads.
Managing and Leveraging Poverty: Implications for Teaching International Business

Over half of the world's population lives on less than $2 a day, and yet international business education to date has continued to ignore the not so well-off customers. We propose a holistic pedagogical approach to studying this market by considering the historical background of the growth of inequality and poverty in different regions of the world, as well as the criteria for segmenting various levels of poverty. A two-pronged approach is then suggested to addressing poverty issues: first, showing how traditional international business principles can be adapted to address the needs of the impoverished market segment using a macro (top-down) approach, and second, how this untapped market can be harnessed for profits while simultaneously uplifting them out of poverty using principles of social entrepreneurship as a micro (bottom-up) approach. Exemplar case studies are used to illustrate these strategies, as are catalytic factors such as investments in technology, education, and capital, which help alleviat...
Preoviposition activity of the black salt-marsh mosquito, Aedes taeniorhynchus (Díptera: Culicidae).

A laboratory study of the preoviposition behavior of Aedes taeniorhynchus (Wiedemann) is reported. Oviposition in this species was nocturnal in the laboratory and was preceded by a period of flight activity. This activity was exogenously controlled, being initiated by the onset of darkness on the day of oviposition. Flight occurred even in the presence of suitable oviposition substrates, and appeared to enhance the subsequent oviposition response. Females responded to stimuli from oviposition sites during this activity period. The response to moisture was reduced by a high ambient relative humidity, and the sensitivity of the females to a series of repellent salt solutions was reduced when the oviposition response was accelerated by delaying the presentation of substrates. These observations suggest that unnatural conditions imposed in the laboratory may result in acceptance of substrates not normally utilized in nature.
Characterization of cryogenic mechanical properties of aluminum-lithium alloy C-458

C-458 is one of the new-generation aluminum-lithium alloys being developed to address anisotropy and other drawbacks of previous aluminum-lithium alloys. Many of the future space applications (satellite/rocket components) under consideration for this alloy operate at temperatures well below room temperature; consequently, one focus of characterization in this study centered on the effect of decreasing temperature on the material properties of C-458. Another thrust was to evaluate any deleterious effects that could possibly result from long-term storage. Prior work has indicated that in previous-generation alloys, significant reduction in toughness occurs with extended aging. Exposure at 355K for 1,000 h was chosen to simulate the effect of long-term storage.
The Use of Problem‐Based Learning to Enhance MIS Education

Many colleges of business require a course in computer applications concepts, often consisting of spreadsheet and database applications. Quite often, students resist taking the class because they do not see any worth to it, it duplicates what they already have taken, and they already know much of what is purported to be taught in the class. Instructors too are often frustrated with this class. This article suggests that part of the problem is the method of instruction often used: lecture and demonstration of tools followed by end-of-chapter assignments. We propose that problem-based learning is an alternative instructional method that may produce more positive results for students. To examine this approach, a semester-long study involving 186 business school students enrolled in a computer applications concept course of seven different sections was conducted. Student motivation, computer self-efficacy, knowledge, and satisfaction were studied. Results strongly support a problem-based learning approach as an instructional approach to teaching this class. [I]t would be naive to regard PBL [Problem-based Learning] as having reached some final stage of development. Indeed, the problem-based approach is certainly not the end of innovation in professional education. Problem-oriented strategies are but one set of examples of the broader category of systemic educational thinking and approaches which emphasize learning from experience (Boud & Feletti, 1998a, p. 13).
Representations of Proportional Relationships: Are Children Part-Part or Part-Whole Reasoners?.

This research describes an intensive study undertaken to determine children's representational strategies for relational numbers (e.g. proportions, ratios, fractions). Relational numbers have three quantities associated with them: a whole and two parts. Given these three quantities, children can form a representation based on a part-whole relationship or on a part-part relationship. Fifteen children (6th, 7th, and 8th graders) solved fifteen probability problems which varied information content and quantitative relationships between the quantities expressed in the problems. A quantitative and qualitative analysis revealed that children prefer a part-part representation to solve problems with relational quantities.
Inter‐laboratory validation of EPA method 3200 for mercury speciation analysis using prepared soil reference materials

Determinations of the concentration of individual mercury species from environmental samples have increased significantly over the past decade. The techniques used for the determination of mercury species in soils or sediments generally involve a series of analytical steps (extraction, separation, detection) that may all be prone to systematic errors. An inter-laboratory validation study of the EPA draft method 3200 was conducted under the auspices of the United States Environmental Protection Agency on two specifically prepared soil matrices. The study was performed successfully by a limited number of participating laboratories. Evaluation of the data demonstrates that the method is more highly efficient for extracting the highly toxic methylmercury than inorganic mercury. The proposed method does not induce transformation of methylmercury to inorganic mercury. Copyright © 2004 John Wiley & Sons, Ltd.
Weak stochastic orderings and dependence measures

Many notions of dependence rely upon orderings of random pairs. These orderings are generally partial orders, and thus there are many pairs of random vectors which are not comparable. By using a weakened version of stochastic dominance, many new orderings, as well as corresponding dependence measures, are created. The application to stock market data is explored.
Experimental and Theoretical Investigation of the Micellar-Assisted Solubilization of Ibuprofen in Aqueous Media

Surfactants can be used to increase the solubility of poorly soluble drugs in water and to increase drug bioavailability. In this article, the aqueous solubilization of the nonsteroidal, antiinflammatory drug ibuprofen is studied experimentally and theoretically in micellar solutions of anionic (sodium dodecyl sulfate, SDS), cationic (dodecyltrimethylammonium bromide, DTAB), and nonionic (dodecyl octa(ethylene oxide), C12E8) surfactants possessing the same hydrocarbon “tail” length but differing in their hydrophilic headgroups. We find that, for these three surfactants, the aqueous solubility of ibuprofen increases linearly with increasing surfactant concentration. In particular, we observed a 16-fold increase in the solubility of ibuprofen relative to that in the aqueous buffer upon the addition of 80 mM DTAB and 80 mM C12E8 but only a 5.5-fold solubility increase upon the addition of 80 mM SDS. The highest value of the molar solubilization capacity (χ) was obtained for DTAB (χ = 0.97), followed by C12E8...
Crowding and hydrodynamic interactions likely dominate in vivo macromolecular motion

To begin to elucidate the principles of intermolecular dynamics in the crowded environment of cells, employing Brownian dynamics (BD) simulations, we examined possible mechanism(s) responsible for the great reduction in diffusion constants of macromolecules in vivo from that at infinite dilution. In an Escherichia coli cytoplasm model comprised of 15 different macromolecule types at physiological concentrations, BD simulations of molecular-shaped and equivalent sphere representations were performed with a soft repulsive potential. At cellular concentrations, the calculated diffusion constant of GFP is much larger than experiment, with no significant shape dependence. Next, using the equivalent sphere system, hydrodynamic interactions (HI) were considered. Without adjustable parameters, the in vivo experimental GFP diffusion constant was reproduced. Finally, the effects of nonspecific attractive interactions were examined. The reduction in diffusivity is very sensitive to macromolecular radius with the motion of the largest macromolecules dramatically slowed down; this is not seen if HI dominate. In addition, long-lived clusters involving the largest macromolecules form if attractions dominate, whereas HI give rise to significant, size independent intermolecular dynamic correlations. These qualitative differences provide a testable means of differentiating the importance of HI vs. nonspecific attractive interactions on macromolecular motion in cells.
Contact laws for cemented grains: Implications for grain and cement failure

Analytical solutions are presented to predict the intergranular contact load transfer in cemented granular media where both grain material and cement are elastic. The grains can be separated, have a direct point contact, or be compacted prior to cement deposition. For all these cases contact stress distributions are obtained for normal, tangential and torsional deformation of two cemented deformable grains. An important result is that intergranular cement, even if very soft, is load-bearing. Thus cementation reduces contact stress concentration (as compared with direct Hertzian interaction). Contact stresses are maximum near the center of the contact region when the cement is soft relative to the grains, and are maximum at the periphery of the contact region when the cement is stiff. These results allow us to predict the following modes of static and dynamic failure of the grains and intergranular bonds in a particulate material. (1) Uncemented grains will tend to shatter whereas cemented grains will stay intact, and the cement will fail. (This conclusion is supported by hydrostatic loading experiments where intensive crushing of uncemented glass beads was observed at about 50 MPa, whereas grains cemented at their contacts with small amounts of epoxy stayed intact.) (2) Where intergranular cementation is present, grain failure may still be expected if the cement is strong and stiff. In this case, grain damage will be initiated at the periphery of the cement layer. (3) Yielding of a cement material that is soft (as compared with the grain material) will initiate at the center of the contact region, whereas stiff cement will yield at the periphery.
Simplified Single Channel High-Speed Polarization Sensitive Retinal SDOCT

Polarization sensitive OCT (PSOCT) provides additional contrast for retinal imaging .We have constructed and tested a compact, single channel and single camera, high-speed (17,000 A-scans/sec) polarization sensitive SDOCT (PS-SDOCT) system for retinal imaging.
Methane production by deuterium impact at carbon surfaces

Abstract Molecular dynamics simulations have been performed of the sputtering of both deuterated amorphous carbon and graphite surfaces by D2 molecules at impact energies ranging from 7.5 to 30 eV/D. These simulations were done under conditions that replicate, as closely as possible, prior experimental investigations of D 2 + impacts on ATJ graphite. The substrate structure is heavily modified by cumulative impacts, and the sputtering yields change with increasing fluence. For the graphite sample, the surface continues to evolve up to the highest fluences studied, 3.8 × 1020 D/m2. For the deuterated amorphous carbon surface, however, the sample reaches a steady state at fluences of less than 1 × 1020 D/m2, at which point the structure and sputtering yields change slowly, aside from statistical fluctuations. The structure of this ensemble of steady-state surfaces is examined in detail, and is highly supersaturated with deuterium, with an enrichment in sp3 carbon. The yields of the hydrocarbons sputtered from this set of surfaces show good agreement with experiment, and are significantly larger than those from the unmodified, bulk-like amorphous carbon surface, where atomic and radical species dominate. These simulations indicate that it is both feasible and necessary to perform sputtering simulations on surfaces that have been dynamically created by impacts, if meaningful comparison with experiment is desired.
Solvothermal Synthesis of High-Aspect Ratio Alloy Semiconductor Nanowires : Cd1-xZnxS, a Case Study

High-aspect ratio Cd1−xZnxS (x = 0−1) alloy semiconductor nanowires are reported here for the first time using an ethylenediamine (en)-assisted solvothermal approach. The composition of the en−water (en-w) mixed solvent plays a crucial role in determining the morphology and crystalline phase of the alloy nanowires in the middle range of x (i.e., when x approaches 0.5). A phase transformation from hexagonal to cubic was observed for the middle range of x in an en-dominated solvent (en/w, 5:1). Nanowires with hexagonal phases were formed for the entire range of x with increasing water content of the solvent system (en/w, 2:1). The aspect ratio of the nanowires was found to be dependent on the x value as well as solvent composition. Alloy nanowires exhibit photoresponse properties when illuminated under white light. The synthesis technique is modified to synthesize core−shell Cd1−xZnxS/ZnS nanowires. Enhancement in photoluminescence efficiency is observed with a ZnS shell over the alloy nanowires.
Monoclonal antibody rat 401 recognizes schwann cells in mature and developing peripheral nerve

Monoclonal antibody Rat 401 recognizes subsets of cells in the developing central and peripheral nervous systems. Previous studies have shown that in the central nervous system (CNS) Rat 401 immunoreactivity diminishes sharply with cellular differentiation. Here we have examined the time course, cellular localization, and biochemical nature of the Rat 401 antigen in the rat peripheral nerve. In contrast to the CNS, in the periphery Rat 401 immunoreactivity is maintained into adulthood. Rat 401 staining is restricted to Schwann cells in mature peripheral nerve. Myelin-related Schwann cells are intensely immunoreactive, whereas nonmyelin-related Schwann cells are weakly immunoreactive. Unlike many Schwann cell markers, Rat 401 staining is maintained in cultured Schwann cells that lack axon contact. Biochemical analyses show that the antigen recognized by Rat 401 in the peripheral nerve is identical to that in embryonic CNS. The results demonstrate that the capacity for maintained Rat 401 immunoreactivity is restricted to Schwann cells as these cells are stained in adult animals as well as in embryos. In contrast, the same antigens are lost from the CNS at an early stage of development.