cssi/SciSciGPT-SciSciNet huggingface dataset:
Selective Estrogen Receptor Modulators Differentially Regulate Alzheimer-Like Changes in Female 3xTg-AD Mice

Estrogen-based hormone therapy (HT) in postmenopausal women may reduce the risk of Alzheimer's disease (AD), although HT remains controversial. One key concern with HT is the potential of adverse outcomes such as breast and uterine cancer. A promising strategy to maximize HT benefits and minimize HT risks is the use of selective estrogen receptor modulators (SERMs) that exert tissue-specific estrogenic effects. To begin investigating the SERM approach in reducing the risk of AD, we investigated whether AD-like neuropathology in the 3xTg-AD mouse model of AD is regulated by the SERMs propylpyrazole triol (PPT) and diarylpropionitrile (DPN) that exhibit relative specificity for estrogen receptor-alpha and -beta, respectively. Consistent with our previous observations, we found that ovariectomy-induced hormone depletion in adult female 3xTg-AD mice significantly increased accumulation of beta-amyloid protein (Abeta) and decreased hippocampal-dependent behavioral performance. Treatment with 17beta-estradiol (E2) prevented the ovariectomized-induced worsening of both pathologies. PPT treatment was similar to E2 in terms of reducing Abeta accumulation in hippocampus, subiculum, and amygdala but comparatively less effective in frontal cortex. In contrast, DPN did not significantly reduce Abeta accumulation in hippocampus and subiculum, was partially effective in frontal cortex, and nearly as effective as E2 in amygdala. Furthermore, PPT but not DPN mimicked the ability of E2 to improve behavioral performance. These findings provide initial evidence of beneficial actions of SERMs in a mouse model of AD and support continued investigation of SERMs as an alternative to estrogen-based HT in reducing the risk of AD in postmenopausal women.
Influence of Magnetic Frequency on the Thermal Behaviour of Heat Transfer Equipment

This paper presents a description of the mathematical model developed to predict the natural frequency of a particular refrigerant or refrigerant mixture and magnetic field frequency using the one-dimensional fluid flow conservation equations. The results show the dependence of the Nusselt number on the Reynolds number in the presence and absence of magnetic field. However, the results also provide evidence of enhanced heat transfer and heat flux under magnetic field compared to without magnetic field. In addition, the results presented in the paper clearly provide evidence that the heat transmission has been consistently enhanced when magnetic field is applied. It also appears that heat transfer enhancement is greater at higher Nusselt numbers.
Wavelet-based restoration for scenes with smooth bases

This paper demonstrates results of wavelet-based restoration for scenes with pixel-scale features and various degrees of smoothness. The model of choice is the so-called C/D/C system model that represents the image acquisition process by accounting for system blur, for the effects of aliasing, and for additive noise. Wavelet domain modeling discretizes both the image acquisition kernel and the representations of scenes and images. In this way the image restoration problem is formulated as a discrete least squares problem in the wavelet domain. The treatment of noise is related to the singular values of the image acquisition kernel. We show that pixel-scale features can be restored exactly in the absence of noise, for various degrees of smoothness. Results are similar in the presence of noise, except for some noise- amplification and ringing artifacts that we control with an automated choice of a restoration parameter. This paper extends work in wavelet-based restoration, and builds on research in C/D/C model-based restoration.
Components, structure, biogenesis and function of the Hydra extracellular matrix in regeneration, pattern formation and cell differentiation

The body wall of Hydra is organized as an epithelial bilayer (ectoderm and endoderm) with an intervening extracellular matrix (ECM), termed mesoglea by early biologists. Morphological studies have determined that Hydra ECM is composed of two basal lamina layers positioned at the base of each epithelial layer with an intervening interstitial matrix. Molecular and biochemical analyses of Hydra ECM have established that it contains components similar to those seen in more complicated vertebrate species. These components include such macromolecules as laminin, type IV collagen, and various fibrillar collagens. These components are synthesized in a complicated manner involving cross-talk between the epithelial bilayer. Any perturbation to ECM biogenesis leads to a blockage in Hydra morphogenesis. Blockage in ECM/cell interactions in the adult polyp also leads to problems in epithelial transdifferentiation processes. In terms of biophysical parameters, Hydra ECM is highly flexible; a property that facilitates continuous movements along the organism's longitudinal and radial axis. This is in contrast to the more rigid matrices often found in vertebrates. The flexible nature of Hydra ECM can in part now be explained by the unique structure of the organism's type IV collagen and fibrillar collagens. This review will focus on Hydra ECM in regard to: 1) its general structure, 2) its molecular composition, 3) the biophysical basis for the flexible nature of Hydra's ECM, 4) the relationship of the biogenesis of Hydra ECM to regeneration of body form, and 5) the functional role of Hydra ECM during pattern formation and cell differentiation.
Heterogeneous structure in gas–solid riser flows

Recent measurements by electric capacitance tomography reveal that, under certain operating conditions, the solids concentration distribution in the dense and acceleration regimes of gas–solid riser flows exhibits a strong heterogeneous structure, with the solids concentration near the centerline much higher than that in the annular surrounding flows (except in the wall region) within the same cross-section. This core–annulus–wall heterogeneous structure, significantly different from the commonly known “core–annulus (wall)” two-zone structure in riser flows, becomes unstable with the increase in solids loading, which eventually leads to the occurrence of choking. In this study, we propose a mechanistic model to investigate the formation and distribution of these interesting heterogeneous structures in riser flows. The intrinsic mechanisms include (1) counterflow between back mixing solids and upward moving solids from entrance, (2) the radial migration of solid flow from the wall toward the centerline of riser, and (3) the nonuniform acceleration of solids across the cross-section in the dense and acceleration regimes. The model, assuming one-dimensional two-phase flow in each zone along the riser, consists of a set of coupled ordinary-differential equations developed from the conservation laws of mass, momentum, and energy of both gas and solids phases. The solving algorithm is based on the Runge-Kutta method. Our model calculations show that the commonly known “core–annulus (wall)” flow structure occurs at low solids loadings and/or high gas velocities, whereas the core–annulus–wall flow structure is formed at moderate solids loading and/or at low gas velocities. With a high solids loading at low gas velocity, severe backflow results in a solid concentration peak formed in the core, which not only causes the flow instability but also possibly triggers the choking. Model simulations are validated by direct comparisons against measurements in solids concentrations as well as in the pressure drop along the riser, which shows a fairly good agreement. © 2008 American Institute of Chemical Engineers AIChE J, 2008
On “The Holocene CO2 rise: Anthropogenic or natural?”

Because the rising carbon dioxide (C02) trend in the late Holocene differs markedly from the natural C02 drops that occurred during the three previous interglaciations, I proposed that the Holocene increase is anthropogenic [Ruddiman, 2003]. Broecker and Stocker [2006] recently proposed using the stage 11 interglaciation (the fourth one before the present) as a potentially better analog for the Holocene because low orbital eccentricity produced similar insolation trends. They aligned termination V (the deglaciation that led into stage 11) with termination I (the most recent deglaciation) and counted forward in ‘elapsed time’ (Figure la).They noted that trends in C02 and deuterium (δD) remained at full interglacial levels early in both interglaciations and on that basis concluded that the late Holocene warmth is not only natural in origin but is also likely to last thousands of years into the future.
Functional groups show distinct differences in nitrogen cycling during early stand development: implications for forest management

Nutrient acquisition of forest stands is controlled by soil resource availability and belowground production, but tree species are rarely compared in this regard. Here, we examine ecological and management implications of nitrogen (N) dynamics during early forest stand development in productive commercial tree species with narrow (Populus deltoides Bartr. and Platanus occidentalis L.) and broad (Liquidambar styraciflua L. and Pinus taeda L.) site requirements while grown with a range of nutrient and water resources. We constructed N budgets by measuring N concentration ([N]) and N content (N C ) of above- and belowground perennial and ephemeral tissues, determined N uptake (N UP ), and calculated N use efficiency (NUE). Forest stands regulated [N] within species-specific operating ranges without clear temporal or treatment patterns, thus demonstrating equilibrium between tissue [N] and biomass accumulation. Forest stand N C and N UP increased with stand development and paralleled treatment patterns of biomass accumulation, suggesting productivity is tightly linked to N UP . Inclusion of above- and belowground ephemeral tissue turnover in N UP calculations demonstrated that maximum N demand for narrow-sites adapted species exceeded 200 kg N ha−1 year−1 while demand for broad-site adapted species was below this level. NUE was species dependent but not consistently influenced by N availability, suggesting relationships between NUE and resource availability were species dependent. Based on early stand development, species with broad site adaptability are favored for woody cropping systems because they maintain high above- and belowground productivity with minimal fertilization requirements due to higher NUE than narrow site adapted species.
Performance-Energy Considerations for Shared Cache Management in a Heterogeneous Multicore Processor

Heterogeneous multicore processors that integrate CPU cores and data-parallel accelerators such as graphic processing unit (GPU) cores onto the same die raise several new issues for sharing various on-chip resources. The shared last-level cache (LLC) is one of the most important shared resources due to its impact on performance. Accesses to the shared LLC in heterogeneous multicore processors can be dominated by the GPU due to the significantly higher number of concurrent threads supported by the architecture. Under current cache management policies, the CPU applications’ share of the LLC can be significantly reduced in the presence of competing GPU applications. For many CPU applications, a reduced share of the LLC could lead to significant performance degradation. On the contrary, GPU applications can tolerate increase in memory access latency when there is sufficient thread-level parallelism (TLP). In addition to the performance challenge, introduction of diverse cores onto the same die changes the energy consumption profile and, in turn, affects the energy efficiency of the processor. In this work, we propose heterogeneous LLC management (HeLM), a novel shared LLC management policy that takes advantage of the GPU’s tolerance for memory access latency. HeLM is able to throttle GPU LLC accesses and yield LLC space to cache-sensitive CPU applications. This throttling is achieved by allowing GPU accesses to bypass the LLC when an increase in memory access latency can be tolerated. The latency tolerance of a GPU application is determined by the availability of TLP, which is measured at runtime as the average number of threads that are available for issuing. For a baseline configuration with two CPU cores and four GPU cores, modeled after existing heterogeneous processor designs, HeLM outperforms least recently used (LRU) policy by 10.4p. Additionally, HeLM also outperforms competing policies. Our evaluations show that HeLM is able to sustain performance with varying core mix. In addition to the performance benefit, bypassing also reduces total accesses to the LLC, leading to a reduction in the energy consumption of the LLC module. However, LLC bypassing has the potential to increase off-chip bandwidth utilization and DRAM energy consumption. Our experiments show that HeLM exhibits better energy efficiency by reducing the ED2 by 18p over LRU while impacting only a 7p increase in off-chip bandwidth utilization.
Spontaneous Carbonate Formation in an Amorphous, Amine-Rich, Polymeric Drug Substance: Sevelamer HCl Product Quality

Spectral differences among multiple manufacturers/lots of sevelamer HCl were observed by Fourier transform infrared spectroscopy, and further characterization was performed to identify the cause for these differences. The drug substance is a polymer that possesses a large molecular weight, is amorphous, and is practically insoluble in both water and organic solvents. Thus, solid-state characterization methods (spectroscopic and thermal) were required to identify and characterize differences among the samples to assess possible differences in product quality. ¹³C cross-polarization-magic-angle-spinning nuclear magnetic resonance spectroscopy of sevelamer HCl substances demonstrated the presence of a carbonyl-containing species, which was attributed to a carbonate impurity among samples. Stability studies demonstrated that this carbonate impurity formed spontaneously upon exposure of the drug substance to atmospheric water vapor and carbon dioxide, even under ambient conditions. Mechanistically, this behavior likely arises from the large number of primary and secondary amine groups, the hygroscopicity of the HCl salt, and a high degree of molecular mobility due to the amorphous nature of the drug substance.
Personal and Contextual Variables Related to Work Hope Among Undergraduate Students From Underrepresented Backgrounds

This study investigated the relationships among personal and environmental variables (i.e., college student generation status, psychological distress, experiences with racism and classism, and perceived social status [PSS]) and work hope. One hundred and seventy-six undergraduate students attending a predominantly White institution who identified as members of an underrepresented racial/ethnic group completed the study. Consistent with the hypotheses, results demonstrated that increased psychological distress and more experiences with classism, experiences with racism related to lowered levels of work hope and that heightened PSS related positively to work hope. When examined in combination, all variables significantly predicted work hope, but only the βs for psychological distress and PSS were significant. Unexpectedly, first-generation college students did not significantly differ from continuing generation college students in levels of work hope. Limitations, directions for future research, and implica...
Direct Imaging of Site-Specific Photocatalytical Reactions of O2 on TiO2(110)

Photostimulated reactions of single O2 molecules on reduced TiO2(110) surfaces were directly observed at an atomic level with high-resolution scanning tunneling microscopy at 50 K. Two distinct reactions of O2 desorption and dissociation occur at different active sites of terminal Ti atoms and bridging O vacancies, respectively. Two reaction channels follow very different kinetics. While hole-mediated O2 desorption is promptly and fully completed, electron-mediated O2 dissociation is much slower and is quenched above some critical O2 coverage. Evidently, the O2 photochemistry on TiO2(110) is quite more complex than thought previously. Density functional theory calculations indicate that both coordination and charge state of an O2 molecule chemisorbed at the specific site largely determine a particular reaction pathway.
Research agenda for a green economics of abundance

An economics of abundance attempts to eliminate socially constructed scarcities by addressing people's fundamental needs and by undermining the social institutions which create scarcity by manipulating supply and demand. The overarching goal is to work towards enhancing individual freedom, social equity, and environmental sustainability, which together imply wholeness or integrity. A research agenda of an economics of abundance must focus on how to construct institutional alternatives regarding property regimes and exchange systems, how to undermine monopolies by encouraging the entry of new businesses into oligopolistic markets and by enhancing individual and community-level self-reliance, how to promote non-violent conflict resolution, how to create health-promoting environments and minimise the costs of effective healthcare, how to promote relevant research and education, and how to enhance networking towards all these goals.
Collagen synthesis and degradation in acutely damaged mouse lung tissue following treatment with prednisolone.

Corticosteroids are widely used to treat patients with acute lung damage. Recent work has shown that the administration of 30 mg/kg prednisolone to mice, twice daily on days 1-5 after the induction of lung damage with butylated hydroxytoluene (BHT), results in the development of a more severe fibrotic lesion [J.P. Kehrer, A.J.P. Klein-Szanto, E. M. B. Sorensen, R. Pearlman and M. H. Rosner, Am. Rev. resp. Dis. 130, 256 (1984)]. In the present study, the rate of collagen synthesis in lung tissue from BHT-saline-treated mice was greater than that in lung tissue from oil-treated controls at all days examined. During prednisolone treatment, the rate of pulmonary collagen synthesis was significantly less in tissue from BHT-prednisolone-treated mice compared to BHT-saline controls. Two days after steroid treatment was stopped (day 7 after BHT), there was a significant increase in the rate of collagen synthesis in lung tissue from BHT-prednisolone-treated mice compared to tissue from both BHT- and oil-treated controls. This increase reached a maximum on day 11 and persisted to day 14 after BHT. The rate of pulmonary non-collagen protein synthesis was inconsistently increased in response to treatments with BHT and/or prednisolone. There was, therefore, a relatively greater increase in the synthesis of collagen. The percentage of total protein synthesis committed to collagen increased from 2% in oil-treated controls to 5% on day 7 after BHT alone and reached a maximum of 7.1% on day 11 in lung tissue from BHT-prednisolone-treated mice. The percentage of newly synthesized collagen that was degraded in lung tissue from BHT-prednisolone-treated mice was significantly lower than BHT-saline on days 7 and 11, and lower than oil-prednisolone on day 14. These results show that collagen synthesis was decreased in BHT-damaged mouse lung tissue during short-term, high-dose steroid therapy. There was, however, an increase in collagen synthesis and a decrease in the degradation of newly synthesized collagen after steroid therapy was stopped. These changes in collagen metabolism may contribute to the steroid-induced enhancement of fibrosis seen in BHT-treated mice.
α- and β-curves, sister-sister and mother-daughter correlations in cell population dynamics

Abstract The α- and β-curves and sister-sister and mother-daughter cycle length correlations are analyzed for a general model of age and size structured cell population dynamics. Some basic facts concerning these concepts are established. A criterion is given for log α ( a ) and log β ( a ) to have asymptotically equal slopes. The significance of size dependence upon sister-sister and mother-daughter correlations is demonstrated. Some numerical examples are given to illustrate the concepts.
Recent developments in assessing microstructure-sensitive early stage fatigue of polycrystals

Abstract Fatigue failure is a leading concern for many applications involving structures for transportation, manufacturing, medical devices, and electronic components. Recent advances in modeling and simulation, coupled with in situ experimental techniques, have enhanced the understanding required to distinguish and characterize mechanisms of fatigue crack formation and early growth at scales of underlying microstructure. In particular, microstructure substantially influences high cycle fatigue resistance and contributes to variability of the fatigue response. This paper reviews the confluence of recent experimental and modeling advances aimed at understanding and modeling of the formation and early growth of fatigue cracks with size on the order of dominant microstructure attributes.
Challenges, obligations, and pending career interruptions: Securing meanings at the exit stage of sport mega-event work

Abstract Work for sport mega-events is shaped by the unique characteristics of the event organizing committee as it is temporary, often bureaucratic, grows rapidly, and provides rich symbolism. This study provides a follow-up to Xing and Chalip's study examining the experience of work at the Beijing Organizing Committee for the Olympic Games (BOCOG), which took place 2 years prior to the Games. Participant observation and interviews with the original study participants were conducted immediately prior to the Games. The themes obtained 2 years earlier had evolved. Three new themes emerged capturing the evolution of the work experience from the event's planning to implementation: the workers faced more challenges; they felt impelled to do a good job throughout; and they were disturbed by the post-Games job uncertainty. Meanwhile, the immediate work environment continued to provide supports. The significance of the work was seen in the values of the Games to the country and a better understanding of Chinese ...
Consistent approximation of an optimal search problem

This paper focuses on the problem of optimizing the trajectories of multiple searchers attempting to detect a non-evading moving target whose motion is conditionally deterministic. This problem is a parameter-distributed optimal control problem, as it involves an integration over a space of stochastic parameters as well as an integration over the time domain. In this paper, we consider a wide range of discretization schemes to approximate the integral in the parameter space by a finite summation, which results in a standard control-constrained optimal control problem that can be solved using existing techniques in optimal control theory. We prove that when the sequence of solutions to the discretized problem has an accumulation point, it is guaranteed to be an optimal solution of the original search problem. We also provide a necessary condition that accumulation points of this sequence must satisfy.
Endogenous alcoholic fermentation in yeast induced by 2, 4-dinitrophenol.

Abstract 1. 1. Although well-starved yeast, under anaerobic conditions, in the absence of external substrate, produces no readily measurable quantity of CO2, the addition of appropriate concentrations of 2, 4-dinitrophenol (DNP) or of azide can induce an appreciable CO2 production. 2. 2. The DNP-induced CO2 production is associated with the production of ethyl alcohol, which was specifically identified by the melting point of its p-nitrobenzoyl derivative. At least one-half equivalent of alcohol was recovered for each equivalent of CO2 produced. 3. 3. At least one-third of the substrate for the DNP-induced fermentation is glycogen. Almost one-half is acid-hydrolyzable, reducible, carbohydrate reserve. 4. 4. It is concluded that glycogen can be made available as a substrate for alcoholic fermentation, by the action of DNP or azide on an “uncoupling mechanism” which, in the normal cell, prevents the fermentation of glycogen.
Leukocyte concentrations in discrimination of benign from malignant lung lesions

Malignant lung lesions are associated with significant changes in leukocyte concentrations. However, overlap of values between normal subjects and patients with cancer has limited the clinical utility of this determination. To decrease the overlap, 2,000 cells per differential determination were counted, and replicate automated cell counts were performed in blood samples obtained on different mornings between 7 and 9 A.M. Seventy-five patients who presented with undiagnosed lung lesions were analyzed. Benign and malignant lung lesions could be accurately distinguished by either relative granulocyte or lymphocyte counts. With 65.5 percent granulocytes as the cutoff, 86 percent of patients (38 of 44) proved to have lung cancer had higher values, and 97 percent of patients (30 of 31) with benign lesions had lower values. Likewise, with 28 percent lymphocytes as the cutoff, 87 percent of patients with lung cancer (39 of 44) had lower values, and 94 percent of patients (29 of 31) with benign disease had higher values. Relative monocyte counts were not different. Absolute leukocyte concentrations, although different for each group, had considerable overlap and thus were poor discriminators. These data suggest that precise analytical techniques and the use of relative leukocyte concentrations can improve the clinical utility of the leukocyte count as a discriminator of benign and malignant lung lesions.
Deprivation of protein or amino acid induces C/EBPβ synthesis and binding to amino acid response elements, but its action is not an absolute requirement for enhanced transcription

A nutrient stress signalling pathway is triggered in response to protein or amino acid deprivation, namely the AAR (amino acid response), and previous studies have shown that C/EBPβ (CCAAT/enhancer-binding protein β) expression is up-regulated following activation of the AAR. DNA-binding studies, both in vitro and in vivo, have revealed increased C/EBPβ association with AARE (AAR element) sequences in AAR target genes, but its role is still unresolved. The present results show that in HepG2 human hepatoma cells, the total amount of C/EBPβ protein, both the activating [LAP* and LAP (liver-enriched activating protein)] and inhibitory [LIP (liver-enriched inhibitory)] isoforms, was increased in histidine-deprived cells. Immunoblotting of subcellular fractions and immunostaining revealed that most of the C/EBPβ was located in the nucleus. Consistent with these observations, amino acid limitation caused an increase in C/EBPβ DNA-binding activity in nuclear extracts and chromatin immunoprecipitation revealed an increase in C/EBPβ binding to the AARE region in vivo, but at a time when transcription from the target gene was declining. A constant fraction of the basal and increased C/EBPβ protein was phosphorylated on Thr235 and the phospho-C/EBPβ did bind to an AARE. Induction of AARE-enhanced transcription was slightly greater in C/EBPβ-deficient MEFs (mouse embryonic fibroblasts) or C/EBPβ siRNA (small interfering RNA)-treated HepG2 cells compared with the corresponding control cells. Transient expression of LAP*, LAP or LIP in C/EBPβ-deficient fibroblasts caused suppression of increased transcription from an AARE-driven reporter gene. Collectively, the results demonstrate that C/EBPβ is not required for transcriptional activation by the AAR pathway but, when present, acts in concert with ATF3 (activating transcription factor 3) to suppress transcription during the latter stages of the response.
Restoring Public Confidence in American Business

American business leaders have hurt public confidence in the private enterprise system. Without sustained changes in the way corporations, including top management, conduct business, a new round of pervasive, arbitrary government regulation will ensue.
Temperature compensation of piezoresistive pressure sensors

Abstract A major problem associated with piezoresistive pressure sensors is their cross sensitivity to temperature. The influence of temperature is manifested as a change in the span and offset of the sensor output. Moreover, in batch fabrication, minor process variations change the temperature characteristics for individual units. In this paper, a simulation model for the batch fabrication of piezoresistive pressure sensors is presented. An error band for the sensor response is determined in terms of processing variations for a temperature range of −40 to 130 °C over a pressure range of 0 to 45 psi. Utilizing this information, a new temperature-compensation technique, especially suited for batch fabrication, is described. This technique shows very encouraging results in removing the zero pressure offset and significantly reduces the errors caused by processing variations on the same wafer.
WHY IS JAPAN NEOLIBERALIZING? RESCALING OF THE JAPANESE DEVELOPMENTAL STATE AND IDEOLOGY OF STATE–CAPITAL FIXING

This study examines Japan’s state spatial restructuring to explore the reasons behind it. By doing so, it investigates the grounds on which Japan is adopting neoliberalism. Since the early 2000s, J...
Novel Low Reynolds Number Mixers for Microfluidic Applications

We present two new designs of compact mixers that can provide good mixing at low Reynolds numbers encountered in many microfluidic devices. The new designs benefit from curvature induced cross-stream vortices to enhance mixing of two co-flowing streams of fluids arranged side by side. One of the designs is a spiral of rectangular cross-section, while the other is a series of concentric circular channels arranged as a labyrinth. Both utilize the formation of sustained secondary flows to enhance mixing between two streams. Currently, the devices are fabricated in aluminum using standard machining techniques. However, they can be reduced further in size using standard microfabrication techniques. Mixing experiments were conducted in these channels at a Reynolds number of 6.8 using two sucrose solutions, one of which was laced with Rhodamine 6G dye. Compared to a experiment in an equivalent straight channel, a significant enhancement in the mixing of the two streams, as indicated by the intensity of the second fluid’s color, was observed. The present designs provide a compact and easy-to-fabricate alternative to various other concepts proposed in literature.Copyright © 2003 by ASME
Biotin Reagents in Antibody Pretargeting. 6. Synthesis and in Vivo Evaluation of Astatinated and Radioiodinated Aryl- and nido-Carboranyl-biotin Derivatives

An investigation has been conducted to prepare and evaluate several radiohalogenated biotin derivatives as part of our studies to develop reagents for carrying 2 1 1 At in cancer pretargeting protocols. The primary goal of the investigation was to determine the in vivo stability and distribution properties of astatinated biotin derivatives. In addition to astatination, the biotin derivatives were radioiodinated for in vitro and in vivo comparison. Biodistributions were conducted in athymic mice, with sacrifice times of 1, 4, and 24 h to correspond to 9%, 32%, and 90% of 2 1 1 At decay (t 1 / 2 = 7.21 h). In the investigation, two biotin derivatives, la and 2a, were synthesized which had structures that contain a biotin moiety, a biotinidase-blocking moiety, an ether linker moiety, and an aryl stannane moiety for radiohalogenation. Biotin derivatives 1a and 2a were radiolabeled with 1 2 5 / 1 3 1 I to give [ 1 2 5 / 1 3 1 I]1b or [ 1 2 5 I]2b and with 2 1 1 At to give [ 2 1 1 At]1c or [ 2 1 1 At] 2 c . In vivo studies demonstrated that co-injected [ 1 2 5 I]2b and [ 1 3 1 I]1b had very similar tissue distributions in athymic mice. Co-injection of [ 2 1 1 At]2c and [ 1 2 5 I]2b provided data that indicated that rapid deastatination occurred in vivo. A second set of biotin derivatives, 3a, 4a, and 5a, were synthesized which had structures that contain a biotin moiety, a biotinidase-blocking moiety, and an anionic nido-carborane moiety for radiohalogenation. The biotin derivatives 4a and 5a contained an aryl moiety not present in 3a, and 5a had a trialkylamine functionality not present in 3a or 4a. Biotin derivative 3a was radioiodinated, but was not further investigated. Biotin derivatives 4a and 5a were radiolabeled with 2 1 1 At and 1 2 5 I to produce [ 1 2 5 I]4b/ [ 2 1 1 At]4c and [ 1 2 5 I]5b/[ 2 1 1 At]5c. Comparison of [ 1 2 5 I]4b and (separately) [ 1 2 5 I]5b with [ 1 3 1 I]1b showed that the nido-carborane containing biotin derivatives were retained in blood and tissue more than the aryl iodide derivative. In vivo evaluations of [ 2 1 1 At]4c/[ 1 2 5 I]4b and (separately) [ 2 1 1 At]5c/[ 1 2 5 I]5b indicated that some deastatination occurred in these compounds, but it was much less than observed for the aryl derivative [ 2 1 1 At]2c. While the nido-carborane containing biotin derivatives provide a significant improvement in astatine stability over biotin derivatives previously studied, additional derivatives need to be prepared and studied to further improve the in vivo stability and blood/tissue clearance of these compounds.
On the thermodynamics of adsorption at interfaces as it influences decohesion

Earlier computations on the work of separation of boundaries with adsorbed solute atmospheres are reconsidered in terms of reversible work cycles. Special attention is given to two limiting cases. These are the separation of a material interface under fully equilibrated conditions, for which the chemical potential of the adsorbed solute remains constant, and separation under constrained conditions for which the surface excess solute concentration remains constant (i.e., the same on the two newly created free surfaces as present initially on the unstressed interface). The results are consistent with the limiting cases treated before and include the extension to more general cases of solute interactions, including multi-component systems. The work terms are conveniently represented on diagrams of chemical potentialvs surface excess solute concentration. A general separation process is then represented as a path in this diagram which begins on the adsorption isotherm for the unstressed interface and ends on the adsorption isotherm for the pair of newly created surfaces.
An integrated modeling framework for infrastructure system-of-systems simulation

Design of future hard infrastructure must consider emergent behaviors from cross-system interdependencies. Understanding these interdependencies is challenging due to high levels of integration in high-performance systems and their operation as a collaborative system-of-systems managed by multiple organizations. Existing modeling frameworks have limitations for strategic planning either because important spatial structure attributes have been abstracted out or behavioral models are oriented to shorter-term analysis with a static network structure. This paper presents a formal modeling framework as a first step to integrating infrastructure system models in a system-of-systems simulation addressing these concerns. First, a graph-theoretic structural framework captures the spatial dimension of physical infrastructure. An element's simulation state includes location, parent, resource contents, and operational state properties. Second, a functional behavioral framework captures the temporal dimension of infrastructure operations at a level suitable for strategic analysis. Resource behaviors determine the flow of resources into or out of nodes and element behaviors modify other state including the network structure. Two application use cases illustrate the usefulness of the modeling framework in varying contexts. The first case applies the framework to future space exploration infrastructure with an emphasis on mobile system elements and discrete resource flows. The second case applies the framework to infrastructure investment in Saudi Arabia with an emphasis on immobile system elements aggregated at the city level and continuous resource flows. Finally, conclusions present future work planned for implementing the framework in a simulation software tool.
Maximin Justice, Sacrifice, and the Reciprocity Argument: A Pragmatic Reassessment of the Rawls/Nozick Debate

Theories of economic justice are characteristically based on abstract ethical concerns often unrelated to practical distributive results. Two decades ago, Rawls's theory of justice began as a reaction against the alleged ‘sacrifices’ condoned by utilitarian theory. One variant of this objection is that utilitarianism permits gross inequalities, severe deprivations of individual liberty, or even the enslavement of society's least well-off individuals. There are, however, more subtle forms of the objection. In Rawls, it is often waged without any claim that utilitarianism does in fact imply such gross deprivations in actual realworld circumstances. A second variant hinges, rather, on the milder claim that utilitarianism could condone such deprivations or sacrifices in some possible world—the objection being that utilitarianism improperly makes justice contingent, or uncertain, in this way. A third, still more abstract, variant would be that utilitarianism is flawed—not because of any practical distributive result, actual or hypothetical, but in theory—due to the way it treats individuals' interests, or the ‘concept of persons’ it presupposes.
Anti-inflammatory and neuroprotective effects of an orally active apocynin derivative in pre-clinical models of Parkinson's disease.

Parkinson’s disease (PD) is a devastating neurodegenerative disorder characterized by progressive motor debilitation, which affects several million people worldwide. Recent evidence suggests that glial cell activation and its inflammatory response may contribute to the progressive degeneration of dopaminergic neurons in PD. Currently, there are no neuroprotective agents available that can effectively slow the disease progression. Herein, we evaluated the anti-inflammatory and antioxidant efficacy of diapocynin, an oxidative metabolite of the naturally occurring agent apocynin, in a pre-clinical 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Both pre-treatment and post-treatment of diapocynin were tested in the MPTP mouse model of PD. Diapocynin was administered via oral gavage to MPTP-treated mice. Following the treatment, behavioral, neurochemical and immunohistological studies were performed. Neuroinflammatory markers, such as ionized calcium binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), gp91phox and inducible nitric oxide synthase (iNOS), were measured in the nigrostriatal system. Nigral tyrosine hydroxylase (TH)-positive neurons as well as oxidative markers 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE) and striatal dopamine levels were quantified for assessment of the neuroprotective efficacy of diapocynin. Oral administration of diapocynin significantly attenuated MPTP-induced microglial and astroglial cell activation in the substantia nigra (SN). MPTP-induced expression of gp91phox and iNOS activation in the glial cells of SN was also completely blocked by diapocynin. Notably, diapocynin markedly inhibited MPTP-induced oxidative markers including 3-NT and 4-HNE levels in the SN. Treatment with diapocynin also significantly improved locomotor activity, restored dopamine and its metabolites, and protected dopaminergic neurons and their nerve terminals in this pre-clinical model of PD. Importantly, diapocynin administered 3 days after initiation of the disease restored the neurochemical deficits. Diapocynin also halted the disease progression in a chronic mouse model of PD. Collectively, these results demonstrate that diapocynin exhibits profound neuroprotective effects in a pre-clinical animal model of PD by attenuating oxidative damage and neuroinflammatory responses. These findings may have important translational implications for treating PD patients.
Multiscale Agent-based Model of Tumor Angiogenesis

Computational models of cancer complement the biological study of tumor growth. However, existing modeling approaches can be both inefficient and inaccurate due to the difficulties of representing the complex interactions between cells and tissues. We present a three-dimensional multiscale agent-based model of tumor growth with angiogenesis. The model is designed to easily adapt to various cancer types, although we focus on breast cancer. It includes cellular (genetic control), tissue (cells, blood vessels, angiogenesis), and molecular (VEGF, diffusion) levels of representation. Unlike in most cancer models, both normally functioning tissue cells and tumor cells are included in the model. Tumors grow following the expected spheroid cluster pattern, with growth limited by available oxygen. Angiogenesis, the process by which tumors may encourage new vessel growth for nutrient diffusion, is modeled with a new discrete approach that we propose will decrease computational cost. Our results show that despite proposing these new abstractions, we see similar results to previously accepted angiogenesis models. This may indicate that a more discrete approach should be considered by modelers in the future.
The Structural Determinants of Democratic Consolidation: Evidence from the Third World

Democratic consolidation is the process by which a newly established democratic regime becomes sufficiently durable that a return to nondemocratic rule is no longer likely. The authors examine a wi...
A Stochastic Approach to Measuring the Robustness of Resource Allocations in Distributed Systems

Often, parallel and distributed computing systems must operate in an environment replete with uncertainty. Determining a resource allocation that accounts for this uncertainty in a way that can provide a probabilistic guarantee that a given level of quality of service (QoS) is achieved is an important research problem. This paper defines a stochastic methodology for quantifiably determining a resource allocation?s ability to satisfy QoS constraints in the midst of uncertainty in system parameters. Uncertainty in system parameters and its impact on system performance are modeled stochastically. This stochastic model is then used to derive a quantitative expression for the robustness of a resource allocation. The paper investigates the utility of the proposed stochastic robustness metric by applying the metric to resource allocations in a simulated distributed system. The simulation results are then compared with deterministically defined metrics from the literature.
Delay-limited throughput maximization for fading channels using rate and power control

The fading channels seen in many wireless systems provide a particularly hostile environment for reliable communication. Current metrics for evaluating the performance limits of fading channels have shortcomings. Ergodic capacity, representing the ultimate error-free communications limit, only applies to systems with infinite coding delay. Practical systems are delay-limited and must use finite-length codes. For delay-limited systems /spl epsi/-capacity and delay-limited capacity are typically used to quantify the communications performance. However, /spl epsi/-capacity is not an estimate of error-free performance while delay-limited capacity tends to be an overly conservative measure. We model practical systems as a single server queue and quantify the communications performance as the average throughput through the queue. Throughput is maximized by optimally selecting the transmission rate and power control strategy. Using this approach we arrive at striking conclusions. First, we show that a throughput very close to ergodic capacity can be achieved with a small coding delay. Second, the optimal transmission rate for some systems can be higher than the ergodic capacity of the channel. Third, we demonstrate the notion that power adaptation does not improve communication performance does not hold for delay-limited systems.
Experimental infection of pregnant goats with bovine viral diarrhea virus (BVDV) 1 or 2

Infections with bovine viral diarrhea virus (BVDV) of the genus pestivirus, family Flaviviridae, are not limited to cattle but occur in various artiodactyls. Persistently infected (PI) cattle are the main source of BVDV. Persistent infections also occur in heterologous hosts such as sheep and deer. BVDV infections of goats commonly result in reproductive disease, but viable PI goats are rare. Using 2 BVDV isolates, previously demonstrated to cause PI cattle and white-tailed deer, this study evaluated the outcome of experimental infection of pregnant goats. Pregnant goats (5 goats/group) were intranasally inoculated with BVDV 1b AU526 (group 1) or BVDV 2 PA131 (group 2) at approximately 25–35 days of gestation. The outcome of infection varied considerably between groups. In group 1, only 3 does became viremic, and 1 doe gave birth to a stillborn fetus and a viable PI kid, which appeared healthy and shed BVDV continuously. In group 2, all does became viremic, 4/5 does aborted, and 1 doe gave birth to a non-viable PI kid. Immunohistochemistry demonstrated BVDV antigen in tissues of evaluated fetuses, with similar distribution but reduced intensity as compared to cattle. The genetic sequence of inoculated viruses was compared to those from PI kids and their dam. Most nucleotide changes in group 1 were present during the dam’s acute infection. In group 2, a similar number of mutations resulted from fetal infection as from maternal acute infection. Results demonstrated that BVDV may cause reproductive disease but may also be maintained in goats.
nanoProtean: scalable system software for a gigabit active router

We introduce nanoProtean, a new router operating system and execution environment that reduces system overhead, making it possible to process the packets produced by gigabit networks. The ovearhead decreases as the offered load per packet increases due to the following features in nanoProtean (i) a completely preemptable operating system, (ii) efficient management of the system's job queue, and (iii) system support for fine-grain sharing of processing time amongst packets. These features are a result of a novel integration of efficient thread scheduling for multiprocessors and interrupt handling. Experimental analysis used to test our systems scalability uses a technique to emulate processing requests generated in real-time at 802.3z (gigabit) line speeds and greater. Our results demonstrate 2 Gbps routing; with MAE-East tables on two processors, and system overheads decreasing from 3.6 /spl mu/s per packet to 1.64 /spl mu/s per packet on one processor. By reducing the system overhead, we also demonstrate that nanoProtean enables active networking in a router supporting gigabit connections.
Ascorbic Acid Nutritional Status Does Not Affect the Biochemical Response to Paraquat

Guinea pigs were subjected to dietary control of ascorbic acid intake to produce deficient, normal, and supplemented tissue ascorbate concentrations. Paraquat, a potent pulmonary toxin, was then administered. Tissue distribution and covalent binding of paraquat were not affected significantly by ascorbate nutritional status except for decreased 24-hr kidney burdens in deficient animals. Paraquat increased pulmonary thiobarbituric acid reactivity and mixed disulfide formation, but no evidence of either a protective or a potentiative interaction of endogenous ascorbate and paraquat was observed. This study indicates that alteration of endogenous ascorbic acid levels does not alter the biochemical response to paraquat.
Algebraic differential equations and rational control systems

An equivalence is shown between realizability of input/output (i/o) operators by rational control systems and high-order algebraic differential equations for (i/o) pairs. This generalizes, to nonli...