cssi/SciSciGPT-SciSciNet huggingface dataset:
Improving Cardiovascular Drug and Device Development and Evidence Through Patient-Centered Research and Clinical Trials: A Call to Action From the Value in Healthcare Initiative's Partnering With Regulators Learning Collaborative

The pipeline of new cardiovascular drugs is relatively limited compared with many other clinical areas. Challenges causing lagging drug innovation include the duration and expense of cardiovascular clinical trials needed for regulatory evaluation and approvals, which generally must demonstrate noninferiority to existing standards of care and measure longer-term outcomes. By comparison, there has been substantial progress in cardiovascular device innovation. There has also been progress in cardiovascular trial participation equity in recent years, especially among women, due in part to important efforts by Food and Drug Administration, National Institutes of Health, American Heart Association, and others. Yet women and especially racial and ethnic minority populations remain underrepresented in cardiovascular trials, indicating much work ahead to continue recent success. Given these challenges and opportunities, the multistakeholder Partnering with Regulators Learning Collaborative of the Value in Healthcare Initiative, a collaboration of the American Heart Association and the Robert J. Margolis, MD, Center for Health Policy at Duke University, identified how to improve the evidence generation process for cardiovascular drugs and devices. Drawing on a series of meetings, literature reviews, and analyses of regulatory options, the Collaborative makes recommendations across four identified areas for improvement. First, we offer strategies to enhance patient engagement in trial design, convenient participation, and meaningful end points and outcomes to improve patient recruitment and retention (major expenses in clinical trials). Second, new digital technologies expand the potential for real-world evidence to streamline data collection and reduce cost and time of trials. However, technical challenges must be overcome to routinely leverage real-world data, including standardizing data, managing data quality, understanding data comparability, and ensuring real-world evidence does not worsen inequities. Third, as trials are driven by evidence needs of regulators and payers, we recommend ways to improve their collaboration in trial design to streamline and standardize efficient and innovative trials, reducing costs and delays. Finally, we discuss creative ways to expand the minuscule proportion of sites involved in cardiovascular evidence generation and medical product development. These actions, paired with continued policy research into better ways to pay for and equitably develop therapies, will help reduce the cost and complexity of drug and device research, development, and trials.
Mechanical Purcell filters for microwave quantum machines

In circuit quantum electrodynamics, measuring the state of a superconducting qubit introduces a loss channel, which can enhance spontaneous emission through the Purcell effect, thus decreasing the qubit lifetime. This decay can be mitigated by performing the measurement through a Purcell filter, which strongly suppresses signal propagation at the qubit transition frequency. If the filter is also well-matched at the readout cavity frequency, it will protect the qubit from decoherence channels without sacrificing measurement bandwidth. We propose and analyze design for a mechanical Purcell filter, which we also fabricate and characterize at room temperature. The filter is composed of an array of nanomechanical resonators in thin-film lithium niobate, connected in a ladder topology, with series and parallel resonances arranged to produce a bandpass response. Their modest footprint, steep band edges, and lack of cross talk make these filters an appealing alternative to analogous electromagnetic versions currently used in microwave quantum machines.In circuit quantum electrodynamics, measuring the state of a superconducting qubit introduces a loss channel, which can enhance spontaneous emission through the Purcell effect, thus decreasing the qubit lifetime. This decay can be mitigated by performing the measurement through a Purcell filter, which strongly suppresses signal propagation at the qubit transition frequency. If the filter is also well-matched at the readout cavity frequency, it will protect the qubit from decoherence channels without sacrificing measurement bandwidth. We propose and analyze design for a mechanical Purcell filter, which we also fabricate and characterize at room temperature. The filter is composed of an array of nanomechanical resonators in thin-film lithium niobate, connected in a ladder topology, with series and parallel resonances arranged to produce a bandpass response. Their modest footprint, steep band edges, and lack of cross talk make these filters an appealing alternative to analogous electromagnetic versions curre...
A framework for interdisciplinary research in food systems

Global food systems have complex, diverse and coupled multisectoral dynamics that present challenges for progressive interdisciplinary research. We propose a framework for inclusive, flexible and iterative integration across disciplines to support the entire research process.
Neural Network Training Using &#120001; 1 -Regularization and Bi-fidelity Data.

With the capability of accurately representing a functional relationship between the inputs of a physical system's model and output quantities of interest, neural networks have become popular for surrogate modeling in scientific applications. However, as these networks are over-parameterized, their training often requires a large amount of data. To prevent overfitting and improve generalization error, regularization based on, e.g., $\ell_1$- and $\ell_2$-norms of the parameters is applied. Similarly, multiple connections of the network may be pruned to increase sparsity in the network parameters. In this paper, we explore the effects of sparsity promoting $\ell_1$-regularization on training neural networks when only a small training dataset from a high-fidelity model is available. As opposed to standard $\ell_1$-regularization that is known to be inadequate, we consider two variants of $\ell_1$-regularization informed by the parameters of an identical network trained using data from lower-fidelity models of the problem at hand. These bi-fidelity strategies are generalizations of transfer learning of neural networks that uses the parameters learned from a large low-fidelity dataset to efficiently train networks for a small high-fidelity dataset. We also compare the bi-fidelity strategies with two $\ell_1$-regularization methods that only use the high-fidelity dataset. Three numerical examples for propagating uncertainty through physical systems are used to show that the proposed bi-fidelity $\ell_1$-regularization strategies produce errors that are one order of magnitude smaller than those of networks trained only using datasets from the high-fidelity models.
Repression of ZCT1, ZCT2 and ZCT3 affects expression of terpenoid indole alkaloid biosynthetic and regulatory genes

Terpenoid indole alkaloids (TIAs) include several valuable pharmaceuticals. As Catharanthus roseus remains the primary source of these TIA pharmaceuticals, several research groups have devoted substantial efforts to increase production of these compounds by C. roseus. Efforts to increase TIA production by overexpressing positive regulators of TIA biosynthetic genes have met with limited success. This limited success might be due to the fact that overexpression of several positive TIA regulators turns on expression of negative regulators of TIA biosynthetic genes. Consequently, a more effective approach for increasing expression of TIA biosynthetic genes might be to decrease expression of negative regulators of TIA biosynthetic genes. Towards this end, an RNAi construct was generated that expresses a hairpin RNA carrying nucleotide fragments from three negative transcriptional regulators of TIA genes, ZCT1, ZCT2 and ZCT3, under the control of a beta-estradiol inducible promoter. Transgenic C. roseus hairy root lines carrying this ZCT RNAi construct exhibit significant reductions in transcript levels of all three ZCT genes. Surprisingly, out of eight TIA biosynthetic genes analyzed, seven (CPR, LAMT, TDC, STR, 16OMT, D4H and DAT) exhibited decreased rather than increased transcript levels in response to reductions in ZCT transcript levels. The lone exception was T19H, which exhibited the expected negative correlation in transcript levels with transcript levels of all three ZCT genes. A possible explanation for the T19H expression pattern being the opposite of the expression patterns of the other TIA biosynthetic genes tested is that T19H shunts metabolites away from vindoline production whereas the products of the other genes tested shunt metabolites towards vindoline metabolism. Consequently, both increased expression of T19H and decreased expression of one or more of the other seven genes tested would be expected to have similar effects on flux through the TIA pathway. As T19H expression is lower in the ZCT RNAi hairy root lines than in the control hairy root line, the ZCTs could act directly to inhibit expression of T19H. In contrast, ZCT regulation of the other seven TIA biosynthetic genes tested is likely to occur indirectly, possibly by the ZCTs turning off expression of a negative transcriptional regulator of some TIA genes. In fact, transcript levels of a negative TIA transcriptional regulator, GBF1, exhibited a strong, and statistically significant, negative correlation with transcript levels of ZCT1, ZCT2 and ZCT3. Together, these findings suggest that the ZCTs repress expression of some TIA biosynthetic genes, but increase expression of other TIA biosynthetic genes, possibly by turning down expression of GBF1.
Inflammatory cytokines associated with outcomes in orthopedic trauma patients independent of New Injury Severity score: A pilot prospective cohort study.

Traumatic injury is the leading cause of mortality in patients under 50. It is associated with a complex inflammatory response involving hormonal, immunologic, and metabolic mediators. The marked elevation of cytokines and inflammatory mediators subsequently correlates with the development of posttraumatic complications. The aim was to determine whether elevated cytokine levels provide a predictive value for orthopedic trauma patients. A prospective cohort study of patients with New Injury Severity Score (NISS) > 5 was undertaken. IL-6, IL-8, IL-10, and migration inhibitory factor levels were measured within 24-h of presentation. Demographic covariates and clinical outcomes were obtained from the medical records. Fifty-eight patients (83% male, 40 years) were included. Addition of IL-6 to baseline models significantly improved prediction of pulmonary complication (LR = 6.21, p = 0.01), ICU (change in R2 = 0.31, p < 0.01), and hospital length of stay (change in R2 = 0.16, p < 0.01). The addition of IL-8 significantly improved the prediction of acute kidney injury (LR = 9.15, p < 0.01). The addition of postinjury IL-6 level to baseline New Injury Severity Score model is better able to predict the occurrence of pulmonary complications as well as prolonged ICU and hospital length of stay.
An Introduction to Africana Philosophy

Introduction: Africana philosophy in context Part I. Groundings: 1. Africana philosophy as a modern philosophy 2. Classic eighteenth- and nineteenth-century foundations Part II. From New World to New Worlds: 3. Three pillars of African-American philosophy 4. Africana philosophical movements in the United States, Canada, and Britain 5. Afro-Caribbean philosophy 6. African philosophy Conclusion.
Reinterpreting the French Revolution: A Global-Historical Perspective

This book provides a synthesis of the most recent scholarly literature on the diplomatic, political, social, economic, and cultural history of eighteenth-century and revolutionary France. On the basis of that synthesis, and current theoretical writing on major modern revolutions, the book argues that the outbreak of the French Revolution, and the dramatic developments of the subsequent ten years, were attributable to the interacting pressures of international and domestic politics on those national leaders attempting to govern France and to modernize its institutions. The book furthermore contends that the Revolution of 1789–1799, reconceptualized in this fashion, needs to be placed in the larger contexts of 'early modern' and 'modern' French history and modern 'progressive' sociopolitical revolutions. In staking out these positions, the book offers a unique interpretation of the French Revolution, one that dissents from both the Marxian socioeconomic orthodoxy of earlier times and more recent 'political-cultural' analyses.
Mysticism Matters: Distinguishing between Intrinsic Religiosity, Extrinsic Religiosity, and Spirituality Using Higher-order Factors of Personality and Mysticism

The current study was designed to examine factors of personality and mystical experience that might predict the extent to which participants were intrinsically religious, extrinsically religious, and/or spiritual, while controlling for gender and race. Data from 777 introductory psychology students were used. Hypotheses were partially supported with three hierarchical multiple regression analyses. The personality factors traditionalism and transformation were found to be modest differentiating predictors of the three criterion variables. However, the three factors of mysticism, introvertive, extrovertive, and religious interpretation mysticism, were found to predict substantial differentiating variance between intrinsic religiosity and spirituality.
Isolation and purification of a granulosis virus from infected larvae of the Indian meal moth, Plodia interpunctella

A procedure was developed for purification of a granulosis virus inclusion body produced in vivo in the Indian meal moth, Plodia interpunctella (Hubner). Purification was accomplished by differential centrifugation, treatment with sodium deoxycholate, and velocity sedimentation in sucrose gradients. The adequacy of the procedure was confirmed by mixing experiments in which uninfected, radioactively labeled larvae were mixed with infected, unlabeled larvae. After purification, the virus was shown to be free of host tissue, to retain its physical integrity, and to be highly infectious per os. Preparations of purified virus consisted of homogeneous populations of intact inclusion bodies (210 by 380 nm) whose buoyant density was 1.271 g/cm3 when centrifuged to equilibrium in sucrose gradients. Electron microscopy of thin-sectioned virus or of virus sequentially disrupted on electron microscope grids demonstrated three components: protein matrix, envelope, and nucleocapsid.
Multiple elements in the c-fos protein-coding region facilitate mRNA deadenylation and decay by a mechanism coupled to translation.

Abstract The c-fos proto-oncogene transcript is one of the most labile mammalian mRNAs known. Rapid degradation of c-fos mRNA is mediated by both the c-fos protein-coding region and an AU-rich element in the 3'-untranslated region. Here we present evidence that the c-fos coding region contains multiple destabilizing elements that can function independently to facilitate both deadenylation and decay of mRNA. The ability of these coding region destabilizing elements to direct deadenylation and decay requires the assembly of ribosomes at the 5' end of this domain and, most likely, translation of the message.
Dynamic stiffness enhancement of direct linear motor feed drives for machining

Linear motion electric motors have shown promising potential for use as next generation machine tool feed drives since they can increase machining rates and improve servo accuracy by eliminating gear related mechanical problems. To combat chatter instability, large dynamic stiffness is desirable in the servo control loop. This paper investigates the use of optimal H/sub /spl infin// control to design for large stiffness. Position feedback alone is first considered, with cutting force feedback later added to augment closed loop stiffness. Optimal position feedback is experimentally seen to achieve up to a 46% stiffness improvement over that achievable with proportional derivative control. The addition of force feedback to the servo loop resulted in a further 70-100% stiffness improvement over the position feedback alone values.
Ocean bottom tiltmeter developed for submarine volcano monitoring

Most of the oceanic crust is formed by intrusive processes, yet these processes at mid-ocean ridges are poorly understood when compared to on-land volcanos that are well monitored with respect to their surface deformation and seismic activity. This limited knowledge of tectonic processes at mid-ocean ridges stems from an absence of direct observations and inhibits our understanding of their magmatic segmentation, and many first-order magmatic processes, including fractionation and mixing. As a means to improve this situation, we have installed tiltmeters in the Scripps Ocean Bottom Seismographs (OBS) and begun initial performance testing in sediment and hard rock environments. These tests indicate that the TILT-OBS is now ready for realistic, designated testing on submarine volcanos. Such tests may be in the form of a rapid response monitoring of recently discovered submarine volcanic activity, or as the first trial measurements of strain in more stable, mid-ocean ridge volcanos.
Failed Oort Clouds and Planetary Migration

Planet formation is accompanied by the formation of comet clouds. In systems where planets migrate on rapid timescales, the diffusive evolution of comet orbits may stall, resulting in a comet cloud intermediate between a flattened Kuiper Belt and a spherical Oort cloud. These `failed Oort clouds' may provide a `smoking gun', indicating that planetary migration has taken place. If some fraction of the scattered component consists of planetary embryos, it may be possible to observe transits of such bodies even when the planetary system is not edge-on to the line of sight.
Track Detection of Low Observable Targets Using a Motion Model

A method for detecting a low observable target track using an acceleration-based overall motion model is proposed. Unlike the existing track-before-detect methods that are based on sequential state updates, this method computes integrated echo energy for the entire hypothesized motion. The detection and the estimation of the track are made simultaneously using the batch processing approach. A comparison of track detection probability shows higher performance against low observable targets. Using a motion similarity metric and motion model homogeneity, a performance prediction model is derived and compared with the simulation results.
Transmedia as experimental ethnography: The Exit Zero Project, deindustrialization, and the politics of nostalgia

How might “transmedia” approaches—or working across media—fit into histories of textual and visual innovation within anthropology, and what might they contribute to the discipline in the current moment? I explore this question through the Exit Zero Project, which includes a book, documentary film, and planned interactive website that examine the impact of deindustrialization on Southeast Chicago and the relationship between industrial job loss and expanding class inequalities in the United States. While the book and film take an “autoethnographic” approach, the website is based on collaboration with a local museum. I argue that transmedia ethnography both provokes new research questions and supports a growing interest in public anthropology by offering diverse spaces for engagement with subjects and audiences.
A changing nutrient regime in the Gulf of Maine.

Abstract Recent oceanographic observations and a retrospective analysis of nutrients and hydrography over the past five decades have revealed that the principal source of nutrients to the Gulf of Maine, the deep, nutrient-rich continental slope waters that enter at depth through the Northeast Channel, may have become less important to the Gulf's nutrient load. Since the 1970s, the deeper waters in the interior Gulf of Maine (>100 m) have become fresher and cooler, with lower nitrate (NO 3 ) but higher silicate (Si(OH) 4 ) concentrations. Prior to this decade, nitrate concentrations in the Gulf normally exceeded silicate by 4–5 μM, but now silicate and nitrate are nearly equal. These changes only partially correspond with that expected from deep slope water fluxes correlated with the North Atlantic Oscillation, and are opposite to patterns in freshwater discharges from the major rivers in the region. We suggest that accelerated melting in the Arctic and concomitant freshening of the Labrador Sea in recent decades have likely increased the equatorward baroclinic transport of the inner limb of the Labrador Current that flows over the broad continental shelf from the Grand Banks of Newfoundland to the Gulf of Maine. That current system now brings a greater fraction of colder and fresher deep shelf waters into the Gulf than warmer and saltier offshore slope waters which were previously thought to dominate the flux of nutrients. Those deep shelf waters reflect nitrate losses from sediment denitrification and silicate accumulations from rivers and in situ regeneration, which together are altering the nutrient regime and potentially the structure of the planktonic ecosystem.
SU‐FF‐T‐136: Improved Dose Characteristics From Proton Arc Therapy

Purpose:IMRT is common for x‐ray treatment, but protontreatment is still only performed at a few angles. Expanding protonradiation therapy to many angles may reduce dose to surrounding tissue. Beam technologies are moving forward (e.g., dielectric wall accelerator) making this practicable. This study seeks to quantify the reduction in dose to surrounding healthy tissue using proton arc therapy. Materials and Methods:Monte Carlo simulations were performed using Geant4. Proton beams impinged on a 100mm radius cylindrical water phantom with a 10mm radius treatment region. Protons were delivered equally over all angles with − r initial direction, producing kernals of rings of dose for each of several energies. Results: Reduction in dose outside of the treatment region is dramatic for the high dose regions. Single beam therapy PDD is presented, the entrance dose is a large portion of the total dose, with a >50% of peak dose from 60mm from peak. The entrance dose may be spread through the typical clinical use of 2 or 3 angles, but this still leaves significant entrance dose. The lateral drop off can be sharp though. The PDD is presented for proton arc therapy. The difference from the large entrance dose is significant. The distance to 50% dose is similar to the lateral drop‐off with traditional beams, and drops to 10% within 25mm of peak, leading to a much lower average dose to irradiated tissue outside the prescription area. Proton arc therapy has the conformity of the lateral dose — without similar entrance dose — of traditional proton therapy. Calculations are ongoing for avoidance regions and comparison with few angle treatments.Conclusions:Proton arc therapy shows great potential for reduction of high dose to tissues outside the treatment region compared with traditional protontreatment.
Application of the PM6 method to modeling the solid state

The applicability of the recently developed PM6 method for modeling various properties of a wide range of organic and inorganic crystalline solids has been investigated. Although the geometries of most systems examined were reproduced with good accuracy, severe errors were found in the predicted structures of a small number of solids. The origin of these errors was investigated, and a strategy for improving the method proposed.
Reduced representation approach to protein tertiary structure prediction: statistical potential and simulated annealing

Abstract A reduced representation model has been developed and used to predict the folded structures of proteins from their primary sequences and random starting conformations. The molecular structure of each protein is reduced to its backbone atoms (with ideal fixed bond lengths and valence angles) and each side chain approximated by a single virtual united atom. The co-ordinate variables are the backbone dihedral angles φ and ψ. A statistical potential function, which includes local and non-local interactions and is computed from known X-ray elucidated protein structures, is used in the structure minimization. Simulated annealing method of energy minimization is employed to search for folded conformations. Simulations using the reduced representation model reproduce many structural features of the studied proteins.
Experimental Evidence for Magnetic Exchange in Di- and Trinuclear Uranium(IV) Ethynylbenzene Complexes

We report the preparation and magnetic property investigations of a structurally related family of mono-, di-, and trinuclear U(IV) aryl acetylide complexes. The reaction between [(NN′3)UCl] and lithiated aryl acetylides leads to the formation of the hexacoordinate complexes [(NN′3)U(CCPh)2(Li·THF)] (1) and [(NN′3)2U2(p-DEB)(THF)] (2) as red-brown and yellow-green crystalline solids, respectively. In contrast, combining the uranacycle [(bit-NN′3)U] (bit-NN′3 = [N(CH2CH2NSitBuMe2)2(CH2CH2SitBuMeCH2]) with stoichiometric amounts of mono-, bis-, and tris(ethynyl) benzenes affords the yellow-green pentacoordinate arylacetylide complexes [(NN′3)U(CCPh)] (3), [(NN′3)2U2(m-DEB)] (4), [(NN′3)2U2(p-DEB)] (5), and [(NN′3)3U3(TEB)] (6), where NN′3 = [N(CH2CH2NSitBuMe2)3]. The measured magnetic susceptibilities for 1−6 trend toward non-magnetic ground states at low temperatures. Nevertheless, the di- and trinuclear pentacoordinate compounds 4−6 appear to display weak magnetic communication between the uranium centers...
A Conceptual Framework for Understanding the Stigmatization of Children of Incarcerated Parents

Stigmatization is often listed as one of the adverse consequences of parental incarceration; yet, there is very little research on this phenomenon. We address this knowledge deficit by providing a conceptual model of stigmatization and describing how it may apply to children with parents in jail or prison. This model helps to explain why families conceal the fact that a child’s parent is incarcerated; the potentially protective function of social withdrawal; possible links between stigmatization and childhood emotional and behavioral problems; how fear of stigmatization may impede help seeking; and the possibility for research and advocacy to contribute to the stigmatization of children who experience parental incarceration. It also helps to define specific aspects of stigmatization requiring further study.
An open-source automated platform for three-dimensional visualization of subdural electrodes using CT-MRI coregistration.

Summary Objective Visualizing implanted subdural electrodes in three-dimensional (3D) space can greatly aid in planning, executing, and validating resection in epilepsy surgery. Coregistration software is available, but cost, complexity, insufficient accuracy, or validation limit adoption. We present a fully automated open-source application, based on a novel method using postimplant computerized tomography (CT) and postimplant magnetic resonance (MR) images, for accurately visualizing intracranial electrodes in 3D space. Methods CT-MR rigid brain coregistration, MR nonrigid registration, and prior-based segmentation were carried out on seven patients. Postimplant CT, postimplant MR, and an external labeled atlas were then aligned in the same space. The coregistration algorithm was validated by manually marking identical anatomic landmarks on the postimplant CT and postimplant MR images. Following coregistration, distances between the center of the landmark masks on the postimplant MR and the coregistered CT images were calculated for all subjects. Algorithms were implemented in open-source software and translated into a “drag and drop” desktop application for Apple Mac OS X. Results Despite postoperative brain deformation, the method was able to automatically align intrasubject multimodal images and segment cortical subregions, so that all electrodes could be visualized on the parcellated brain. Manual marking of anatomic landmarks validated the coregistration algorithm with a mean misalignment distance of 2.87 mm (standard deviation 0.58 mm)between the landmarks. Software was easily used by operators without prior image processing experience. Significance We demonstrate an easy to use, novel platform for accurately visualizing subdural electrodes in 3D space on a parcellated brain. We rigorously validated this method using quantitative measures. The method is unique because it involves no preprocessing, is fully automated, and freely available worldwide. A desktop application, as well as the source code, are both available for download on the International Epilepsy Electrophysiology Portal (https://www.ieeg.org) for use and interactive refinement.
The intermediate filament vimentin regulates chondrogenesis of adult human bone marrow-derived multipotent progenitor cells.

Cytoskeletal proteins play important regulatory roles in a variety of cellular processes, including proliferation, migration, and differentiation. However, whereas actin and tubulin have established roles regulating developmental chondrogenesis, there is no evidence supporting a function for the intermediate filament vimentin in embryonic cartilage formation. We hypothesized that vimentin may regulate the chondrogenic differentiation of adult multipotent progenitor cells (MPCs), such as those involved in cartilage formation during bone fracture repair. As our model of adult progenitor cell chondrogenesis, we employed high-density pellet cultures of human bone marrow-derived MPCs. siRNA-mediated knockdown of vimentin mRNA and protein triggered a reduction in the extent of MPC cartilage formation, as evidenced by depressed accumulation of mRNAs for the cartilage-specific marker genes aggrecan and collagen type II, as well as reduced levels of Alcian blue-stainable proteoglycan and collagen II protein in the extracellular matrix. Moreover, mRNA and protein levels for the chondro-regulatory transcription factors SOX5, SOX6, and SOX9 were diminished by vimentin knockdown. Depleted cellular vimentin also induced a drastic reduction in PKA phosphorylation levels but did not affect the phosphorylation of multiple other chondro-regulatory kinases and transcription factors, including ERK1/2, p38, Smad2, and Smad1/5/8. Importantly, siRNA-mediated knockdown of PKA C-α mRNA and protein mimicked the reduction in chondrogenesis caused by diminished cellular vimentin. Finally, overexpression of vimentin in MPCs significantly enhanced the activity of a transfected collagen II promoter-luciferase reporter gene. In conclusion, we describe a novel role for the intermediate filament vimentin as a positive regulator of adult human bone marrow-derived MPC chondrogenesis. J. Cell. Biochem. 109: 265–276, 2010. Published 2009 Wiley-Liss, Inc.
Neuronal localization of serotonin in the nematode Ascaris suum.

We have used immunocytochemical techniques to investigate the distribution of serotonin-like immunoreactivity in the nematode Ascaris suum. Antisera raised against serotonin (5-hydroxytryptamine, 5-HT) conjugated to bovine serum albumin (BSA) labelled a pair of neurons in the pharynx of both sexes and five cells in the ventral cord of the male tail. The labelling was blocked by 5-HT or by 5-HT conjugated to BSA. The 5-HT-immunoreactive cells in the pharynx resemble neurosecretory cells and are probably homologous to the neurosecretory motor neurons (NSM) in Caenorhabditis elegans; the cells in the male tail appear to be motor neurons that are homologous to CP neurons in C. elegans. Other cells that stain with 5-HT antisera have been observed in C. elegans but are not seen in Ascaris. © 1996 Wiley-Liss, Inc.
Trimetallic ReBiPt complexes containing spiro-bismuth ligands from the reaction of the bis(tri-t-butylphosphine)platinum with Re3(CO)12(μ-BiPh2)(μ-H)2

Abstract Pt(P-t-Bu 3 ) 2 reacts with the bismuthtrirhenium complex Re 3 (CO) 12 (μ-BiPh 2 )(μ-H) 2 , 1 at 68 °C to give eight complexes PtRe 2 (CO) 9 P( t -Bu 3 )(μ-H) 2 , 2 , PtRe 3 (CO) 12 P( t -Bu 3 )(μ-Ph)(μ-H)(μ 4 -Bi), 3 , PtRe 3 (CO) 13 P( t -Bu 3 )(μ 4 -Bi)(μ-H) 2 , 4 , PtRe 4 (CO) 16 P( t -Bu 3 )(μ-H) 2 (μ 4 -Bi)(μ 3 -Bi), 5 , Pt 2 Re 5 (CO) 21 [P( t -Bu) 3 ] 2 (μ-H) 3 (μ 4 -Bi) 2 , 6 , trans -Pt 2 Re 5 (CO) 22 [P( t -Bu) 3 ] 2 (μ-H) 3 (μ 4 -Bi) 2, trans -7 , cis -Pt 2 Re 5 (CO) 22 [P( t -Bu) 3 ] 2 (μ-H) 3 (μ 4 -Bi) 2 , cis -7 , (an isomer of trans-7 ) and Re 3 (CO) 13 [PtPBu t 3 ] 2 (μ-H) 2 (μ 4 -Bi), 8 , all in low yields. When 4 was treated with Pt(P-t-Bu 3 ) 2 at 68 °C, compounds 2 , trans -7 , cis -7 , and Pt 2 Re 4 (CO) 18 [P( t -Bu) 3 ] 2 (μ-H) 2 (μ 4 -Bi) 2 , 9 were formed. When 8 was treated with CO at 25 °C, compounds 2 , trans -7 , 9 , and PtRe 3 (CO) 9 P( t -Bu) 3 (μ 3 -Bi)(μ 4 -Bi 2 ), 10 were formed. In all of the products both of the phenyl rings from the bridging BiPh 2 ligand of 1 were cleaved from the bismuth atom. Only compound 3 contains a phenyl ligand and that ligand was a bridging ligand across the Pt–Re bond. All of the products, except 10 , and the known compound 2 , contain spiro, μ 4 -Bi ligands. The higher nuclearity complexes 5 , 6 , trans -7 , cis -7 , and 9 contain two bismuth ligands. Compound 10 contains three bismuth atoms. Two of the bismuth atoms in 10 are part of an octahedrally-shaped Re 3 PtBi 2 cluster. The third bismuth atom is a triply-bridging ligand on the triangular Re 3 face of the cluster. When a mixture of 4 and 8 was heated to 68 °C in the presence of CO, the new compound PtRe 4 (CO) 17 (P- t -Bu 3 )(μ-H) 2 (μ 4 -Bi), 11 was formed. The molecular structures of all of the new complexes were characterized by single-crystal X-ray diffraction analyses.
In-vivo imaging of stimulus-evoked intrinsic optical signals correlated with retinal activation in anesthetized frog

Intrinsic optical signal imaging (IOS) promises a noninvasive method for high resolution examination of retinal function. Using freshly isolated animal retinas, we have conducted a series of experiments to test fast IOSs which have time courses comparable to electrophysiological kinetics. In this article, we demonstrate the feasibility of in vivo imaging of fast IOSs correlated with retinal activation in anesthetized frog (Rana Pipiens). A rapid (68,000 lines/s) line-scan confocal ophthalmoscope was constructed to achieve high-speed (200 frames/s) near infared (NIR) recording of fast IOSs. By rejecting out-of-focus background light, the line-scan confocal imager provided enough resolution to differentiate individual photoreceptors in vivo. With visible light stimulation, NIR confocal images disclosed transient IOSs with time courses comparable to retinal ERG kinetics. High-resolution IOS images revealed both positive (increasing) and negative (decreasing) light responses, with sub-cellular complexity, in the activated retina.
QRS complex fragmentation and survival following left ventricular assist device implantation

Abstract Background In patients with heart disease, the presence of a fragmented QRS complex (fQRS) on the surface electrocardiogram (ECG) is associated with an increased risk of mortality. We sought to evaluate the prevalence and location of fQRS before and after left ventricular assist device (LVAD) implantation and any associated risk of mortality. Methods and results Twelve-lead surface ECGs before (pre-LVAD, n = 98) and after (early [ Conclusions The prevalence of fragmented QRS on 12-lead ECG increases significantly in the anterior territory following LVAD implantation and is associated with decreased survival.
Tumor predisposition in mice mutant for p63 and p73: Evidence for broader tumor suppressor functions for the p53 family

Summary p63 and p73 are functionally and structurally related to the tumor suppressor p53 . However, their own role in tumor suppression is unclear. Given the p53 -like properties of p63 and p73 , we tested whether they are involved in tumor suppression by aging mice heterozygous for mutations in all p53 family genes and scored for spontaneous tumors. We show here that p63 +/− ; p73 +/− mice develop spontaneous tumors. Loss of p63 and p73 can also cooperate with loss of p53 in tumor development. Mice heterozygous for mutations in both p53 and p63 or p53 and p73 displayed higher tumor burden and metastasis compared to p53 +/− mice. These findings provide evidence for a broader role for the p53 family than has been previously reported.
The role of memory and concepts in learning

The extent to which concepts, memory, and planning are necessary to the simulation of intelligent behavior is a fundamental philosophical issue in Artificial Intelligence. An active and productive segement of the AI community has taken the position that multiple low-level agents, properly organized, can account for high-level behavior. Empirical research on these questions with fully operational systems has been restricted to mobile robots that do simple tasks. This paper recounts experiments with Hoyle, a system in a cerebral, rather than a physical, domain. The program learns to perform well and quickly, often outpacing its human creators at two-person, perfect information board games. Hoyle demonstrates that a surprising amount of intelligent behavior can be treated as if it were situation-determined, that often planning is unnecessary, and that the memory required to support this learning is minimal. Concepts, however, are crucial to this reactive program's ability to learn and perform.
Analytical solution for the Fermi-sea energy of two-dimensional electrons in a magnetic field: Lattice path-integral approach and quantum interference

We derive an exact solution for the total kinetic energy of noninteracting spinless electrons at half-filling in two-dimensional bipartite lattices. We employ a conceptually different approach that maps this problem exactly into a Feynman-Vdovichenko lattice walker. The problem is then reduced to the analytic study of the sum of magnetic phase factors on closed paths. We compare our results with the ones obtained through numerical calculations.
1:1 Ordered Domain Growth in Pb(Mg1/3Ta2/3)O3‐La(Mg2/3Ta1/3)O3 Relaxor Ferroelectric Perovskites

Single-phase perovskite solid solutions are formed across the entire (1 - x)Pb(Mg1/3Ta2/3)O3-xLa(Mg2/3Ta1/3)O3 (PLMT) pseudobinary system. Although as-sintered (1300°C, 3 h) samples with x lessthan equal to 0.1 adopt a phase-separated, “PMN-type” microstructure comprising small (2-3 nm) ordered domains dispersed in a disordered matrix, extensive domain growth and complete order can be induced by extended thermal annealing (1300°C, 24 h). These observations, and the alterations in the thermal stability and domain size across the system, can be interpreted using a charge-balanced random site model for the cation order. No evidence is found to support the space-charge models currently used to describe the cation ordering and properties of the corresponding niobate systems.
Malaria infections do not compromise vaccine-induced immunity against tuberculosis in mice.

Background Given the considerable geographic overlap in the endemic regions for malaria and tuberculosis, it is probable that co-infections with Mycobacterium tuberculosis and Plasmodium species are prevalent. Thus, it is quite likely that both malaria and TB vaccines may be used in the same populations in endemic areas. While novel vaccines are currently being developed and tested individually against each of these pathogens, the efficacy of these vaccines has not been evaluated in co-infection models. To further assess the effectiveness of these new immunization strategies, we investigated whether co-infection with malaria would impact the anti-tuberculosis protection induced by four different types of TB vaccines in a mouse model of pulmonary tuberculosis.
Suppression of Cancer Cell Migration and Invasion by Protein Phosphatase 2A through Dephosphorylation of μ- and m-Calpains

The mu- and m-calpains are major members of the calpain family that play an essential role in regulating cell motility. We have recently discovered that nicotine-activated protein kinase C iota enhances calpain phosphorylation in association with enhanced calpain activity and accelerated migration and invasion of human lung cancer cells. Here we found that specific disruption of protein phosphatase 2A (PP2A) activity by expression of SV40 small tumor antigen up-regulates phosphorylation of mu- and m-calpains whereas C2-ceramide, a potent PP2A activator, reduces nicotine-induced calpain phosphorylation, suggesting that PP2A may function as a physiological calpain phosphatase. PP2A co-localizes and interacts with mu- and m-calpains. Purified, active PP2A directly dephosphorylates mu- and m-calpains in vitro. Overexpression of the PP2A catalytic subunit (PP2A/C) suppresses nicotine-stimulated phosphorylation of mu- and m-calpains, which is associated with inhibition of calpain activity, wound healing, cell migration, and invasion. By contrast, depletion of PP2A/C by RNA interference enhances calpain phosphorylation, calpain activity, cell migration, and invasion. Importantly, C2-ceramide-induced suppression of calpain phosphorylation results in decreased secretion of mu- and m-calpains from lung cancer cells into culture medium, which may have potential clinic relevance in controlling metastasis of lung cancer. These findings reveal a novel role for PP2A as a physiological calpain phosphatase that not only directly dephosphorylates but also inactivates mu- and m-calpains, leading to suppression of migration and invasion of human lung cancer cells.
Disk and shells revisited

(1991). Disks and Shells Revisited. The American Mathematical Monthly: Vol. 98, No. 2, pp. 154-156.
Performance evaluation of G-tree and its application in fuzzy databases

G-tree is a data structure designed to provide multidimensional access in databases. It has the self-balancing property of B+-tree. In this paper, performance evahtation of G-tree is provided for various data distributions. For point queries, the experiments show that its retrieval and update performance is similar to that of l?+-trees independently of the data distribution. For range queries, the performance varies significantly with the data distributions. While the performance is good for the 2-dimensional case, it deteriorates as the number of dimensions increases. This empirical evidence is confirmed by an analytical proof, which also yields a simple way of computing the expected number of data pages accessed. This analytical result which shows that the number of data pages accessed by a range query increases exponentially with the number of dimensions applies to many multi-dimensional schemes. We also apply the G-tree to fuzzy databases and show empirically that it has good performance for imprecise queries on relatively imprecise data. But it is less efficient for precise queries on relatively precise data.
Imaginary Placements: The Other Space of Cinema

This article explores the cultural and ideational imperatives that have shaped the architecture of the movie theater as an institution and a building type since inception. The focus of the article is on the early formative years of the movie theater design from the turn of the nineteenth century to the rise of movie palaces. The article outlines how the specifics of the design and the particular experience of the movie theater have, from the start, helped objectify and sustain our assumptions about the relationship between reality and representation. For example, one important element in my analysis will concern the movie theater’s facade, from its early days as vacant storefronts to the contemporary theater. It is the facade’s entryway, an architectural element that would become increasingly exotic, that would serve as the border between the real and the imaginary—the ticketed passageway from everyday life into the construed other world of the movies. This article, then, hopes to make a contribution toward understanding how architecture shapes our experience of the arts and of the world.
Effects of cuing in an “irrelevant” context

Normally, retention of an avoidance response by a rat is impaired when the test context is novel or does not correspond to the training context. Experiment 1 demonstrates that such an impairment of test performance can be alleviated if a rat receives a cuing treatment or reminder of training in the novel test context prior to testing. Experiment 2 indicates that when rats receive avoidance training in one context and then receive a reminder of training in a novel context, they perform more poorly when tested in the training context than do animals that receive no reminder. This finding is discussed in relation to current theories of contextual influence over retention performance.
Benzo[c]phenanthrene adducts and nogalamycin inhibit DNA transesterification by vaccinia topoisomerase.

Abstract Vaccinia DNA topoisomerase forms a covalent DNA-(3′-phosphotyrosyl)-enzyme intermediate at a specific target site 5′-C+5C+4C+3T+2T+1p↓N-1 in duplex DNA. Here we study the effects of position-specific DNA intercalators on the rate and extent of single-turnover DNA transesterification. Chiral C-1 R and S trans-opened 3,4-diol 1,2-epoxide adducts of benzo[c]phenanthrene (BcPh) were introduced at single N2-deoxyguanosine and N6-deoxyadenosine positions within the 3′-G+5G+4G+3A+2A+1T-1A-2 sequence of the nonscissile DNA strand. Transesterification was unaffected by BcPh intercalation between the +6 and +5 base pairs, slowed 4-fold by intercalation between the +5 and +4 base pairs, and virtually abolished by BcPh intercalation between the +4 and +3 base pairs and the +3 and +2 base pairs. Intercalation between the +2 and +1 base pairs by the +2R BcPh dA adduct abolished transesterification, whereas the overlapping +1S BcPh dA adduct slowed the rate of transesterification by a factor of 2700, with little effect upon the extent of the reaction. Intercalation at the scissile phosphodiester (between the +1 and -1 base pairs) slowed transesterification by a factor of 450. BcPh intercalation between the -1 and -2 base pairs slowed cleavage by two orders of magnitude, but intercalation between the -2 and -3 base pairs had little effect. The anthracycline drug nogalamycin, a non-covalent intercalator with preference for 5′-TG dinucleotides, inhibited the single-turnover DNA cleavage reaction of vaccinia topoisomerase with an IC50 of 0.7 μm. Nogalamycin was most effective when the drug was pre-incubated with DNA and when the cleavage target site was 5′-CCCTT↓G instead of 5′-CCCTT↓A. These findings demarcate upstream and downstream boundaries of the functional interface of vaccinia topoisomerase with its DNA target site.
Recent advances in heparin-induced thrombocytopenia.

Purpose of reviewHeparin-induced thrombocytopenia (HIT) is a prothrombotic complication of heparin therapy caused by antibodies against platelet factor 4/heparin complexes. Progress in our understanding of HIT has translated to improvements in treatment and patient outcomes. The objective of this re
Hemangiomas of the geniculate ganglion

Objective:To describe the presentation, evaluation, and management of patients with geniculate ganglion hemangioma.Study Design:Retrospective case review.Setting:Tertiary-care academic medical center.Patients:Six patients with hemangiomas of the geniculate ganglion, evaluated and managed at a single