cssi/SciSciGPT-SciSciNet huggingface dataset:
Mediation Modeling: Differing Perspectives on Time Alter Mediation Inferences

Time is unlike any other variable collected in the social, behavioral, and medical sciences. Research participants who are sampled, and variables that are measured, come in distinct, discrete units. Although time is often recorded in such discrete units (e.g., wave 1, grade 3, day 5), time is markedly different from either participants or variables. Sampling time points is unlike sampling people or variables, as there are an arbitrary number of additional samples that can be collected between any two occasions of measurement. These interstitial samples are ignored by many longitudinal modeling paradigms. These observations that occur between sampling occasions form the basis for the perspectives on mediation explored in this chapter. We focus on the difference in perspectives offered by discrete time approaches commonly utilized in mediation research versus models that conceptualize time as a continuous variable. The differences in how one conceptualizes time have the potential to alter such core mediation concepts as direct and indirect effect, complete and partial mediation, and even what constitutes a “mediation” model.
A phylogenetic analysis of conifer diterpenoids and their carbon isotopes for chemotaxonomic applications

Abstract Plant-derived diterpenoids are commonly used as conifer-specific biomarkers and for chemotaxonomic assignment or confirmation. Numerous studies have reported on the utility of diterpenoids as chemotaxonomic indicators, but few have quantitatively analyzed diterpenoid concentrations, especially with respect to conifer phylogeny. In addition, the carbon isotope values (δ13C) of diterpenoids provide a means to track conifer-specific δ13C values, which is useful for tracking water availability and the carbon cycle. To expand on previous work, we measured diterpenoid concentrations and carbon isotopes of 43 conifer species, and Ginkgo biloba, collected at the University of California Botanical Garden at Berkeley. In this collection, all extant conifer families and almost two-thirds of extant genera are present, including many subtropical and Southern Hemisphere groups that were once common and widespread components of fossil assemblages. Overall, we found diterpenoid concentrations were highly variable among species and families. Despite this variability, there is coarse family-level phylogenetic structuring with the lowest concentrations in Pinaceae. When diterpenoid concentrations are fitted to a model of trait evolution (Brownian motion), we however find that there is no phylogenetic signal. In contrast, when terpenoids are analyzed by the proportion of diterpenoid compound structure classes (abietanes, labdanes, pimaranes, tetracyclics, and totarols/sempervirol), there was significant phylogenic signal for the abietane and tetracyclic structures. Diterpenoid biosynthetic carbon isotope fractionation, as expressed between diterpenoids and leaf tissue (editerpenoid), also contained a phylogenetic signal, as well as the broad phylogenetic structuring observed in total diterpenoid concentrations. Overall, these results indicate that the Pinaceae is unique among conifer clades with respect to terpenoid structure classes, concentrations and editerpenoid. When diterpenoids are applied to taxonomic assignment of fossils, it would be useful to combine several traits (concentration, proportion, and editerpenoid). In this context, it should be possible to broadly distinguish three major conifer groups: Cupressaceae, Podocarpaceae and Pinaceae. However, based on these results, we recommend against assuming that closely related species have similar diterpenoid compositions.
New transcriptional circuit evolved by coding sequence changes in a master regulator followed by cis-regulatory changes in its target genes

Abstract While changes in both the coding-sequence of transcriptional regulators and in the cis-regulatory sequences recognized by them have been implicated in the evolution of transcriptional circuits, little is known of how they evolve in concert. We describe an evolutionary pathway in fungi where a new transcriptional circuit (a-specific gene repression by Matα2) evolved by coding changes in an ancient master regulator, followed millions of years later by cis-regulatory sequence changes in the genes of its future regulon. We discerned this order of events by analyzing a group of species in which the coding changes in the regulator are present, but the cis-regulatory changes in the target genes are not. In this group we show that the coding changes became necessary for the regulator’s deeply conserved function and were therefore preserved. We propose that the changes first arose without altering the overall function of the regulator (although changing the details of its mechanism) and were later co-opted to “jump start” the formation of the new circuit.
Specific Comment on the Paper Presented by Dr. H. N. Christensen

A further point should be emphasized about the scheme Dr. Christensen has described to explain the observed variations of the stoichiometric ratio of linked Na+ and amino acid fluxes. As pointed out previously, (Wheeler, K. P. and Christensen, H. N., J. Biol. Chem. 242, 3782 (1967)), the condition that the translocation step, whatever its molecular nature, is not rate-limiting enables us to explain all the experimental data in terms of the simplest ternary complex, NaES, without postulating the formation of complexes such as Na2ES, and so on. This condition not only removes the restriction that the stoichiometric ratio of the linked Na+ and amino acid fluxes must correspond with ratio present in the complex, but also can account for the various different kinetic curves that have been described. The nature of the curves formed by plotting the linked fluxes against the concentration of Na+ or the amino acid depends only on the relative values of the various rate constants for the individual reactions described in the scheme, not on the composition of the complex transported, and a variety of kinetic relationships, including hyperbolic and sigmoid curves, can be predicted from the scheme.
Misdiagnosis of Sepsis in Patients with Acutely Decompensated Heart Failure. Real World Outcomes

Introduction Acutely decompensated heart failure (ADHF) is a complex clinical syndrome that has a heterogeneous presentation often mimicked by multiple conditions, including sepsis. There is limited data on the prevalence and factors associated with sepsis misdiagnoses in patients experiencing ADHF. Methods This is a retrospective cohort study of patients admitted to tertiary cardiovascular center with a primary diagnosis of sepsis and heart failure (chronic or newly diagnosed) between January 2015 and December 2018. Primary outcomes include the prevalence of sepsis misdiagnosis in patients with ADHF. Secondary outcomes include analysis of factors associated with sepsis misdiagnoses in patients with ADHF. Results A total of 974 patients with a diagnosis of sepsis and a history of heart failure (HF) or newly diagnosed HF admitted to our institution between January 2015, and December 2018 were included in the study. Out of the 974 patients, 536 were male with a mean age of 75±14. Sepsis was misdiagnosed in 246/974 patients with ADHF. Current clinical and laboratory criteria used to diagnose sepsis and classify its severity (i.e., tachycardia, tachypnea, leukocytosis, organ dysfunction [i.e., elevated BUN, creatinine, lactic acidosis]) were significantly abnormal in both groups (Sepsis and no-sepsis [ADHF] patients. See table for baseline characteristics. All patients (974) received early sepsis-goal directed therapy including intravenous fluid administration. Conclusions This study suggests that standard clinical and laboratory criteria use to diagnose and classified sepsis are present in patients with ADHF. Sepsis can be misdiagnosed in up to 25% of the patients with ADHF, carrying a significant treatment consequence such as aggressive fluid administration. Further studies are recommended to test this hypothesis.
Antisense phosphorothioate oligonucleotides that downregulate the cellular expression of human ENT1 nucleoside transporter

5451 Nucleoside transporters are transmembrane proteins required for the cellular fluxes of physiological nucleosides important for salvage nucleotide biosynthesis and signal transduction. Nucleoside transporters have also been found to play a crucial role in nucleoside and to a less extend nucleobase chemotherapeutic drug uptake, thus affecting their efficacy. Nucleoside transporters also modulate the signal transduction actions of the physiological nucleoside adenosine in cardio- and neurovascular physiology. In these contexts, nucleoside transport inhibitors have demonstrated potential for clinical applications in cancer and anti-infective antimetabolite chemotherapy, as well as cardioprotection and neuroprotection in ischemic heart disease and stroke, respectively. In our program to develop inhibitors and probes for nucleoside transporters, we have designed and tested several antisense phosphorothioate oligonucleotides (ODNs) for their ability to downregulate the cellular expression of the human es (ENT1) nucleoside transporter. We will present results on a series of ODNs that were transfected into various human cell lines by liposomal delivery and their inhibitory effects on ENT1 transporter expression analyzed by flow cytometry and a new fluorescence microtitre plate assay. One of these ODNs, designated ES-1, significantly downregulated ENT1 transporter expression in human CEM and K562 leukemia cells, as well as human BeWo choriocarcinoma cells relative to nonspecific control ODN, and exhibited dose-dependency. Supported by NIH grant No. CA80730 from the National Cancer Institute.
Psychiatric Prescribing Patterns for Depression Treatment in an Outpatient Depression Clinic.

Objective To elucidate psychiatric prescribing patterns for depression treatment in patients being seen by an outpatient depression clinic as of 2018. Experimental Design Single-center, observational analysis. Principle Observation Selective serotonin receptor inhibitors are most commonly used by patients, and the majority of trials have adequate duration (2 months or longer). Conclusion Healthcare providers observed in this study follow depression treatment guidelines and ensure medications are given an adequate trial.
Sideband instability in a free electron laser

A two-dimensional, axisymmetric, time-dependent simulation code is used to examine the growth of sideband instabilities in a free electron laser amplifier. We examine the exponential growth and the nonlinear regimes. It is found that in a tapered wiggler, after an initial period of rapid increase in amplitude, the growth of sideband modes virtually ceases, saturating at a level substantially below that of the main signal.
Reinforcement Learning for Multi-Hop Scheduling and Routing of Real-Time Flows

We consider the problem of serving real-time flows over a multi-hop wireless network. Each flow is composed of packets that have strict deadlines, and the goal is to maximize the weighted timely throughput of the system. Consistent with recent developments using mm-wave communications, we assume that the links are directional, but are lossy, and have unknown probabilities of successful packet transmission. An average link utilization budget (similar to a power constraint) constrains the system. We pose the problem in the form of a Constrained Markov Decision Process (CMDP) with an unknown transition kernel. We use a duality approach to decompose the problem into an inner unconstrained MDP with link usage costs, and an outer link-cost update step. For the inner MDP, we develop model-based reinforcement learning algorithms that sample links by sending packets to learn the link statistics. While the first algorithm type samples links at will at the beginning and constructs the model, the second type is an online approach that can only use packets from flows to sample links that they traverse. The approach to the outer problem follows gradient descent. We characterize the sample complexity (number of packets transmitted) to obtain near-optimal policies, to show that a basic online approach has a poorer sample complexity bound, it can be modified to obtain an online algorithm that has excellent empirical performance.
Advanced eMAGE for highly efficient combinatorial editing of a stable genome

Abstract Eukaryotic multiplex genome engineering (eMAGE) offers a powerful tool to generate precise combinatorial genome modifications in Saccharomyces cerevisiae. We optimize the design of synthetic oligonucleotides and enrichment of edited populations to increase editing frequencies up to 90%, reduce workflow time by 40%, and engineer a tunable mismatch repair system to lower the rate of spontaneous mutations ∼17-fold. These advances transiently evade genome maintenance to introduce multiple edits at high efficiencies in a stable genetic background, expanding utility of eMAGE in eukaryotic cells.
Accurate and efficient structure-based computational mutagenesis for modeling fluorescence levels of Aequorea victoria green fluorescent protein mutants.

A computational mutagenesis technique was used to characterize the structural effects associated with over 46 000 single and multiple amino acid variants of Aequorea victoria green fluorescent protein (GFP), whose functional effects (fluorescence levels) were recently measured by experimental researchers. For each GFP mutant, the approach generated a single score reflecting the overall change in sequence-structure compatibility relative to native GFP, as well as a vector of environmental perturbation (EP) scores characterizing the impact at all GFP residue positions. A significant GFP structure-function relationship (P < 0.0001) was elucidated by comparing the sequence-structure compatibility scores with the functional data. Next, the computed vectors for GFP mutants were used to train predictive models of fluorescence by implementing random forest (RF) classification and tree regression machine learning algorithms. Classification performance reached 0.93 for sensitivity, 0.91 for precision and 0.90 for balanced accuracy, and regression models led to Pearson's correlation as high as r = 0.83 between experimental and predicted GFP mutant fluorescence. An RF model trained on a subset of over 1000 experimental single residue GFP mutants with measured fluorescence was used for predicting the 3300 remaining unstudied single residue mutants, with results complementing known GFP biochemical and biophysical properties. In addition, models trained on the subset of experimental GFP mutants harboring multiple residue replacements successfully predicted fluorescence of the single residue GFP mutants. The models developed for this study were accurate and efficient, and their predictions outperformed those of several related state-of-the-art methods.
Social Infrastructures and Building for Play

Architecture is a synthetic form of cultural production, one which weaves together social, aesthetic and functional agendas and has impacts at the scale of the individual and at the scale of the ci...
Generalized deformation of complex structures on nilmanifolds

Abstract On a 2-step nilmanifold with abelian complex structure, there exists an invariant ( 1 , 0 ) -form ρ such that dρ is type- ( 1 , 1 ) . It acts on the kernel of ρ by contraction. When this contraction map is non-degenerate, for any given infinitesimal generalized complex deformation Γ 1 we construct a solution ( Γ , ∂ → ) for the extended Maurer-Cartan equation. It amounts to identifying the obstruction ∂ → for Γ 1 to be integrable, and constructing the deformation Γ when the obstruction vanishes. As a consequence of our explicit solutions for ( Γ , ∂ → ) , we prove that on any real six-dimensional 2-step nilmanifold with abelian complex structure, when the contraction map is non-degenerate, every infinitesimal generalized complex deformation sufficiently close to zero is integrable. We also show that in all dimensions, if the contraction map is skew-Hermitian, then every infinitesimal generalized complex deformation sufficiently close to zero is integrable. Moreover the differential graded algebra controlling the generalized deformation of the underlying abelian complex structure is quasi-isomorphic to the one after deformation.
Are synthetic clinical notes useful for real natural language processing tasks: A case study on clinical entity recognition.

Objective : Developing clinical natural language processing systems often requires access to many clinical documents, which are not widely available to the public due to privacy and security concerns. To address this challenge, we propose to develop methods to generate synthetic clinical notes and evaluate their utility in real clinical natural language processing tasks. Materials and methods : We implemented 4 state-of-the-art text generation models, namely CharRNN, SegGAN, GPT-2, and CTRL, to generate clinical text for the History and Present Illness section. We then manually annotated clinical entities for randomly selected 500 History and Present Illness notes generated from the best-performing algorithm. To compare the utility of natural and synthetic corpora, we trained named entity recognition (NER) models from all 3 corpora and evaluated their performance on 2 independent natural corpora. Results : Our evaluation shows GPT-2 achieved the best BLEU (bilingual evaluation understudy) score (with a BLEU-2 of 0.92). NER models trained on synthetic corpus generated by GPT-2 showed slightly better performance on 2 independent corpora: strict F1 scores of 0.709 and 0.748, respectively, when compared with the NER models trained on natural corpus (F1 scores of 0.706 and 0.737, respectively), indicating the good utility of synthetic corpora in clinical NER model development. In addition, we also demonstrated that an augmented method that combines both natural and synthetic corpora achieved better performance than that uses the natural corpus only. Conclusions : Recent advances in text generation have made it possible to generate synthetic clinical notes that could be useful for training NER models for information extraction from natural clinical notes, thus lowering the privacy concern and increasing data availability. Further investigation is needed to apply this technology to practice.
Spectral efficient DWDM optical label switching technologies

We will demonstrate how to generate optical label and payload at high bit rates and realize label switching in a spectral efficient DWDM optical network by using optical carrier suppression and separation technique.
Imprisoning Rights: The Failure of Negotiated Governance in the Prison Inmate Grievance Process

Prisons are not meant to be particularly hospitable places; punishment as a goal of imprisonment implies a certain level of discomfort. Since the establishment of punishment by incarceration, prison conditions have had notably harsh effects upon the human body and mind.1 Although conditions have varied over time and between institutions, reformers have constantly 2 voiced concerns over the treatment of prisoners. Approximately four decades ago, federal courts began responding to complaints of inhumane treatment by applying the Constitutional Eighth Amendment prohibition against cruel and unusual punishment to demarcate a line between conditions of confinement that are uncomfortable and those that are unconstitutional.3 Along with the expansions of civil rights for inmates, courts mandated the costly reorganization of prisons. The prisons, once characterized by local autonomy and self-rule, were transformed into modern bureaucratic institutions designed
Oriented Hypergraphs: Introduction and Balance

An oriented hypergraph is an oriented incidence structure that extends the concept of a signed graph. We introduce hypergraphic structures and techniques central to the extension of the circuit classication of signed graphs to oriented hypergraphs. Oriented hypergraphs are further decomposed into three families — balanced, balanceable, and unbalanceable — and we obtain a complete classification of the balanced circuits of oriented hypergraphs.
An Application of Conventional Sovereign Debt Sustainability Analysis to the Current Debt Crises

The developing international debt crisis has unleashed unanticipated fears that governments in some advanced economies may default on their sovereign debt and trigger a global financial tsunami. This article provides a primer on sovereign debt sustainability and interprets the recent experience of advanced economies in the light of a uniform approach that allows an answer to this question: What are the main factors that contribute to make a country’s debt sustainable or unsustainable?
Instrumental Variables in Statistics and Econometrics

This article is reproduced from the previous edition, volume 11, pp. 7577–7582, © 2001, Elsevier Ltd.
Reactivation of motility of demembranated sea urchin sperm flagella.

Publisher Summary This chapter describes methods for spermatozoa from two sea urchin species that are readily available in the United States: Lytechinus pictus and Strongylocentrotus purpurutus. Both are cold water species, and the spermatozoa are damaged by high temperatures. Of the two species described here, L. pictus spermatozoa are less temperature sensitive and probably are not seriously damaged until the temperature exceeds 22°C. Iron contamination is a particularly serious problem with light sources that transmit significant power in the UV spectrum. The use of a UV filter is recommended. Solutions containing labile components should be made fresh for each day's work; the basic buffer solutions can safely be made up and refrigerated for use over 2 to 3 days. In the following recipes, Tris buffer refers either to trishydroxymethylaminomethane, in base form, with the solution pH lowered to 8.2 with acetic acid, or to an equimolar mixture of Tris base and Tris-HC1 that will give the desired pH with minimal adjustment. The procedures described here are designed to prepare “potentially symmetric” sperm flagella that generate reasonably symmetric bending waves at low free Ca2+ concentrations. The low-frequency reactivation solutions produce movements with frequencies of 1 to 2 cycles per second, and are particularly useful when observing with continuous illumination. The high-frequency reactivation solutions produce movement with frequencies of 30 to 40 cycles per second, comparable to the frequencies of live spermatozoa. When a drop of sperm suspension is placed on a microscope slide, the rapidly swimming spermatozoa quickly leave the interior of the drop and accumulate near surfaces, either sticking to the surface or swimming close to the surface with the plane of flagellar bending parallel to the surface. The chapter discusses the processes of reactivation of spermatozoa—Lytechinus pictus and strongylocentrotus purpuratus—, the required materials and detailed procedure.
Gastransport zwischen Lunge und Gewebe

Die Partialdruckgradienten fur O2 und CO2 (in Abb. 35–1 graphisch dargestellt), bilden den Schlussel zum Verstandnis der Gasbewegung; O2 „stromt“ aus der Luft durch die Alveolen und das Blut ins Gewebe „bergab “, wahrend sich CO2 dem Gefalle entsprechend vom Gewebe zu den Alveolen bewegt. Die vom und zum Gewebe transportierten Mengen beider Gase waren unzureichend, wurde nicht der im Blut geloste 02 an den O2-transportierenden Eiweiskorper Hamoglobin gebunden und das geloste CO2 durch eine Reihe reversibler chemischer Reaktionen in andere transportfahige Verbindungen ubergefuhrt werden.
Reforming power markets in developing countries : what have we learned?

This paper broadly follows the structure of the World Bank's Operational Guidance Note (OGN) for Public and Private Roles in the Supply of Electricity Services. Following the overview in chapter 1, the rest of chapter 2 sets out the techno-economic basis and the importance of political and institutional factors for reforming power markets in developing countries. Chapter 3 covers the current extent and outcomes of power market reform in developing countries. Chapter 4 covers enterprise restructuring and corporate governance, including the respective roles of state-owned enterprises and private enterprises in the provision of electricity services. Chapter 5 covers market structure, including restructuring power systems, the experience with independent power producers, and competition in the power market. Chapter 6 covers regulation of power markets. Chapter 7 covers ways that power market reform can support access and affordability to electricity services for the poor. The final chapter of the paper -- chapter 8 -- covers reform implementation, which complements the subjects covered by the OGN. The chapter covers three main aspects: (a) the challenges for implementing power market reform, including governments' roles and responsibilities in this endeavor; (b) the sequencing of power market reform; and (c) managing reform transition, especially the importance of starting conditions. The appendix to the paper examines the relevance of experience with power market reform in OECD countries for reform in developing countries.
The Space of Love and Garbage

This chapter borrows its name from Ivan Klima’s provocative novel Love and Garbage. I wish to excavate and explore some aspects of Klima’s thought, and will be guided in this somewhat controversial undertaking by reflections on the problematic, if not largely dismissed and abandoned notion of “the spiritual present.” That there is a spiritual framework constitutive of our (and any) historical period — one that is not simply a function of the disparate actions and beliefs of countless disconnected individuals — has been an unfashionable claim in the twentieth century.88 We have already taken stock of the more secular alternatives this century has offered in its place. For the thresholder, however, the claim of a spiritual framework not only makes sense but is altogether indispensable. It witnesses to a recurrent experience and brings that increasingly uncertain “no longer, but not yet” in which contemporary life is being led, more intensely into focus.
A Computer-Assisted Self-Interview (CASI) Assignment in the MSW Classroom

ABSTRACT This article reviews the research regarding computer-assisted self-interviews and describes a specific program, the Addiction Severity Index-Multimedia Version (ASI-MV), a self-administered audio assessment of substance use as well as concurrent psychosocial problems. This program was integrated into a graduate substance abuse course through a simulated exercise intended to introduce students to computer-based assessments. Students (N = 21) later evaluated the exercise and their reactions to computerized assessment at the end of the semester. Overall, students reported increased assessment skills, more comfort with the use of computers to assess clients, and willingness to incorporate computers into social work practice.
Data structures and load balancing for parallel adaptive hp finite-element methods☆

Abstract Adaptive hp finite-element methods (FEM), in which both grid size h and local polynomial order p are dynamically altered, are very effective discretization schemes for the numerical solution of a large class of partial differential equations. However, these schemes generate computations that require dynamic and irregular patterns of data storage, access, and computation, making their use on multiprocessor machines very difficult. We describe here the development of a suite of data structures and load balancing techniques that addresses these concerns. The central idea is the use of a spatially local ordering of all data and computation using a key generated from geometric data using a space filling curves-based ordering for data storage, distribution, and access. We also evaluate the suitability of tree and table type data structures for adaptive meshing. Example applications and performance data complete the presentation.
Autonomous expression of the nic1 acetylcholine receptor mutation in zebrafish muscle cells.

Abstract The nic1 b107 ( nic1 ) mutation blocks expression of both functional and clustered acetylcholine receptors (AChRs) in zebrafish muscle. Normally, signaling between motoneurons and muscles regulates AChR clustering. To learn if signaling is affected and to identify the primary cellular target of the nic1 mutation, we made mosaic embryos by transplanting motoneurons and muscle precursors from wild-type to mutant embryos. Genotypically mutant muscle cells fail to cluster AChRs even when contacted by wild-type moteneurons, whereas genotypically mutant motoneurons induce AChR clustering on wild-type muscle cells. Moreover, mutant muscle cells fail to cluster AChRs under culture conditions that induce AChR clustering on wild-type cells. We conclude that the nic1 mutation acts autonomously in muscle cells rather than by affecting signaling between motoneurons and muscle. The wild-type nic1 gene is necessary in muscle for expression and clustering of AChRs.
Effects of increasing acidity on aquatic protozoan communities.

Laboratory tests were conducted to evaluate the chronic effects of increased acidity on protozoan communities. Taxonomic richness of the protozoan component of these communities was severely affected at pH ≤ 5.33. Taxonomic composition was significantly affected at much higher pH. A permissible concentration was defined as the pH affecting no more than 20% of the species and estimated from concentration-response regression as 6.92 (5.92 to 8.04) pH units. A similar value estimated from more conventional chronic toxicity tests was 6.28 (6.16 to 6.45) pH units. Bacterial abundance decreased at pH levels ≤ 5.34 pH units. Other nontaxonomic responses (e.g., biomass, algal biomass, fungal biomass, net oxygen metabolism) were not sensitive to increases in acidity.
Loading effects on A0 Lamb-like waves in full and partially filled thin-walled tubes

Abstract We report the results of two experiments on water's loading effects on the lowest order flexural Lamb-like wave (A0 mode) in a stainless steel thin-walled cylinder and in an aluminum thin-walled cylinder. The experiments are interesting in that they analyze the case where the loading is on the internal wall of the cylinders only. The two cylinders provide a comparable reduction (21% and 25%) in the group velocity of the A0 wave. In addition, different effects are shown to occur in the two samples as a result of the difference in acoustic impedance match between the water and the stainless steel and aluminum shells. For the poor match of the stainless steel shell, the acoustic energy remains mostly in the tube wall, whereas in the case of the aluminum shell the match is relatively good, most of the acoustic energy is found to quickly leak into the water. The echoes received by pulse–echo technique demonstrate the difference in the path of an acoustic pulse in the two systems.
TU‐C‐BRB‐02: Identification of a Targeting Error in a Small Field Biological Irradiator Using 3D Dosimetry Techniques

Purpose: To characterize the targeting accuracy of a small animal irradiator, (XRad225Cx, Precision X‐Ray Inc.), producing 225kVp circular or square fields ranging from 1mm–40mm dimensions. Targeting accuracy is critical for accurate interpretation of pre‐clinical dose‐volume response, but is extremely challenging, due to the extremely small field sizes. Characterization was performed with a uniquely suited novel high‐resolution 3D dosimetry system. Methods: Targeting accuracy was evaluated on cylindrical 3D PRESAGE™dosimeters (5cm diameter, 7cm long) containing a range of physical targets. Each target corresponded to the tip‐point of a 1.3mm channel drilled into the dosimeter at various locations and depths. Conebeam‐CT image guided targeting was applied for treatment positioning, according to normal preclinical procedures. Each target was treated with 7 beam, varying angle, co‐planar plan using the 2.5mm circular cone, including a delivery to an undrilled position, for undisturbed optical‐CT data. Post‐treatment, the dosimeter was imaged with the Duke Midsized Optical‐CT Scanner (DMOS), producing 0.5mm isotropic 3D dose measurements. Targeting accuracy was evaluated by comparing the central position of the dose distribution to the targeted position (visible on optical‐CT). Results: High‐quality optical‐CT scans were obtained, revealing both the physical target and the delivered dose distribution. High‐resolution 3D analysis revealed a consistent targeting error of ∼1.5mm in all targets (along the long axis of the channel). The full‐width half maximum of the beam intersection region was 2.2mm. Intersection of the beam central axes showed an error of 1.1mm in the direction perpendicular to the long axis. Conclusions: The value of high‐resolution 3D dosimetry data was critical for this challenging problem of precisely evaluating the targeting accuracy of a very small field irradiator. The study enabled precise quantification of 3D targeting accuracy. The reason for the observed targeting errors is under investigation, and the accuracy of other cones will be explored. This work was supported by NIH R01CA100835, S103034539, NCI S10RR027610, NIAID K02AI093866 and NASA NSCOR NNX11AC60G. One potential conflict of interest is the dosimeter used in this work, PRESAGE™ is manufactured by Heuris Pharma, LLC, a company owned by John Adamovics.
Isolation of a candidate repressor/activator, NF-E1 (YY-1, delta), that binds to the immunoglobulin kappa 3' enhancer and the immunoglobulin heavy-chain mu E1 site.

Abstract We have determined that the developmental control of immunoglobulin kappa 3' enhancer (kappa E3') activity is the result of the combined influence of positive- and negative-acting elements. We show that a central core in the kappa E3' enhancer is active at the pre-B-cell stage but is repressed by flanking negative-acting elements. The negative-acting sequences repress enhancer activity in a position- and orientation-independent manner at the pre-B-cell stage. We have isolated a human cDNA clone encoding a zinc finger protein (NF-E1) that binds to the negative-acting segment of the kappa E3' enhancer. This protein also binds to the immunoglobulin heavy-chain enhancer mu E1 site. NF-E1 is encoded by the same gene as the YY-1 protein, which binds to the adeno-associated virus P5 promoter. NF-E1 is also the human homologue of the mouse delta protein, which binds to ribosomal protein gene promoters. The predicted amino acid sequence of this protein contains features characteristic of transcriptional activators as well as transcriptional repressors. Cotransfection studies with this cDNA indicate that it can repress basal promoter activity. The apparent dual function of this protein is discussed.
Modulation of Mitochondrial Function by Hydrogen Peroxide

During normal cellular metabolism, mitochondrial electron transport results in the formation of superoxide anion (O⨪2) and subsequently hydrogen peroxide (H2O2). Because H2O2 increases in concentration under certain physiologic and pathophysiologic conditions and can oxidatively modify cellular components, it is critical to understand the response of mitochondria to H2O2. In the present study, treatment of isolated rat heart mitochondria with H2O2 resulted in a decline and subsequent recovery of state 3 NADH-linked respiration. Alterations in NADH levels induced by H2O2 closely paralleled changes in the rate of state 3 respiration. Assessment of electron transport chain complexes and Krebs cycle enzymes revealed that α-ketoglutarate dehydrogenase (KGDH), succinate dehydrogenase (SDH), and aconitase were susceptible to H2O2 inactivation. Of particular importance, KGDH and SDH activity returned to control levels, concurrent with the recovery of state 3 respiration. Inactivation is not because of direct interaction of H2O2 with KGDH and SDH. In addition, removal of H2O2alone is not sufficient for reactivation. Enzyme activity does not recover unless mitochondria remain intact. The sensitivity of KGDH and SDH to H2O2-mediated inactivation and the reversible nature of inactivation suggest a potential role for H2O2 in the regulation of KGDH and SDH.
Investigating the procedural variables that determine whether rats will display negative anticipatory contrast or positive induction

Previous studies have demonstrated that consumption of a low-valued food substance may decrease if access to a high-valued substance will soon be available (negative anticipatory contrast). Research has also demonstrated that responding for a low-valued reinforcer may increase if responding for a high-valued reinforcer will soon be possible (positive induction). The present experiment employed rats to respond in a procedure similar to that typically used to produce negative anticipatory contrast. The goal was to determine what factors contribute to when a contrast or an induction effect will occur. Based on previous research, the influence of auditory cues, temporal delays, food deprivation, and location of substance delivery were investigated. Auditory cues and temporal delays did little to influence whether subjects increased or decreased their consumption of 1% sucrose when access to 32% sucrose was upcoming. The appearance of contrast or induction was related to level of deprivation, with deprivation promoting induction. Which effect occurred also depended on whether subjects consumed the two substances from one spout in one location (induction) or from two different spouts in two different locations (contrast). The present results help identify the procedural link(s) between these two effects. They also provide insight to why positive induction may occur (i.e., higher-order place conditioning).
MULTIVARIABLE HIGH-AUTHORITY CONTROL OF PLATE-LIKE ACTIVE STRUCTURES

A dynamic modeling capability for plate-like structures with integrated strain actuators is developed using the Rayleigh-Ritz assumed-mode method. The analytical model is utilized to design multi-input, multi-output (MIMO) controllers for active plate-like test articles. High control authority linear quadratic Gaussian (LQG) and optimal projection compensators are designed using a control-law development procedure that combines performance objectives, physical measurements, and LQG design variables in a consistent manner. The control laws are implemented using a real-time digital-control computer. In addition, a stability robustness guideline is developed to predict, a priori, the amount of control authority that can be applied to the test articles without destabilizing high-frequency modes. Closed-loop benchtop experiments are performed to verify the open-loop analytical model, the stability robustness predictions, and the control-law development procedure; the experiments demonstrate the ability of integrated strain actuators to effect high-authority MIMO control on flexible plate-like structures. The results show that considerable disturbance attenuation can be achieved both in the quasi-steady response and over large bandwidths spanning many flexible modes.
New insights regarding pharmacologic approaches for ovarian cancer prevention

The pathogenesis of epithelial ovarian cancer is not completely understood, but it commonly is believed that the process of recurrent ovulation (incessant ovulation) causes genetic damage in ovarian epithelial cells and that sufficient genetic damage can lead to ovarian cancer in susceptible individuals. Under this model, it has been suggested that reproductive and hormonal factors, such as pregnancy and oral contraceptive use, decrease ovarian cancer risk mainly via their inhibitory effects on ovulation. There is mounting evidence that the ovarian epithelium is a hormonally responsive target organ whose biology can be impacted strongly by the local hormonal environment. Progestin-mediated apoptotic effects may be a major mechanism underlying the ovarian cancer protective effects of pregnancy (a high progestin state) and oral contraceptive pill use. Similarly, retinoids, vitamin D, and non-steroidal anti-inflammatory drugs may have biologic effects on the ovarian epithelium that are cancer preventive, whereas androgens may have stimulatory effects on the ovarian epithelium, leading to an increased ovarian cancer risk.
Deforming nanocrystalline nickel at ultrahigh strain rates

The deformation mechanism of nanocrystalline Ni (with grain sizes in the range of 30–100 nm) at ultrahigh strain rates (>107s−1) was investigated. A laser-driven compression process was applied to achieve high pressures (20–70 GPa) on nanosecond timescales and thus induce high-strain-rate deformation in the nanocrystalline Ni. Postmortem transmission electron microscopy examinations revealed that the nanocrystalline structures survive the shock deformation, and that dislocation activity is a prevalent deformation mechanism for the grain sizes studied. No deformation twinning was observed even at stresses more than twice the threshold for twin formation in micron-sized polycrystals. These results agree qualitatively with molecular dynamics simulations and suggest that twinning is a difficult event in nanocrystalline Ni under shock-loading conditions.
The down regulation of neutrophil oxidative metabolism by S100A8 and S100A9: Implication of the protease-activated receptor-2

S100A8 and S100A9 regulate polymorphonuclear neutrophils (PMNs) recruitment and represent 40% of PMN cytosolic protein weight. We have shown that S100A8/S100A9 inhibit PMN oxidative metabolism. The present study was designed to elucidate the mechanisms of this anti-oxidative effect. We hypothesized that the protease activated receptor-2 (PAR-2) played a role in the down-regulation of PMN oxidative metabolism by S100A8/S100A9. Freshly isolated PMNs were tested for their ability to oxidize dichlorofluorescin-diacetate. Functional inhibition of PAR-2 with ENMD-1068, the pepducin P2pal-21 or an antibody directed at PAR-2 cleavage/activation site, resulted in a significant inhibition of S100A8 and S100A9 anti-oxidative effect. Conversely, the controlled activation of PAR-2 potentiated S100 anti-oxidative effect. Taken together, the data indicate that the anti-oxidative effect of S100A8/A9 is initiated by PAR-2 activation. S100A8/S100A9 may therefore dampen inflammation without interfering with its initial strength. This finding opens translational possibilities to limit deleterious PMN activation with a dual PAR-2/S100 strategy.
Phosphate release and force generation in cardiac myocytes investigated with caged phosphate and caged calcium

The phosphate (P(i)) dissociation step of the cross-bridge cycle was investigated in skinned rat ventricular myocytes to examine its role in force generation and Ca(2+) regulation in cardiac muscle. Pulse photolysis of caged P(i) (alpha-carboxyl-2-nitrobenzyl phosphate) produced up to 3 mM P(i) within the filament lattice, resulting in an approximately exponential decline in steady-state tension. The apparent rate constant, k (rho i), increased linearly with total P(i) concentration (initial plus photoreleased), giving an apparent second-order rate constant for P(i) binding of 3100 M(-1) s(-1), which is intermediate in value between fast and slow skeletal muscles. A decrease in the level of Ca(2+) activation to 20% of maximum tension reduced k (rho i) by twofold and increased the relative amplitude by threefold, consistent with modulation of P(i) release by Ca2+. A three-state model, with separate but coupled transitions for force generation and P(i) dissociation, and a Ca(2+)-sensitive forward rate constant for force generation, was compatible with the data. There was no evidence for a slow phase of tension decline observed previously in fast skeletal fibers at low Ca(2+), suggesting differences in cooperative mechanisms in cardiac and skeletal muscle. In separate experiments, tension development was initiated from a relaxed state by photolysis of caged Ca(2+). The apparent rate constant, k(Ca), was accelerated in the presence of high P(i) consistent with close coupling between force generation and P(i) dissociation, even when force development was initiated from a relaxed state. k(Ca) was also dependent on the level of Ca(2+) activation. However, significant quantitative differences between k (rho i) and k(Ca), including different sensitivities to Ca(2+) and P(i) indicate that caged Ca(2+) tension transients are influenced by additional Ca(2+)-dependent but P i-independent steps that occur before P(i) release. Data from both types of measurements suggest that kinetic transitions associated with P(i) dissociation are modulated by the Ca(2+) regulatory system and partially limit the physiological rate of tension development in cardiac muscle.
The genesis of neuronal diversity during development of cerebral cortex

Abstract The cerebral cortex is patterned into layers that contain neurons with characteristic morphologies, projection patterns and common cell ‘birthdays’. Transplantation studies of the developmental potential of cortical progenitor cells have revealed that these precursors are multipotent, heterochronic transplantation of cells taken early in the cell cycle yields postmitotic daughters that change their normal laminar fates. This result suggests that temporally regulated environmental cues influence the development of multipotent progenitors. Just before their final mitosis and well before initiating their migration into the cortex, young neurons make a commitment to the laminar identity typical of their birthday. Development involves a progressive series of decisions that restrict a cell's developmental potential; although the laminar identity of a neuron is specified at the time the cell is born, area-specific fates are malleable long afterwards.
On the Role of Congestion in Transportation Problems

In discussing the most efficient manner of distributing a product from several sources to numerous locations, Hitchcock [1] assumed that the specific transportation cost for a given shipping route was independent of the amount shipped over this route. In the present paper the problem is discussed under the assumption that the specific shipping cost for a route increases linearly with the amount shipped over this route. It is shown that the optimal shipping program then is unique and that it can be discussed either in terms of flows along the routes or in terms of accounting princes at the centers of production and consumption. A maximum principle is established for the accounting prices, which leads to a maximum characterization of the cost of the optimal program.
An examination of the relationship between the Economic Freedom Index value and the matching country specific exchange traded fund return

Purpose – The paper aims to determine if a country's Economic Freedom Index value has any relationship to the return of the related country specific exchange traded fund.Design/methodology/approach – A total of 36 country specific exchange traded funds were selected for use in this study. The historical returns for 2011, the three‐year period ending in 2011, and the five‐year period ending in 2011 were recorded if available for each exchange traded fund. Each exchange traded fund (ETF) was placed into one of four groups based upon its country's overall Economic Freedom Index value. The range of Economic Index values for each group was the same ones used by the publishers of the Economic Freedom Index. The mean ETF return and standard deviation for 2011, three‐year, and five‐year periods were calculated for each of the four groups. The mean/standard deviation of the Economic Freedom Index and each of its components for 2011, the mean of the three‐year period, and the mean of the five‐year period were calcu...