cssi/SciSciGPT-SciSciNet huggingface dataset:
Genetics and Genomics: Discovery, Validation, and Utility of Novel Tools for management of Prostate Cancer

Genomics is the science of how genes influence human health and disease states. It differs from traditional genetic screening in that the transcriptional activity (or other markers) in full panels of related genes are studied. Compared to simple genetic testing, assessment of expression levels in a panel of genes provides a more nuanced and holistic understanding of genetic modulation of human disease. Genomic testing may be used to great effect in resolving controversial questions on detection and treatment of prostate cancer. Genomic tests are currently in use for numerous facets of prostate cancer care, including screening, biopsy, and treatment planning. The clinical validity (predictive capacity) of these assays has been well established; studies on clinical utility (i.e. usefulness of these tests in guiding patient/provider decisions) have shown promising results. Men’s health specialists should be familiar with the role genomic testing will play in contemporary management of prostate cancer.
A ribonucleopeptide world at the origin of life

The structural flexibility of RNA and its ability to store genetic information has led scientists to postulate that RNA could be the key molecule for the development of life on Earth, further leading to formulate the RNA world hypothesis that received a lot of success and acceptance after the discoveries of the last thirty-five years. Despite its highly structural and functional significance, the difficulty in synthesizing the four nucleobases that form the RNA polymer from the same primordial soup, its low stability, and limited catalytic repertoire, make the RNA world hypothesis less convincing even though it remains the best explanation for the origin of life. An increasing number of scientists are becoming more supportive of a more realistic approach explaining the appearance of life. In this review, I propose an enhanced explanation for the appearance of life supported by recent discoveries and theories. Accordingly, amino acids and peptides associated with RNA (e.g., ribonucleopeptides) might have existed at the onset of RNA and might have played an important role in the continuous development of self-sustaining biological systems. Therefore, in this review, I cover the most recent and relevant scientific investigations that propose a better understanding of the ribonucleopeptide world hypothesis and the appearance of life. Finally, I propose two hypotheses for a primitive translation machinery (PTM) that might have been formed of either a T box ribozyme or a ribopolymerase.
Interpreting Aspect P

As discussed in Chapter 1, preposed temporal adverbials like the one in (1) have been argued to play a special role in the interpretation of tense and in the segmentation of discourse.
Characterization of the discriminative stimulus properties of the atypical antipsychotic amisulpride in C57BL/6 mice

CHARACTERIZATION OF THE DISCRIMINATIVE STIMULUS PROPERTIES OF THE ATYPICAL ANTIPSYCHOTIC AMISULPRIDE IN C57BL/6 MICE By Timothy John Donahue, MS, MA, M.Ed. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor Philosophy at Virginia Commonwealth University Virginia Commonwealth University, 2014 Major Director Joseph H. Porter, Ph.D. Professor, Department of Psychology Amisulpride, a benzamide derivative, is a second generation (atypical) antipsychotic drug used to treat both positive and negative symptoms of schizophrenia. Amisulpride is a relatively selective antagonist at dopamine D2 and D3 receptors and at serotonin 5-HT2B and 5-HT7 receptors. This is a unique binding profile as compared to both first generation (typical) and second generation antipsychotic drugs. It is approved in Europe and displays an atypical clinical profile with reduced extrapyramidal motor effects. The drug has a chiral center and is a mixture of two optical isomers: (S)-amisulpride and (R)-amisulpride. The therapeutic form of the drug is a mixture of these two enantiomers (rac-amisulpride). The present study used a two-lever drug discrimination assay to allow a direct comparison between amisulpride and its two isomers. Additionally, substitution testing was conducted with the typical antipsychotics haloperidol and chlorpromazine; the atypical antipsychotics olanzapine, clozapine, risperidone, quetiapine and aripiprazole; the antidepressants imipramine, fluoxetine, bupropion, mianserin; the anxiolytic
Molecular testing for indeterminate thyroid nodules: Performance of the Afirma gene expression classifier and ThyroSeq panel.

Background The ThyroSeq mutational panel and Afirma gene expression classifier (GEC) are used to risk stratify cytologically indeterminate thyroid nodules. In the current study, the authors evaluated the performance of these tests within the context of ultrasonographic features and with the incorporation of the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) nomenclature. Methods The authors reviewed nodules using ThyroSeq or Afirma GEC testing. For nodules that were surgically resected, both tests were studied within the context of ultrasound findings, comparing performance stratified by the 2015 American Thyroid Association guideline (ATA 2015) sonographic patterns and assessing the positive predictive value (PPV) of these tests both including and excluding NIFTP in the malignant category. Results A total of 304 cases were identified, 119 of which were resected. All cases that met the criteria for NIFTP on excision demonstrated either high-risk mutations on ThyroSeq or a "suspicious" result on Afirma GEC. When NIFTP cases were shifted from the malignant to nonmalignant category, the PPV of "positive" tests for both ThyroSeq and Afirma GEC decreased from 42.9% to 14.3% (an absolute decrease of 28.6%) and 30.1% to 25.3% (an absolute decrease of 4.8%), respectively. No cases of malignancy were found in the ATA 2015 "very low suspicion" group, even with a "suspicious" Afirma GEC result. Conclusions Both the ThyroSeq and Afirma GEC tests demonstrated decreases in the PPV when NIFTP was considered nonmalignant. In the era of NIFTP, a "positive" test result for either the Afirma GEC or ThyroSeq should be interpreted in light of clinical factors and should not exclude conservative (ie, lobectomy) surgical management. ATA 2015 "very low suspicion" nodules, even with "suspicious" Afirma GEC results, were not found to demonstrate malignancy in this series. Cancer Cytopathol 2018. © 2018 American Cancer Society.
Thermal Buckling of Symmetric Angle-ply Laminated Plates

An analysis of thermal buckling of symmetric angle-ply plates which are simply supported and subjected to a uniform temperature change is reported. The Rayleigh-Ritz technique is used to determine both the inplane stress resultants for the prebuckled state and the subsequent buckling behavior. Numerical results are presented for fiber-reinforced laminates, which show the effects of fiber orientation, number of layers, aspect ratio, and type of supports on the critical buckling temperature and the associated mode shape.
Modeling and on-line control of software and hardware systems

Statistics show that the cost of control software for computer-integrated manufacturing systems and other discrete-event systems is on the rise. Some of the important reasons behind these facts are: non-reusability and inflexibility. In prior work, we developed a methodology for designing control software that overcomes the above problems. It is based on assemblages of software/hardware components, formal models, and generic controllers. Rule-based models are used for specification purposes, and event-based models are used for control purposes. Generic controllers compute the control policy on-line, while allowing for changes in the models. This thesis expands the above concepts. First, a mechanism for "assembling" rule-based models is provided: Models of assembly components are given in terms of constituents' models, thus reducing the specification effort. Second, the supervisory control strategy of Ramadge and Wonham is adopted. Given an event-based model of the system, its behavior is restricted within a given specification under the presence of "uncontrollable" and "unobservable" events. We develop and formally study an on-line supervisory control scheme which avoids the pitfalls of off-line methods. This scheme involves three main algorithms. The first, VLP-S, assumes "total" behavior observation and efficiently generates the optimal behavior (the supremal controllable sublanguage of the specification). The second algorithm, VLP-PO, assumes only partial behavior observation. Under this condition, an optimal solution (a supremal) may not exist and off-line computations involve exponential complexities. Using a priority scheme, VLP-PO generates maximal observable and controllable sublanguages with a linear on-line computational effort. By varying the event priorities, different maximals and maximals containing the supremal controllable and normal sublanguage (a benchmark) can be generated. The third, DI-VLP-PO, a distributed version of VLP-PO, computes the control action on-line using several communicating agents. This reduces the computational effort by orders of magnitude, and with reasonable communication bounds. If the system has special structure, DI-VLP-PO recovers the policies of its sequential counterpart. Extensions of the algorithms to allow for "limited-lookahead", where only partial models are available, are provided (to handle infinite systems and time-constrained computation).
Beyond the genome: functional studies of phototrophic sulfur oxidation.

The increasing availability of complete genomic sequences for cultured phototrophic bacteria and assembled metagenomes from environments dominated by phototrophs has reinforced the need for a “post-genomic” analytical effort to test models of cellular structure and function proposed from genomic data. Comparative genomics has produced a testable model for pathways of sulfur compound oxidation in the phototrophic bacteria. In the case of sulfide, two enzymes are predicted to oxidize sulfide: sulfide:quinone oxidoreductase and flavocytochrome c sulfide dehydrogenase. However, these models do not predict which enzyme is important under what conditions. In Chlorobaculum tepidum, a model green sulfur bacterium, a combination of genetics and physiological analysis of mutant strains has led to the realization that this organism contains at least two active sulfide:quinone oxidoreductases and that there is significant interaction between sulfide oxidation and light harvesting. In the case of elemental sulfur, an organothiol intermediate of unknown structure has been proposed to activate elemental sulfur for transport into the cytoplasm where it can be oxidized or assimilated, and recent approaches using classical metabolite analysis have begun to shed light on this issue both in C. tepidum and the purple sulfur bacterium Allochromatium vinosum.
A new method for optimal step computation in gradient algorithms

In this paper a new method for the computation of the optimal step in gradient algorithms is presented. This method improves the convergence of the gradient algorithms and outperforms any other suboptimal scheme on linear problems while it does not require any additional storage.
Toward Zero Road Death Vision Assessment the Role Auto-Dependency, Public Health, and Active Transportation Modes: 2nd Highest Scoring Abstract: Early career/Post-doctoral

Background One of the most significant costs associated with automobile travel in the US is the number of road accidents and fatalities that this type of transportation incurs. To control these costs, in 2015, the USDOT announced that “zero road deaths” is the official policy of the US federal government transportation safety. This policy envisions zero deaths as the ultimate road safety goal. To achieve this ambition, we need a consistent understanding of all potential determinants of road safety in the national level. Accordingly, this research provides a framework to investigate the impact of a wide range of variables on traffic fatality rates (defined as deaths per 100,000 people). We particularly examine the effect of auto-dependency indicators, public health factors, and active transportation modes on the road safety outcomes. Methods For this purpose, a previously developed conceptual framework has been used which classified road safety contributing factors into seven separate sets: exposure, travel behavior, socio-economics, infrastructure and urban form, safety policies, and mitigating factors such as health care. This framework is tested using series of panel data models. These models investigate both spatial and temporal variations in safety patterns for the fifty states, along with DC, using annual data from 1997 to 2014. A complimentary analysis is conducted to assess the impact of factors which just available for few years of analysis like walking and biking variables. Results The results of our panel models illustrate that two variables Vehicle Miles Traveled and Vehicles per Capita , representing the level of auto-dependency, have the strongest impact on traffic fatalities. The elasticity analysis reveals that a 10% increase in VMT per vehicle is associated with 8.6% increase in road fatalities. Likewise, a 10% increase in vehicle ownership rate results in a 8.0% increase in road fatalities. This is closely followed by Infant Mortality Rates, the proxy that we used to represent the public health care. The results of complimentary analysis show that states with higher urban density, more walking, and more cycling are associated with lower traffic fatality rates. Conclusions Our findings suggest that if additional progress is to be made in reducing traffic fatalities, emphasis needs to move beyond simply focusing on policies such as seat belt laws. This research provides an order of factors influencing road fatalities, this order can help American policy makers to provide a more efficient road map for progress towards zero road death target.
Vaporization Detection Imaging: A Technique for Imaging Low-Boiling-Point Phase-Change Contrast Agents with a High Depth of Penetration and Contrast-to-Tissue Ratio

Phase-change contrast agents (PCCAs) possess advantages over microbubble contrast agents, such as the ability to extravasate and circulate longer in the vasculature that could enhance the diagnostic capabilities of contrast-enhanced ultrasound. PCCAs typically have a liquid perfluorocarbon (PFC) core that can be vaporized into echogenic microbubbles. Vaporization of submicron agents filled with liquid PFCs at body temperature usually requires therapeutic pressures higher than typically used for diagnostic imaging, but low-boiling-point PCCAs using decafluorobutane or octafluoropropane can be vaporized using pressures in the diagnostic imaging regime. Low-boiling-point PCCAs produce a unique acoustic signature that can be separated from tissue and bubble signals to make images with high contrast-to-tissue ratios. In this work, we explore the effect of pulse length and concentration on the vaporization signal of PCCAs and a new technique to capture and use the signals to make high contrast-to-tissue ratio images in vivo. The results indicate that using a short pulse may be ideal for imaging because it does not interact with created bubbles but still produces strong signals for making images. Furthermore, it was found that capturing PCCA vaporization signals produced higher contrast-to-tissue ratio values and better depth of penetration than imaging the bubbles generated by droplet activation using conventional contrast imaging techniques. The resolution of the vaporization signal images is poor because of the low frequency of the signals, but their high sensitivity may be used for applications such as molecular imaging, where the detection of small numbers of contrast agents is important.
Acute inhibition of protein deacetylases does not impact skeletal muscle insulin action.

Whether the histone deacetylase (HDAC) and sirtuin families of protein deacetylases regulate insulin-stimulated glucose uptake, independent of their transcriptional effects, has not been studied. O...
Improving the Quality of Care and Oxygen Utilization for Premature Infants

Purpose Chronic lung disease (CLD) is the most common morbidity affecting very low birth weight (VLBW) infants. Many of these infants are discharged home on oxygen, placing significant cost and emotional burdens on families and society. At our level III Intensive Care Nursery (ICN), despite previous improvement efforts, in 2014 34% of VLBW infants were discharged home with supplemental oxygen. This rate was an outlier compared to Vermont Oxford Network (VON) data. Our aim was to reduce the rate of VLBW infants discharged home from our ICN with oxygen by half within 1 year. Methods In …
A utility approach to individualized optimal dose selection using biomarkers.

In many settings, including oncology, increasing the dose of treatment results in both increased efficacy and toxicity. With the increasing availability of validated biomarkers and prediction models, there is the potential for individualized dosing based on patient specific factors. We consider the setting where there is an existing dataset of patients treated with heterogenous doses and including binary efficacy and toxicity outcomes and patient factors such as clinical features and biomarkers. The goal is to analyze the data to estimate an optimal dose for each (future) patient based on their clinical features and biomarkers. We propose an optimal individualized dose finding rule by maximizing utility functions for individual patients while limiting the rate of toxicity. The utility is defined as a weighted combination of efficacy and toxicity probabilities. This approach maximizes overall efficacy at a prespecified constraint on overall toxicity. We model the binary efficacy and toxicity outcomes using logistic regression with dose, biomarkers and dose-biomarker interactions. To incorporate the large number of potential parameters, we use the LASSO method. We additionally constrain the dose effect to be non-negative for both efficacy and toxicity for all patients. Simulation studies show that the utility approach combined with any of the modeling methods can improve efficacy without increasing toxicity relative to fixed dosing. The proposed methods are illustrated using a dataset of patients with lung cancer treated with radiation therapy.
The Missionary Nature of Tongues in the Book of Acts

This essay explores the way in which Luke presents tongues speech in Acts as the overcoming of crucial barriers to the forward movement of the Gospel in the Spirit’s power to the nations. In contrast to the fairly recent turn to holistic missions among many Pentecostal scholars, I argue that glossolalia represents strong support in Luke’s second volume for the narrow sense of missions that characterized the apostolic church and the beginnings of the modern Pentecostal movement. This perspective is argued for on the basis of the literary structure of Acts and various hindrances regarding the disciples movement to the nations.
Human mastadenovirus-B (HAdV-B)-specific E3-CR1β and E3-CR1γ glycoproteins interact with each other and localize at the plasma membrane of non-polarized airway epithelial cells.

Abstract The E3 region of all simian and human types classified within species Human mastadenovirus B (HAdV-B) encodes two unique highly conserved ORFs of unknown function designated E3-CR1β and E3-CR1γ. We generated a HAdV-3 mutant encoding small epitope tags at the N-termini of both E3-CR1β and E3-CR1γ (HAdV-3 N-tag wt) and a double knock out (HAdV-3 N-tag DKO) mutant virus that does not express either protein. Our studies show that HAdV-3 E3-CR1β and E3-CR1γ are type I transmembrane proteins that are produced predominantly at late times post infection, are glycosylated, co-localize at the plasma membrane of non-polarized epithelial cells, and interact with each other. At their extreme C-termini HAdV-B E3-CR1β and E3-CR1γ possess a conserved di-leucine motif followed by a class II PDZ domain binding motif (PBM). HAdV-3 E3-CR1β and E3-CR1γ are dispensable for virus growth, progeny release, spread, and plaque formation in A549 cells.
Health-related issues in youth with autism spectrum disorder

The purpose of this special issue is to bring attention to health-related issues in youth with autism spectrum disorder (ASD), with the intent to support pediatric medical and behavioral-health pro...
Adaptive Approach to Endovascular Management of Large Vessel Occlusion During the COVID-19 Pandemic.

Abstract Introduction The COVID-19 pandemic has resulted in unprecedented strain on the health care system. An adaptive strategy for the handling of thrombectomy for patients with large vessel occlusion has evolved at our center to optimize patient care while also minimizing risk of virus transmission. The purpose of this study was to evaluate the effects of the new thrombectomy protocol by comparing thrombectomy times and patient outcomes during the pandemic and pre pandemic period. Methods A retrospective cohort study was conducted on patients who underwent emergent thrombectomy from April 4th, 2020 to August 25th, 2020 (pandemic period) and between December 2nd, 2019 to April 3rd, 2020 (pre-pandemic period). The new protocol centered on a standardized approach to airway management in patients considered ‘high-risk’ for infection. An array of patient-specific factors and outcomes were compared between the two groups. Results A total of 126 patients were included in the study. There was no significant difference in door-to-recanalization or other time parameters between the two groups (138 minutes during the pandemic vs. 129 minutes pre-pandemic; p=0.37). However, outcomes measured as discharge modified Rankin Scale (mRS) were worse for patients during the pandemic (mRS ≤ 2, 10/58; 17.2% during pandemic vs. 24/68; 35.3% pre-pandemic, p = 0.02). No neurointerventional providers have been found to contract COVID-19. Conclusion Our approach to mechanical thrombectomy during the COVID-19 era was associated with similar recanalization rates but worse clinical outcomes compared to pre pandemic period. Further studies are necessary to identify factors contributing to worse outcomes during this ongoing pandemic.
Radical Interdependence: Buddhist Philosophical Foundations for Social Theory

This Chapter asserts that a Buddhist perspective provides a systematic and genuine alternative to Western models of IR not so much because it arose in Asia, but because it is founded on distinctive first-order philosophical principles or substructures that differ from those that dominate in the West. The chapter explains this fundamentally different worldview through the concept of “radical interdependence”—the basic Buddhist “truth” about the nature of our existence that departs from most Western understandings of reality and interdependence. Buddhism offers a different starting point for thinking about the world we live in, one it characterizes as deeply interdependent. Moreover, Buddhism maintains that the failure to appreciate the full extent of interdependence limits our human potential and is the ultimate source of all conflicts, up to and including interstate war, whereas an understanding the truth of radical interdependence is the key to imagining a different vision for politics and IR.
Dynamics of pollination and seed dispersal mutualisms at low density

Pollination and seed dispersal mutualisms are critical for biodiversity and ecosystem services yet face mounting threats from anthropogenic perturbations that cause their populations to decline. Characterizing the dynamics of these mutualisms when populations are at low density is important to anticipate consequences of these perturbations. We developed simple population dynamic models detailed enough to distinguish different mechanisms by which plant populations benefit from animal pollination or seed dispersal. We modeled benefits as functions of foraging rate by animals on plant rewards and specified whether they affected plant seed set, germination, or negative density dependence during recruitment. We found that pollination and seed dispersal mutualisms are stable at high density but exhibit different dynamics at low density, depending on plant carrying capacity, animal foraging efficiency, and whether populations are obligate upon their partners for persistence. Under certain conditions, all mutualisms experience destabilizing thresholds in which one population declines because its partner is too rare. Plants additionally experience Allee effects when obligate upon pollinators. Finally, both pollination and seed dispersal mutualisms that reduce mortality during recruitment can exhibit bistable coexistence at low or high density. Insights from our models can inform conservation efforts, as mutualist populations continue to decline globally.
The Numerical Unified Transform Method for the Nonlinear Schrödinger equation on the half-line.

We implement the Numerical Unified Transform Method to solve the Nonlinear Schrodinger equation on the half-line. For so-called linearizable boundary conditions, the method solves the half-line problems with comparable complexity as the Numerical Inverse Scattering Transform solves whole-line problems. In particular, the method computes the solution at any $x$ and $t$ without spatial discretization or time stepping. Contour deformations based on the method of nonlinear steepest descent are used so that the method's computational cost does not increase for large $x,t$ and the method is more accurate as $x,t$ increase. Our ideas also apply to some cases where the boundary conditions are not linearizable.
Catechol 2,3-dioxygenases functional in oxygen-limited (hypoxic) environments.

We studied the degradation of toluene for bacteria isolated from hypoxic (i.e., oxygen-limited) petroleum-contaminated aquifers and compared such strains with other toluene degraders. Three Pseudomonas isolates, P. pickettii PKO1, Pseudomonas sp. strain W31, and P. fluorescens CFS215, grew on toluene when nitrate was present as an alternate electron acceptor in hypoxic environments. We examined kinetic parameters (K(m) and Vmax) for catechol 2,3-dioxygenase (C230), a key shared enzyme of the toluene-degradative pathway for these strains, and compared these parameters with those for the analogous enzymes from archetypal toluene-degrading pseudomonads which did not show enhanced, nitrate-dependent toluene degradation. C230 purified from strains W31, PKO1, and CFS215 had a significantly greater affinity for oxygen as well as a significantly greater rate of substrate turnover than found for the analogous enzymes from the TOL plasmid (pWW0) of Pseudomonas putida PaW1, from Pseudomonas cepacia G4, or from P. putida F1. Analysis of the nucleotide and deduced amino acid sequences of C23O from strain PKO1 suggests that this extradiol dioxygenase belongs to a new cluster within the subfamily of C23Os that preferentially cleave monocyclic substrates. Moreover, deletion analysis of the nucleotide sequence upstream of the translational start of the meta-pathway operon that contains tbuE, the gene that encodes the C230 of strain PKO1, allowed identification of sequences critical for regulated expression of tbuE, including a sequence homologous to the ANR-binding site of Pseudomonas aeruginosa PAO. When present in cis, this site enhanced expression of tbuE under oxygen-limited conditions. Taken together, these results suggest the occurrence of a novel group of microorganisms capable of oxygen-requiring but nitrate-enhanced degradation of benzene, toluene, ethylbenzene, and xylenes in hypoxic environments. Strain PKO1, which exemplifies this novel group of microorganisms, compensates for a low-oxygen environment by the development of an oxygen-requiring enzyme with kinetic parameters favorable to function in hypoxic environments, as well as by elevating synthesis of such an enzyme in response to oxygen limitation.
An Incremental Approach to Scope-Bounded Checking Using a Lightweight Formal Method

We present a novel approach to optimize scope-bounded checking programs using a relational constraint solver. Given a program and its correctness specification, the traditional approach translates a bounded code segment of the entire program into a declarative formula and uses a constraint solver to search for any correctness violations. Scalability is a key issue with such approaches since for non-trivial programs the formulas are complex and represent a heavy workload that can choke the solvers. Our insight is that bounded code segments, which can be viewed as a set of (possible) execution paths, naturally lend to incremental checking through a partitioning of the set, where each partition represents a sub-set of paths. The partitions can be checked independently, and thus the problem of scope-bounded checking for the given program reduces to several sub-problems, where each sub-problem requires the constraint solver to check a less complex formula, thereby likely reducing the solver's overall workload. Experimental results show that our approach provides significant speed-ups over the traditional approach.
Superconductivity in a high magnetic field: Excitation spectrum and de Haas-van-Alphen oscillation

Abstract The excitation spectrum of a superconductor placed in the magnetic field high enough so that the inter-Landau level pairing can be ignored is shown to be gapless. The gap turns to zero at the set of points in the magnetic Brillouin zone which are in correspondence to the chosen vortex lattice in the real space. This leads to the algebraic temperature dependences of the thermodynamic potential, heat capacity and the amplitude of the dHvA oscillations at low temperatures.
Reply to: The Validity of the PET/α-[11C]Methy-L-Tryptophan Method for Measuring Rates of Serotonin Synthesis in Human Brain

Reply to: The Validity of the PET/α-[ 11 C]Methy- L -Tryptophan Method for Measuring Rates of Serotonin Synthesis in Human Brain
Numerical examples for the convergent robustness measures in nonlinear discrete-time systems

Certain aspects of constructing the largest class of asymptotically convergent (stable) systems which surrounds a convergent nonlinear system are presented. This study is also known as absolute stability or a sector problem. We present three numerical examples to show the applications of these results, namely, in: (i) linear systems with linear multiple parameter variations; (ii) nonlinear systems with linear multiple parameter variations and multiple nonlinearities; and (iii) linear systems with multiple nonlinear parameter variations. These building-blocks examples can be assembled to solve a complicated nonlinear system with multiple nonlinear parameter variations. >
Partial scan using multi-hop state reachability analysis

Sequential test generators fail to yield tests for some stuck-at-faults because they are unable to reach certain states necessary for exciting/propagating these target faults. Adding scan to the circuit increases reachability of these hard-to-reach and/or previously unreachable states. In this paper, we postulated that fewer scan flip-flops are needed to make these states reachable. The states necessary for detecting the hard-to-detect faults, when reached, will facilitate reaching other hard-to-reach states in one or more hops by the sequential test generator, resulting in significantly higher fault coverage. We collect information on the hard-to-reach, aborted, and easy states in our analysis. Results from our approach have indicated that higher fault coverage can be achieved with significantly fewer scan flip-flops for some circuits.
Early transonic ideas in the light of later developments

Abstract : A survey is given of early ideas about transonic flow and their current interpretation.
Oxygen chemisorption compressor study for cryogenic J-T refrigeration

Over twenty potentially reversible heat-powered oxide reactions have been studied and/or tested to determine their potential use as thermochemical oxygen compressors for cryogenic J-T LO2 refrigerators. One gas-solid compound family, Pr(1-n)Ce(n)O(x), proved to be completely reversible with fast kinetics for all pressure ranges tested below 650 C. With a heat-powered charcoal/methane physical adsorption upper stage and a Pr(1-n)Ce(n)O(x) chemisorption lower stage, temperatures should be attainable in the 55-80 K range for less power and over five times less weight than for charcoal/nitrogen sorption refrigeration systems. Total system power requirements with a hydride chemisorption lower stage (10 K to 7 K minimum) are about three times less than any mechanical refrigerator, and spacecraft refrigeration weights are about twenty times less. Due to the lack of wear-related moving parts in sorption refrigerators, life expectancy is at least ten years, and there essentially no vibration.
Teaching Social Studies Through the Performing Arts

Abstract This article focuses on a pilot project designed to prepare preservice social studies teachers on methods of teaching their content area using the performing arts. Participants’ reflections suggest that using the performing arts in social studies methods not only promotes student engagement and learning, but also gives voice to students who are rarely heard.
A Resource-Based Perspective On Corporate Environmental Performance And Profitability

Drawing on the resource-based view of the firm, we posited that environmental performance and economic performance are positively linked and that industry growth moderates the relationship, with the returns to environmental performance higher in high-growth industries. We tested these hypotheses with an analysis of 243 Finns over two years, using independently developed environmental ratings. Results indicate that “it pays to be green” and that this relationship strengthens with industry growth. We conclude by highlighting the study's academic and managerial implications, making special reference to the social issues in management literature.
Making Architecture Visible to Improve Flow Management in Lean Software Development

Lean practices use the principle of Little's law to improve the flow of value to the end user by eliminating sources of waste from a software development process. Little's law defines throughput as a ratio of work in process and cycle time. Increasing throughput (or productivity) requires continuously improving (that is, decreasing) cycle time while ensuring that the work-in-process limit doesn't exceed the capacity available to process the work. This article shares experiences regarding the role architecture plays in lean software management practices. Release plans that give as much emphasis to architecturally significant tasks as to feature-based high-priority functionality can achieve better outcomes by avoiding conditions that lead to wasted time and effort. The application of lean software development practices can improve with better practical guidance on how to manage architecture flow as well as feature flow.
Evolution by individuals, plant-herbivore interactions, and mosaics of genetic variability: The adaptive significance of somatic mutations in plants.

Differences in the pattern of organization of organisms may lead to different patterns of evolution, genetics and ecology, Plants and animals differ in their fundamental patterns of organization. Plants consist of a series of repeating units that compete with one another, while animals consist of mutually interdependent systems that cannot compete. As a result, plants may be able to take advantage of somatic mutations in ways that are not available to animals. Somatic mutations arising in plants can be inherited by naturally occurring mechanisms of sexual and asexual reproduction. Long life span, large clone size, and the complete regeneration of buds each year may permit an indivdual plant or clone to evolve. Plants may even develop as mosaics of genetic variation. Evolution by individual plants and/or development as mosaics of genetic variation may prevent herbivores from breaking the defenses of their host plants. This evolution may also result in greater “fine tuning” to local environments leading to ecotypic variation.
Dysregulation of CDK8 and Cyclin C in tumorigenesis

Appropriately controlled gene expression is fundamental for normal growth and survival of all living organisms. In eukaryotes, the transcription of protein-coding mRNAs is dependent on RNA polymerase II (Pol II). The multi-subunit transcription cofactor Mediator complex is proposed to regulate most, if not all, of the Pol II-dependent transcription. Here we focus our discussion on two subunits of the Mediator complex, cyclin-dependent kinase 8 (CDK8) and its regulatory partner Cyclin C (CycC), because they are either mutated or amplified in a variety of human cancers. CDK8 functions as an oncoprotein in melanoma and colorectal cancers, thus there are considerable interests in developing drugs specifically targeting the CDK8 kinase activity. However, to evaluate the feasibility of targeting CDK8 for cancer therapy and to understand how their dysregulation contributes to tumorigenesis, it is essential to elucidate the in vivo function and regulation of CDK8-CycC, which are still poorly understood in multi-cellular organisms. We summarize the evidence linking their dysregulation to various cancers and present our bioinformatics and computational analyses on the structure and evolution of CDK8. We also discuss the implications of these observations in tumorigenesis. Because most of the Mediator subunits, including CDK8 and CycC, are highly conserved during eukaryotic evolution, we expect that investigations using model organisms such as Drosophila will provide important insights into the function and regulation of CDK8 and CycC in different cellular and developmental contexts.
Topography and spatial population dualism in the People's Republic of China (1933-1990).

Looking at half a century of available data, a sharp spatial dualism is observed in the regional population distribution of the People's Republic of China. The vast share of the PRC's population is located in the Eastern and South-Eastem regions. Two topographical variables related to accessibility, distance from the eastern seaboard and elevation, seem to be at the core of this dualism. Their isolated and combined effects upon die spatial distribution of the PRC's population are examined for the period 1933–1990. It is documented that the population concentration in certain regions of the PRC is not so much because of their proximity to the seaboard, but because of their low elevation, especially in the eastern part of the nation. Also documented is a result indicating that in time the combined effects of these impedances on the regional population distribution in the PRC is linearly declining. Although policy issues are touched upon only slightly, the quantified linkages can be insightful to the PRC's efforts to more evenly distribute population over space (a demographic based policy), while still favoring the Eastern Seaboard (an economics based policy).
Production of l-Tryptophan by Mutants of Brevibacterium flavum Resistant to Both Tryptophan and Phenylalanine Analogues

5-Fluorotryptophan (5FT)-resistant mutants induced by one step mutation from a glutamate producing bacteria, Brevibacterium flavum No. 2247, accumulated only 0.4 g/liter of l-tryptophan at maximum. However, mutants resistant to higher concentrations of 5FT, which were further induced from the 5FT-resistant mutants, accumulated 1.4 to 2.4 g/liter of l-tryptophan. Their anthranilate synthetases of the tryptophan-specific pathway were less sensitive to the feedback inhibition by tryptophan than the parent enzymes and were not repressed by tryptophan. Moreover, the relationship between the l-tryptophan accumulation and the resistance of the enzymes to the feedback inhibition was parallel to a considerable extent. 3-Fluorophenylalanine (3FP)-resistant mutants induced from the 5FT-resistant mutants produced about twice as much l-tryptophan as the parental strains. Their l-tryptophan accumulation was not affected by the addition of excess l-phenylalanine and l-tyrosine, in contrast to that in the parents. Their ...
Epidermal growth factor and platelet-derived growth factor promote translocation of phospholipase C-γ from cytosol to membrane

Treatment of HER 14 cells with epidermal growth factor (EGF) or platelet-derived growth factor (PDGF) induced a translocation of phospholipase C-γ (PLC-γ) from cytosol to membrane. In such growth factor-treated cells, cytosolic PLC-γ was found to contain more phosphotyrosine than membrane-associated enzyme. Because these growth factors have been shown to promote both the physical association of PLC-γ with their receptors and the subsequent phosphorylation of the enzyme directly by the membrane-bound receptor tyrosine kinases, the membrane assocation of PLC-γ may simply be due to the formation of transient enzyme (receptor)-substrate (PLC-γ) complexes. If this is the case, membrane-associated PLC-γ would be expected to be released from membrane after undergoing tyrosine phosphorylation. However, tyrosine phosphorylation of membrane-associated PLC-γ by the EGF receptor in vitro did not result in the release of PLC-γ from membrane. Thus, the association of PLC-γ with membrane would appear to involve more than enzyme-substrate complex.
Phosphoramidate Derivatives Of Hydroxysteroids As Inhibitors Of Prostate-Specific Membrane Antigen

Prostate-specific membrane antigen (PSMA) is a membrane-bound cell surface peptidase which is over-expressed in prostate cancer cells. The enzymatic activities of PSMA are understood but the role of the enzyme in prostate cancer remains conjectural. We previously confirmed the existence of a hydrophobic binding site remote from the enzyme's catalytic center. To explore the specificity and accommodation of this binding site, we prepared a series of six glutamate-containing phosphoramidate derivatives of various hydroxysteroids (1a–1f). The inhibitory potencies of the individual compounds of the series were comparable to a simple phenylalkyl analog (8), and in all cases IC50 values were sub-micromolar. Molecular docking was used to develop a binding model for these inhibitors and to understand their relative inhibitory potencies against PSMA.
Control of the energy coupling modes in mitochondria by mercurials.

Mercurials and heavy metals induce the disappearance of one set of coupled functions including oxidative phosphorylation, and the appearance of another set including active transport of K/sup +/ and Mg/sup +2/. The minimal concentrations of fluorescein mercuric acetate required for disappearance and appearance respectively of these coupled functions are the same (in the range of 6-10 nmoles per mg protein). The inverse relation between the disappearance and the appearance of these two sets of coupling functions suggests that the energy transducing units in the mitochondria can exist in either of two coupling modes and that mercurials induce a transition from the oxidative phosphorylative mode to the K/sup +//Mg/sup +2/ transport mode. 2 figures, 1 table.
Winds from cataclysmic variables

Current understanding of the winds from Cataclysmic Variables is discussed, with particular emphasis on the understanding and modeling of the line profiles. Recent efforts at constructing such models are summarized, and a dynamical model is constructed which may serve to illustrate some of the physical principles acting in CV winds.
Neonate presenting with a midline supraumbilical raphe.

A newborn female (2.07 kg, 45.5 cm), who was born at 32 weeks gestation via an uncomplicated vaginal delivery, presented at birth with hypoglycemia and a midline sternal defect. Physical examination revealed an 8-cm supraumbilical linear defect (Fig. 1) with surrounding welldemarcated patchy areas of hypopigmentation on the central chest, chin, and lower lip and focal deeply erythematous macules on the nasal columella and left malar cheek. The neonate received phototherapy for hyperbilirubinemia and empiric antibiotics for presumed sepsis due to the exposed tissue from the sternal defect; however, her blood cultures remained negative. Thoracic ultrasonography showed no evidence of ectopia cordis. An echocardiogram revealed a patent foramen ovale with a small patent ductus arteriosus without other defects, and an EKG showed normal sinus rhythm. Over several days of life, she progressively developed prominent and widespread plaque-like facial hemangiomas along the jawline and bilateral malar cheeks, as well as on the left temporal scalp, periocular, and nasal regions (Figs. 2 and 3).
Gastroesophageal reflux, asthma, and mechanisms of interaction

Gastroesophageal reflux (GER) is a potential trigger of asthma. The esophagus and lung interact through a variety of mechanisms. Esophageal acid-induced bronchoconstriction can be provoked by a vagally mediated reflex, whereby acid in the distal esophagus produces airway responses; by neural enhancement of bronchial reactivity, whereby esophageal acid augments airway hyperresponsiveness; or by microaspiration, in which small amounts of esophageal acid in the upper airway cause significant airway responses. Interestingly, even in the microaspiration model, the vagus nerve plays a significant role. Neurogenic inflammation in the lung may occur with either vagally mediated mechanisms or with microaspiration. The prevalence of reflux symptoms, esophagitis, and abnormal esophageal acid contact time is higher in patients with asthma than in control populations. Potential mechanisms, whereby asthma may predispose to the development of GER, include autonomic dysregulation, an increased pressure gradient differential between the thorax and the abdomen, a high prevalence of hiatal hernia, alterations in crural diaphragm function, and bronchodilator medication use. Further research will help define how the esophagus and lung interact.
System-level parametric study of pulsed laser beam propagation

A numerical parametric investigation using a 2-level factorial design of experiments was performed to determine the effect of the f-number, sample position, sample thickness and the number of passes through the nonlinear optical sample on the beam transmittance through an optical system and on the threshold intensity. Calculated temperature profiles and excited state population dynamics are also reported. These results describe trends that are used in making decisions during the design process.
Dipeptidyl Peptidase I Controls Survival from Klebsiella pneumoniae Lung Infection by Processing Surfactant Protein D

Prior work established that a deficiency in the cysteine protease dipeptidyl peptidase I (DPPI) improves survival following polymicrobial septic peritonitis. To test whether DPPI regulates survival from severe lung infections, DPPI(-/-) mice were studied in a Klebsiella pneumoniae lung infection model, finding that survival in DPPI(-/-) mice is significantly better than in DPPI(+/+) mice 8d after infection. DPPI(-/-) mice have significantly fewer bacteria in the lung than infected DPPI(+/+) mice, but no difference in lung histopathology, lung injury, or cytokine levels. To explore mechanisms of enhanced bacterial clearance in DPPI(-/-) mice, we examined the status of pulmonary collectins, finding that levels of surfactant protein D, but not of surfactant protein A, are higher in DPPI(-/-) than in DPPI(+/+) BAL fluid, and that DPPI(-/-) BAL fluid aggregate bacteria more effectively than control BAL fluid. Sequencing of the amino terminus of surfactant protein D revealed two or eight additional amino acids in surfactant protein D isolated from DPPI(-/-) mice, suggesting processing by DPPI. These results establish that DPPI is a major determinant of survival following Klebsiella pneumoniae lung infection and suggest that the survival disadvantage in DPPI(+/+) mice is in part due to processing of surfactant protein D by DPPI.