cssi/SciSciGPT-SciSciNet huggingface dataset:
FEEDBACK DESIGN FOR UNSTABLE PLANTS WITH SATURATING NONLINEARITIES : SINGLE-INPUT, SINGLE-OUTPUT

Control systems are often required to operate in the presence of saturation nonlinearities, such as actuator displacement and rate limiting. Whereas the occurrence of saturation may possibly be minimized by the choice of closed-loop bandwidth, the nonlinearities themselves are essentially unavoidable, and system performance and even stability can be compromised when the nonlinearities are encountered. To address this problem, a design technique for improving the performance of single-input, single-output feedback systems operating in the presence of saturation nonlinearities is presented. The technique allows application to unstable plants and is an extension of that previously discussed in the literature for stable plants. A simple design example is provided that demonstrates the applicability of the methodology to a case of actuator rate limiting. Introduction and Background EEDBACK design techniques that explicitly consider the pos- sibility of control saturation are receiving increasing attention in the literature. Optimal control strategies for regulators employing inequality constraints on control and state variables are well known. * Techniques that attempt to minimize the adverse effects of saturation are also well established, e.g., antiwindup controllers.2 Feedback systems designed to avoid saturation have been discussed.3 Nonlin- ear feedback controllers designed with the goal of improved perfor- mance with state and control saturation have also been described.4 Finally, linear feedback schemes to improve the performance of systems with saturation nonlinearities have been formulated.5 The research to be described here falls into the last category. In particular, the treatment of actuator saturation as a nuisance nonlin- earity is pursued. This implies that the system in question experi- ences saturation relatively infrequently and that a nominal control system design was obtained ignoring any nonlinear actuation ef- fects. Such is the case for many aircraft flight control systems in which actuator saturation, either displacement or rate, is a relatively rare occurrence. The rarity of such occurrences is not accidental since the performance requirements of control surface actuators are typically an important part of flight control system specifications. Nonetheless, flight control actuator saturations do occur, typically, with high-performance aircraft.6"8 When conditionally stable sys- tems are involved (e.g., statically unstable aircraft), the results can be catastrophic.9-10 The design technique to be pursued is an extension of that devel- oped by Horowitz 5'11'12 and in Refs. 13 and 14 briefly outlined in the next section. Attention is focused on single-input, single-output (SISO) systems. The design equations are presented next, and the Horowitz technique is extended to unstable plants. The internal sta- bility and input-output stability of the resulting design approach are then discussed, and a simple example is presented which demon- strates the design approach.
A simple and efficient extension of a class of substructure based preconditioners to heterogeneous structural mechanics problems

Several domain decomposition methods with Lagrange multipliers have been recently designed for solving iteratively large-scale systems of finite element equations. While these methods differ typically by implementational details, they share in most cases the same substructure based preconditioners that were originally developed for the FETI method. The success of these preconditioners is due to the fact that, for homogeneous structural mechanics problems, they ensure a computational performance that scales with the problem size. In this paper, we address the suboptimal behaviour of these preconditioners in the presence of material and/or discretization heterogeneities. We propose a simple and virtually no-cost extension of these preconditioners that exhibits scalability even for highly heterogeneous systems of equations. We consider several intricate structural analysis problems, and demonstrate numerically the optimal performance delivered by the new preconditioners for problems with discontinuities. Copyright © 1999 John Wiley & Sons, Ltd.
Rational design of an enzyme mutant for anti-cocaine therapeutics

(−)-Cocaine is a widely abused drug and there is no available anti-cocaine therapeutic. The disastrous medical and social consequences of cocaine addiction have made the development of an effective pharmacological treatment a high priority. An ideal anti-cocaine medication would be to accelerate (−)-cocaine metabolism producing biologically inactive metabolites. The main metabolic pathway of cocaine in body is the hydrolysis at its benzoyl ester group. Reviewed in this article is the state-of-the-art computational design of high-activity mutants of human butyrylcholinesterase (BChE) against (−)-cocaine. The computational design of BChE mutants have been based on not only the structure of the enzyme, but also the detailed catalytic mechanisms for BChE-catalyzed hydrolysis of (−)-cocaine and (+)-cocaine. Computational studies of the detailed catalytic mechanisms and the structure-and-mechanism-based computational design have been carried out through the combined use of a variety of state-of-the-art techniques of molecular modeling. By using the computational insights into the catalytic mechanisms, a recently developed unique computational design strategy based on the simulation of the rate-determining transition state has been employed to design high-activity mutants of human BChE for hydrolysis of (−)-cocaine, leading to the exciting discovery of BChE mutants with a considerably improved catalytic efficiency against (−)-cocaine. One of the discovered BChE mutants (i.e., A199S/S287G/A328W/Y332G) has a ∼456-fold improved catalytic efficiency against (−)-cocaine. The encouraging outcome of the computational design and discovery effort demonstrates that the unique computational design approach based on the transition-state simulation is promising for rational enzyme redesign and drug discovery.
Modification of a high-performance liquid chromatographic—gas chromatographic procedure for separation of the 22 tetrachlorodibenzo-p-dioxin isomers

Abstract A published method for separation of the 22 tetrachlorodibenzo- p -dioxin (TCDD) isomers by high-performance liquid chromatography (HPLC)—gas chromatography (GC) was modified to improve the recovery and chromatographic resolution of individual isomers. For the first step, reversed-phase HPLC, minor changes were made in column temperature (50 to 40°C, to prolong column life) and in injection solvent (chloroform to benzene, to avoid photodecomposition). For the second step, normal-phase HPLC, the silica gel columns were used in a less active state, and 0.4% toluene was added to the hexane eluent as a polar orgnaic modifier. Resolution of the 22 isomers was significantly improved by this change of solvent system, and recovery of subnanogram quantities of TCDDs from the silica gel columns was increased from 20 to 80%. For the final step a capillary GC column (OV-275) was used in place of a packed column.
Increasing support for contraception as HIV prevention: stakeholder mapping to identify influential individuals and their perceptions.

Background Voluntary contraceptive use by HIV-positive women currently prevents more HIV-positive births, at a lower cost, than anti-retroviral drug (ARV) regimens. Despite this evidence, most prevention of mother-to-child transmission (PMTCT) programs focus solely on providing ARV prophylaxis to pregnant women and rarely include the prevention of unintended pregnancies among HIV-positive women. Methodology/Principal Findings To strengthen support for family planning as HIV prevention, we systematically identified key individuals in the field of international HIV/AIDS—those who could potentially influence the issue—and sought to determine their perceptions of barriers to and facilitators for implementing this PMTCT strategy. We used a criteria-based approach to determine which HIV/AIDS stakeholders have the most significant impact on HIV/AIDS research, programs, funding and policy and stratified purposive sampling to conduct interviews with a subset of these individuals. The interview findings pointed to obstacles to strengthening linkages between family planning and HIV/AIDS, including the need for: resources to integrate family planning and HIV services, infrastructure or capacity to provide integrated services at the facility level, national leadership and coordination, and targeted advocacy to key decision-makers. Conclusions/Significance The individuals we identified as having regional or international influence in the field of HIV/AIDS have the ability to leverage an increasingly conducive funding environment and a growing evidence base to address the policy, programmatic and operational challenges to integrating family planning with HIV/AIDS. Fostering greater support for implementing contraception for HIV prevention will require the dedication, collaboration and coordination of many such actors. Our findings can inform a targeted advocacy campaign.
Superpositioning of 3-dimensional neuroanatomic data sets.

Abstract Superpositioning of multiple 3-dimensional digital volumes is essential to extending neuroimaging capabilities from single-subject analysis to group evaluation. In this study, 6 rat heads were cryoplaned and digital images of the specimen blockface were organized into data volumes. The midline plane of each brain guided coronal and horizontal rotations and medial-lateral positioning. Four different methods of determining sagittal rotation, dorsoventral position, and anteroposterior position were tested. The first technique uses lambda and bregma as fiducial points; the second method employs bony sutures in the base of the skull; and the third strategy fits both sets of alignments points. The fourth method differs from the previous landmark-based, approaches by employing cross-correlation of image densities. A composite of midsagittal cutplanes through the volumes aligned by the first method revealed significant misalignment. Use of ventral fiducials resulted in improved correlation statistics for orthogonal cutplanes through the volumes and significantly reduced positional variability of anteroposterior landmarks. Combining dorsal and ventral fiducials produced a slight improvement in midsagittal image correlation but had mixed effects on landmark variability. Following the fourth method of registration, correlation statistics and the alignment of reference points were similar to those obtained with the 4-point approach.
Elemental Analysis of Aerosols Using Proton Scattering

Elemental analysis for all of the light elements up through chlorine by elastic scattering of 16 MeV protons has been shown to be feasible. Basic problems associated with such measurements are discussed including kinematics, angular distribution, and sample backings. Spectra are presented for air particulate matter for both a total filter (Nuclepore) and a size fractionated air impactor (polystyrene backed) sample. The method is absolute, non destructive and can be used in conjunction with proton induced x-ray fluorescence to quantitatively analyze all elements in the same sample in minutes of time.
Detection and quantitation of curcumin in mouse lung cell cultures by matrix-assisted laser desorption ionization time of flight mass spectrometry.

Abstract A method to detect and quantify curcumin and two curcuminoid metabolites in biological matrices, including mouse serum and mouse lung cell cultures, was developed. Standard curves between 0.04 and 10.00 nmol curcumin were prepared in serum, giving correlation coefficients of 0.94–0.99. Alcoholic extraction, concentration, and addition of dilute hydrochloric acid to stabilize the curcumin were essential to the reproducibility of the protocol. Untreated and curcumin-treated mouse lung fibrotic and nonfibrotic cell cultures were analyzed by matrix-assisted laser desorption ionization time of flight mass spectrometry utilizing this method. Curcumin uptake was calculated to be 7.0–11.6% for the saline-treated cells and 7.4–11.9% for the bleomycin-treated cultures. Curcumin was not detected in untreated cells. Two additional peaks ( m / z = 399 and 429) were observed in the curcumin-treated cells. These may be curcumin-derived products resulting from HCl treatment of the tissue samples.
The effect of graphene nanosheets on the mechanical properties of polyvinylchloride

In this work, excellent improvement in mechanical properties was observed by incorporating graphene nanofillers in polyvinyl chloride via solution blending. About 63% increase in modulus and 19% increase in ultimate tensile strength were measured at 1.5 wt% nanofiller content while almost no drop in elongation at break was observed. POLYM. COMPOS., 2014. © 2014 Society of Plastics Engineers
New materials design for laser hardening applications (Abstract Only)

New materials with fast non-linear optical (NLO) response over broad spectral bandwidths, macromolecular structures for optical switching and advanced absorbing dyes, which are critical for laser eye and sensor protection, are explored. The design of such novel materials requires that material properties are carefully optimized, for example, to achieve large NLO coefficients, high conjugation, appropriate ground and excited state absorption, as well as exhibit defined structural motifs, folding patterns and properties, especially when derivatized with NLO chromophores. A comparative study of porphyrins with meso-acetylene substituents carried out with the local density functional approximation, the gradient-corrected DFT, and HF calculations, is discussed in detail. The calculated electronic structures clearly show that the acetylene group contributes to the it-electron conjugation along the porphyrin ring, being consistent with experimental results. Recent calculations on variety of porphyrins are also reported. For reliable properties predictions, a fundamental understanding of solvent effects is important, and large molecules have to be modeled from first principles. We report calculations of interactions with the effective-fragment potential (EFP) method, where solvent molecules are placed around a solute to generate correctly the first solvation cell within an ab initio framework, using the parallelized GAMESS code, providing insight and good agreement with experiment. For example, we correctly predict the change in the most stable isomer for glutamic acid from the neutral form (gas-phase) to the zwitterionic form (in solution), by using the EFP method with a larger number of solvent fragments. A recent implementation of simulated annealing within EFP to optimize the positions of the fragment molecular systems is discussed. The development of global optimization techniques for determining energy minima of complex macromolecules is described. In addition, simulations to evaluate the properties of a polymer dispersed liquid crystal system of interest are discussed. The utilization of this approach to the study of liquid crystalline materials is described. These challenge applications in computational chemistry and materials science enable us to derive crucial structure-to-property relationships for candidate materials and enhance the capability for 'real materials' design and atomic-scale control, all of which utilize extensively scalable high-performance computing.
Information Machines and the Brave New World

Abstract This is an appraisal of the impact that the mechanization of knowledge has had upon modern society, and a search for the driving force behind this mechanization. The investigation starts by examining the multimodal structure of social systems, giving special consideration to the discrete modal orders that are found in a civilized and humane society. It proposes a multimodal definition of information that determines the information requirements of such a society. A distinction is then suggested between information systems and information machines, followed by an inquiry into the historical roots that have urged society to rely increasingly upon information machines for knowledge while dismissing information systems. The discussion concludes with some social illustrations that show the effect of mechanistic information upon modern lives.
The Effects of Temperature, Stress and Salinity on the Creep of Frozen Saline Soil

Gravel of the Prudhoe Bay area of Alaska used in the construction of artificial islands has been examined in constant load creep experiments to determine the effects of temperature, stress, and salinity on its creep behavior in unconfined compression. Over the range of conditions studied, it is found that the creep behavior is strongly dependent on each of these variables. In addition, the ice content of the specimen, itself a strong function of temperature and salinity, is found to be an important strength-determining parameter.
Audio cloud: creation and rendering

Word clouds are extensively used to present a summary of the prominent words in a document on the World Wide Web. Such clouds give the user an idea about the content of the document. In this paper we present a mechanism to create and render an audio cloud for audio content. Such audio clouds are expected to provide a similar summary of the audio documents. They have wide applicability in various domains, especially for low-literate users who currently do not use the Internet but interact with audio-based systems.Detecting words from an audio content is challenging, especially if the audio is in languages for which a speech recognition system does not exist. We present a language-independent mechanism to detect frequently occurring words within an audio document. We then present four ways to render these words that form an audio cloud. The four prototypes for rendering the audio cloud are based on varying the amplitude, the voice quality, echo and the repetition of audio words. An evaluation study conducted across 32 users suggests that literate and low-literate users easily understand the concept of audio cloud.
Perceived Racial Discrimination and Negative-Mood–Related Drinking Among African American College Students

Objective:Research consistently shows a positive association between racial discrimination and problematic alcohol use among African Americans, but little is known about the micro-processes linking this pernicious form of stress to drinking. One possibility is that the cumulative effects of discrimination increase individuals’ likelihood of negative-mood–related drinking. In the current study, we examined whether individual differences in lifetime perceived racial discrimination among African American college students moderate relations between daily negative moods and evening alcohol consumption in both social and nonsocial contexts.Method:Data came from an online daily diary study of 441 African Americans (58% female) enrolled at a historically black college/university. Lifetime discrimination was measured at baseline. For 30 days, students reported the number of drinks they consumed the night before both socially and nonsocially, as well as their daytime level of negative mood.Results:In support of the...
High and Mighty: Implicit Associations between Space and Social Status

Figurative language, the built environment, and our perceptuo-motor experiences frequently associate social status with physical space. Linguistic references such as high status or climbing the corporate ladder, and built places such as the U.S. Capitol building link social and physical hierarchies. In three experiments we examine the source and extent of these associations by testing whether people implicitly associate abstract social status indicators with concrete representations of spatial topography (level versus mountainous land) and relatively abstract representations of cardinal direction (south and north). Experiment 1 demonstrates speeded performance during an Implicit Association Test (IAT; Greenwald et al., 1998) when average social status is paired with level topography and high status with mountainous topography. Experiments 2 and 3 demonstrate a similar effect but with relatively abstract representations of cardinal direction (south and north), with speeded performance when average and powerful social status are paired with south and north coordinate space, respectively. Abstract concepts of social status are perceived and understood in an inherently spatial world, resulting in powerful associations between abstract social concepts and concrete and abstract notions of physical axes. These associations may prove influential in guiding daily judgments and actions.
Expanding NEURON’s Repertoire of Mechanisms with NMODL

Neuronal function involves the interaction of electrical and chemical signals that are distributed in time and space. The mechanisms that generate these signals and regulate their interactions are marked by a rich diversity of properties that precludes a "one size fits all" approach to modeling. This article presents a summary of how the model description language NMODL enables the neuronal simulation environment NEURON to accommodate these differences.
Conditional expression of a truncated fragment of nonmuscle myosin II-A alters cell shape but not cytokinesis in HeLa cells.

A truncated fragment of the nonmuscle myosin II-A heavy chain (NMHC II-A) lacking amino acids 1–591, ΔN592, was used to examine the cellular functions of this protein. Green fluorescent protein (GFP) was fused to the amino terminus of full-length human NMHC II-A, NMHC II-B, and ΔN592 and the fusion proteins were stably expressed in HeLa cells by using a conditional expression system requiring absence of doxycycline. The HeLa cell line studied normally expressed only NMHC II-A and not NMHC II-B protein. Confocal microscopy indicated that the GFP fusion proteins of full-length NMHC II-A, II-B, and ΔN592 were localized to stress fibers. However, in vitro assays showed that baculovirus-expressed ΔN592 did not bind to actin, suggesting that ΔN592 was localized to actin stress fibers through incorporation into endogenous myosin filaments. There was no evidence for the formation of heterodimers between the full-length endogenous nonmuscle myosin and truncated nonmuscle MHCs. Expression of ΔN592, but not full-length NMHC II-A or NMHC II-B, induced cell rounding with rearrangement of actin filaments and disappearance of focal adhesions. These cells returned to their normal morphology when expression of ΔN592 was repressed by addition of doxycycline. We also show that GFP-tagged full-length NMHC II-A or II-B, but not ΔN592, were localized to the cytokinetic ring during mitosis, indicating that, in vertebrates, the amino-terminus part of mammalian nonmuscle myosin II may be necessary for localization to the cytokinetic ring.
Physical properties of egg whites and whole eggs relevant to microwave pasteurization

Abstract Microwave pasteurization is a novel thermal processing technology in which non-uniform heating may be a major challenge. In this study, the suitability of using egg whites (EWs) and whole eggs (WEs) as model foods to evaluate the heating uniformity and to determine the cold and hot spots during microwave pasteurization was investigated. The samples were prepared from mixtures of water with commercial EW or WE powders at different solid concentrations (20%, 25%, 27.5%, and 30%) and salt contents (0, 50, 100, and 200 mM). Critical physical properties for desirable model food systems include appropriate dielectric properties, gelation temperatures, gel strengths, and water holding capacities (WHCs). The gelation temperature of liquid EW and WE were 70 and 80 °C; both fell in the pasteurization temperature range. At 915 MHz, the dielectric constants of liquid EW and WE samples and their heat induced gels decreased with solid concentration while the loss factor was not affected. Loss factors of liquid EW and WE samples increased linearly with salt addition, which could be explained by the linear increase of electrical conductivities by adding salt. The strength and WHC of heat induced EW and WE gels increased linearly with solid concentration, while salt addition had no significant effect. The results demonstrated the suitability of using EW and WE as model foods to determine the heating uniformity during microwave pasteurization process.
Tricks of the Trade: State Legislative Actions in School Finance Policy that Perpetuate Racial Disparities in the Post-Brown Era.

This article discusses the tricks of the trade that legislatures in formerly de jure segregated states might use to maintain racial funding disparities in existence before Brown and whether such ploys might be vulnerable to legal challenges. The first section provides an overview of modern school finance formulas and explains how legislatures in de jure segregated states might use state aid policies to produce racial funding disparities. The second section, through macrolevel, quantitative analyses, identifies those states where state aid is allocated such that minority populations are disadvantaged and where that disadvantage is subsequently reflected in total state and local revenue. The third section presents in‐depth case analyses of racial disparities in Kansas and Alabama that were identified through macrolevel analyses. The final section analyzes possible legal challenges that plaintiffs in those formerly de jure segregated states identified in our case analyses may bring to racially neutral state ...
Diminished functional activity of newly synthesized muscarinic acetylcholine receptors in stably transfected Y1 adrenal cells.

: We have examined the functional responsiveness of newly synthesized m2 muscarinic acetylcholine receptors in stably transfected Y1 adrenal cells. After inactivation of preexisting receptors with the covalent alkylating antagonist propylbenzilylcholine mustard, the number of cell surface receptors returned to control values over a 3-h period. After a 3-h recovery, the cells exhibited diminished sensitivity for muscarinic receptor-mediated inhibition of adenylyl cyclase activity, with much higher concentrations of agonist being required to elicit a response. The functional sensitivity returned to control values over a 12–18-h period. The decreased functional activity was not due to a decreased affinity of the newly synthesized receptors for agonist or to a decrease in the levels of inhibitory G proteins in the cells. The results suggest that muscarinic receptors may be synthesized in a form with diminished functional activity. The ability to study the maturation of receptor function in a transfected cell system should allow a combination of biochemical and molecular genetic approaches to analyze the synthesis and functional responsiveness of muscarinic receptors.
Disputes Over Coverage of Emergency Department Services: A Study of Two Health Maintenance Organizations

Abstract Study objective We describe the characteristics and outcomes of enrollee–health plan disputes over insurance coverage for emergency department (ED) services at 2 large health maintenance organizations (HMOs) that apply the prudent layperson standard. Methods We abstracted information from a stratified random sample of approximately 3,500 appeals of coverage denials lodged by privately insured enrollees between 1998 and 2000 at 2 of the nation's largest HMOs (hereafter referred to as Plan 1 and Plan 2). We describe appeals involving ED services in terms of the timing of visits, patient age, costs of services, primary reason the patient sought care, and appeal outcome. Results Disputes over ED services accounted for approximately one half (52%) of postservice appeals at Plan 1 and one third (34%) at Plan 2. Nearly one half (46%) of ED appeals involved weekend, nighttime, or holiday visits to the ED; 22% were children's visits. The average cost of services in dispute was US$1,107. The most common general reasons for the ED visits in dispute were symptoms of illness (64%), injuries (22%), and services related to disease (8%). The most common presenting symptoms were abdominal pain, cramps, or spasms (7.6%); earaches or ear infections (3.4%); and lacerations/cuts (2.9%). Enrollees won more than 90% of appeals. Conclusion The prevalence of ED cases among all appeals reflects disagreement between lay and expert judgments about what constitutes emergency care under the prudent layperson standard. The high rate at which enrollees win these appeals highlights significant disagreement in interpretation of the standard among different adjudicators within managed care organizations (medical groups and health plans). When enrollees fail to challenge denials that would be reversed on appeal, they bear the financial brunt of ambiguities in interpretation of the prudent layperson standard.
Extension of the labeled precursor method of measuring neurotransmitter kinetics to non-steady-state conditions: application to striatal dopamine metabolism.

: A solution of the differential equations describing the single open compartment model of neurotransmitter kinetics which does not assume a steady state is presented. In addition, a computer procedure is described for analyzing data obtained following the pulse injection of radiolabeled precursors, which eliminates the use of graphical methods in calculating fractional rate constants of synthesis and catabolism. This procedure also provides statistically valid estimates of the standard errors of the rate constants, allowing for tests of the significance of experimental effects. The ability of this approach to discriminate between changes in synthesis and catabolism under non-steadystate conditions is demonstrated by analyzing the kinetics of striatal dopamine metabolism following (a) administration of α-methyl-ρ-tyrosine and (b) lesion of the substantia nigra. The utility of this method and precautions in its use are discussed.
Die physiologischen Grundlagen des Verhaltens

Um unser Wissen uber das menschliche Verhalten erweitern zu konnen, mussen wir lernen, der Natur die richtigen Fragen zu stellen; dann mussen wir Methoden entwickeln, die Antworten auf diese Fragen geben, und zwar in einer Form, die mesbar und verstandlich ist.
Linking RNA Secondary Structure to the Free Energy of Tertiary Structure Folding through Coarse-Grained Models

The importance of RNA secondary structure to 3D structure has long been appreciated, but a quantitative understanding of the linkage between the two has remained unclear. Recent results from our labs have indicated that simple steric and connectivity properties of RNA secondary structure strongly constrain and bias the 3D conformations that are sampled by RNA junctions. To further investigate the significance of these so-called topological constraints we have performed extensive simulations of various cytosolic tRNAs (ctRNA), mitochondrial tRNAs (mtRNA), and variants of the hairpin ribozyme using a specialized coarse-grained molecular dynamics model. This model reduces RNAs to collections of semi-rigid helices linked by freely rotatable single strands and ignores attractive and electrostatic forces, thus isolating the effects of topological constraints on RNA structure. Our simulations reveal that secondary structure changes as small as the insertion or deletion of one nucleotide into a junction loop can significantly alter the entropic cost of folding due to changes in topological constraints. In the hairpin ribozyme, such single nucleotide changes modulate the tertiary structure folding free energy by ∼0.5 kcal/mol. More radical changes in junction topology alter folding free energies by >2 kcal/mol. These results are in strong agreement with previous experimental findings. In mtRNA, we show that a single nucleotide insertion, by altering topological constraints, causes a decrease in melting temperature of ∼10° C. This decreased melting temperature provides a possible mechanism for the pathogenicity of such mutations in humans. Together, our results indicate that simple topological constraints imposed by secondary structure are a powerful determinant of RNA 3D structure.
The Longevity of Memory CD8 T Cell Responses after Repetitive Antigen Stimulations

In experimental models in which the Ag-stimulation history of memory CD8 T cell populations was clearly defined (adoptive transfer of a known number of TCR-transgenic memory CD8 T cells), all facets of the ensuing CD8 T cell responses, including proliferative expansion, duration and extent of contraction, diversification of memory CD8 T cell transcriptomes, and life-long survival, were dependent on the number of prior Ag encounters. However, the extent to which sequential adoptive-transfer models reflect the physiological scenario in which memory CD8 T cells are generated by repetitive Ag challenges of individual hosts (no adoptive transfer involved) is not known. Direct comparison of endogenous memory CD8 T cell responses generated in repetitively infected hosts revealed that recurrent homologous boosting was required to preserve the numbers and increase the phenotypic and functional complexity of the developing memory CD8 T cell pool. Although life-long survival of the memory CD8 T cells was not impacted, phenotype (i.e., upregulation of CD62L) and function (i.e., homeostatic turnover, Ag-stimulated IL-2 production) of repeatedly stimulated memory CD8 T cells were dependent on time after last Ag encounter. Therefore, repetitive Ag challenges of individual hosts can substantially influence the numerical and functional attributes of polyclonal memory CD8 T cells, a notion with important implications for the design of future vaccination strategies aimed at increasing the number of protective memory CD8 T cells.
Do Not Be Stranded by Signals Not Perfectly Understood

The unfavorably resolved code was a gale That furrowed the hearts of even-keeled seamen. Beams broke, piercing the floating nightshift bulwark. Near silent, they ran on side, taking on necrologic water. Their ‘‘winding down’’ thoughts rowing home were laden With fruitless cargo, bedecked by sorrow and doubt. Damn, as we all butt through the channel of life The lighthouse periodically fails to whisper sweet dreams! Do not be stranded while seeking a far-heard whisper. His ribbed sea tides will touch only a few of our crafts.
Transmission Line Design for the Lunar Environment

This paper will exam how the mass, operating temperature, and efficiency of a transmission line operating on the moon is affected by its operating parameters, the lunar environment, and the choice of materials. The key transmission line parameters which have an effect on mass, operating temperature, and efficiency are voltage, power loss, and waveform. The choice of waveform for transmission will be influenced by the waveform of the source and load, and therefore an analysis of both dc and ac transmission is necessary for a complete understanding of lunar power transmission. The data presented is for the dc case only, however, the discussion of the environmental effects and of material selection are pertinent to both ac and dc transmission. Ac transmission is currently being studied and the resulting data with mass, volume, power loss, and operating temperature, the operating voltage is a key parameter in transmission line design and will be analyzed in detail. The role efficiency plays in transmission line design is also examined. The analyses include above and below the surface operation for both a vacuum-insulated, two-wire, transmission line, and a solid-dielectric-insulated, coaxial, transmission line.
HIGH-TECH SKILLS IN LOW-TECH HANDS: Issues of Advanced Practice and Collaborative Management

Abstract Nurse-midwifery practice has been defined by the American College of Nurse-Midwives (ACNM) as “the independent management of essentially normal newborns and women … occurring within a health care system which provides for medical consultation, collaborative management or referral. …” As the health care delivery system in the United States becomes increasingly complex and reliant on new forms of technology, it has become necessary to clarify roles and responsibilities for the nurse-midwife. In addition, mechanisms for acquiring new skills and for collaborating with physician colleagues must be well understood. A question frequently asked is where the boundaries of nurse-midwifery practice end and those of medical practice begin. Although practice scenarios vary for individual nurse-midwives and nurse-midwifery services, recent statements approved by the ACNM Board of Directors discuss these issues in an attempt to clarify the potentially confusing areas of collaboration and skill acquisition. This article explores the areas of expanded nurse-midwifery practice and collaborative management. Although individual clinical skills are not necessarily endorsed, a step-by-step approach that nurse-midwives can use for incorporation of new skills is presented. The concepts discussed will be a valuable tool to nurse-midwives in their practice.
Applying Jewish Law to New Circumstances

This chapter presents four sources in the Jewish tradition. It describes the death of Rabbi Hananyah ben Teradyon, the death of Rabbi Judah Hanasi, the Talmud's oft-repeated interpretation of "Love your neighbor as yourself" and the thirteenth-century text, Sefer Hasidim. The chapter suggests a methodology for applying Jewish law and the Jewish tradition generally to new moral issues. It views Jewish law as similar to a human being, with a body and a soul. The body of Jewish law, the corpus juris , functions in many of the ways that a human body does, with some parts changing rapidly and others very slowly in order to renew itself and accommodate itself to new environments. The law must be used with conscious attention to its foundations in Jewish theology and morality and its historical context to produce wise and appropriate as well as genuinely Jewish, moral guidance for us now. Keywords: corpus juris ; Jewish tradition; Rabbi Hananyah ben Teradyon; Rabbi Judah Hanasi; Sefer Hasidim
The Role of Tau in Neurodegenerative Diseases and Its Potential as a Therapeutic Target

The abnormal deposition of proteins in and around neurons is a common pathological feature of many neurodegenerative diseases. Among these pathological proteins, the microtubule-associated protein tau forms intraneuronal filaments in a spectrum of neurological disorders. The discovery that dominant mutations in the MAPT gene encoding tau are associated with familial frontotemporal dementia strongly supports abnormal tau protein as directly involved in disease pathogenesis. This and other evidence suggest that tau is a worthwhile target for the prevention or treatment of tau-associated neurodegenerative diseases, collectively called tauopathies. However, it is critical to understand the normal biological roles of tau, the specific molecular events that induce tau to become neurotoxic, the biochemical nature of pathogenic tau, the means by which pathogenic tau exerts neurotoxicity, and how tau pathology propagates. Based on known differences between normal and abnormal tau, a number of approaches have been taken toward the discovery of potential therapeutics. Key questions still remain open, such as the nature of the connection between the amyloid-β protein of Alzheimer's disease and tau pathology. Answers to these questions should help better understand the nature of tauopathies and may also reveal new therapeutic targets and strategies.
Concurrent Obesity, Diabetes, and Steatosis Increase Risk of Advanced Fibrosis Among HCV Patients: A Systematic Review

Rising rates of obesity, diabetes mellitus (DM), and nonalcoholic fatty liver disease among patients with chronic hepatitis C virus infection (HCV) may contribute to more rapid disease progression. To evaluate the impact of concurrent obesity, DM, and steatosis on disease progression among HCV patients. A systematic review using structured keyword search of MEDLINE and EMBASE from January 1, 2001, to July 1, 2014, was performed to identify original articles evaluating the association of obesity, DM, and steatosis with advanced fibrosis (AF) among adults with chronic HCV. Studies involving HCV patients coinfected with human immunodeficiency virus, hepatitis B virus, hepatocellular carcinoma, or other chronic liver diseases were excluded. Quality assessment utilized Newcastle–Ottawa Scale. Twenty cohort studies met inclusion criteria for analyses. Obesity was associated with increased risk of AF in seven studies with effect size ranging from OR 1.08 to 7.69. However, four studies did not demonstrate a significant association between obesity and AF. The presence of advanced steatosis among HCV patients was associated with increased risk of AF in 12 studies (OR 1.80–14.3). Concurrent DM was associated with increased risk of AF in six studies (OR 2.25–9.24). Thirteen studies were good quality, and seven studies were fair quality. Concurrent DM and steatosis are associated with increased risk of AF among chronic HCV patients. The majority of studies demonstrated significant associations of obesity with AF. Targeted interventions to optimize management of obesity-related diseases among HCV patients may help mitigate HCV disease progression.
Being Forgiven: Toward a Thicker Description of Forgiveness:

The author describes the less frequently examined process of seeking forgiveness from others. Examples from the seminary classroom are used to describe the process. The examination of the seeking forgiveness process provides insight into the whole construct of forgiveness.
Secondary Hemophagocytic Lymphohistiocytoisis (HLH) in Adults Patients

S76 Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Lymphoma, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Veterinary Medicine & Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX
Severe Hand Osteoarthritis Strongly Correlates With Major Joint Involvement and Surgical Intervention.

Abstract Background The presence of hand osteoarthritis (OA) increases the risk for developing OA in other major joints. Although genetic predisposition has been implicated in its causation, its exact role has yet to be established. The association of hand OA with symptomatic and asymptomatic major joints has not been previously studied. Methods Hundred consecutive patients had a hand photo taken for visual documentation of the hand joints. Radiographs of hand and all major symptomatic joints were analyzed and classified using the Kellgren-Lawrence scale by 2 independent observers including an orthopedic radiologist. Results Severe hand OA was present in 91% of the patients. Radiographic analysis showed that the hip was involved in 88% of the patients, of whom 85.2% (75) were symptomatic and 14.7% (13) were asymptomatic. Hip arthroplasty was required by 62.5% (55) of symptomatic hip patients. Knee involvement was present in 37% of the patients; all were symptomatic and 81.1% (30) of these required knee arthroplasty. Bilateral surgery was performed in 33% (28) and "2 joint (hip and knee)" surgery was performed in 6% (5). Spine involvement was present in 72% of the patients. There was a significant correlation between hand radiographic findings of OA and hip ( r = 0.68; P = .03), knee ( r = 0.58; P = .042), and spine ( r = .39; P = .05) involvement. Conclusion There was a significant correlation between severe hand OA and hip, knee, and spine involvement. Severity of Hand OA can have a predictive value on multiple joint involvement and risk of surgical intervention. This study emphasizes the need to investigate the genetic predisposition in causation of OA.
The Drops that Carve the Stone: State and Manufacturer Responsibility for the Humanitarian Impact of Cluster Munitions and Explosive Remnants of War

This paper addresses basic legal principles of state responsibility for internationally wrongful acts and how cluster munitions fit into that framework. It then lays out the reasons for ratifying Protocol V on Explosive Remnants of War of the Convention on Certain Conventional Weapons (CCW). The article goes on to argue that another international protocol specifically addressing cluster munitions is needed to clarify international humanitarian law by giving greater emphasis to humanitarian concerns. Finally suggestions are made or actions that can be taken at the national and bi-lateral level to curtail cluster munition use.
Natural Gas and Cellulosic Biomass: A Clean Fuel Combination? Determining the Natural Gas Blending Wall in Biofuel Production

Natural gas has the potential to increase the biofuel production output by combining gas- and biomass-to-liquids (GBTL) processes followed by naphtha and diesel fuel synthesis via Fischer-Tropsch (FT). This study reflects on the use of commercial-ready configurations of GBTL technologies and the environmental impact of enhancing biofuels with natural gas. The autothermal and steam-methane reforming processes for natural gas conversion and the gasification of biomass for FT fuel synthesis are modeled to estimate system well-to-wheel emissions and compare them to limits established by U.S. renewable fuel mandates. We show that natural gas can enhance FT biofuel production by reducing the need for water-gas shift (WGS) of biomass-derived syngas to achieve appropriate H2/CO ratios. Specifically, fuel yields are increased from less than 60 gallons per ton to over 100 gallons per ton with increasing natural gas input. However, GBTL facilities would need to limit natural gas use to less than 19.1% on a LHV energy basis (7.83 wt %) to avoid exceeding the emissions limits established by the Renewable Fuels Standard (RFS2) for clean, advanced biofuels. This effectively constitutes a blending limit that constrains the use of natural gas for enhancing the biomass-to-liquids (BTL) process.
A Layered View of Shape Perception

ABSTRACTThis article develops a view of shape representation both in visual experience and in subpersonal visual processing. The view is that, in both cases, shape is represented in a ‘layered’ man...
Evidence for Sexual Dimorphism in the Early Miocene Palaeothentid Acdestis owenii (Marsupialia: Paucituberculata)

Abstract. Although sexual size dimorphism is an important component of the biology of many living New World metatherians, little is known about sexual dimorphism in extinct members of this group. Here, we describe morphometric variation in two traditionally recognized species of the paucituberculatan Acdestis from the early Miocene Santa Cruz Formation of Patagonia, A. owenii and A. spegazzinii (=A. lemairei). The results of this morphometric study show that specimens of Acdestis from the Santa Cruz Formation form a single morphological continuum, with no features that clearly distinguish the two recognized morphotypes besides overall body size and the depth of the mandibular ramus, both features which are sexually variable in extant marsupials. This suggests that the two species of Acdestis from the Santa Cruz Formation are better regarded as gender morphs of a single dimorphic species rather than two highly similar monomorphic species. The degree of sexual dimorphism inferred here for Acdestis is compar...