cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulation of chronic lung inflammation to house dust mite allergen by Wnt antagonist (CAM1P.144)

Recruitment of leukocytes in response to allergen is an important step in the initiation of airway inflammation. Here we demonstrate that the Wnt antagonist Dkk-1 regulates the formation of leukocyte-platelet aggregates (LPAs) following house dust mite (HDM) allergen challenge. We show that circulating Dkk-1 is elevated after recurrent HDM allergen challenges and the source is activated platelets. The increase of P-selectin glycoprotein ligand-1 (PSGL-1) expression in leukocytes was mediated by Dkk-1 while other cell adhesion molecules such as ICAM-1 or LFA-1 were only marginally affected. The formation of LPAs was markedly reduced in Dkk-1 hypomorphic doubleridge (Dkk-1d/d) mice that had a 90% reduction of circulating Dkk-1. Recurrent allergen challenges in Dkk-1d/d mice showed significantly reduced infiltration of leukocytes including neutrophils in the lung compared to wildtype mice. Importantly, we show that type 2 cytokines (e.g. IL-4, IL-5 and IL-13) from CD4 T cells in mediastinal lymph nodes (med LNs) of Dkk-1d/d mice were substantially reduced compared to wildtype mice following allergen exposure. Consistently, we observed Gata-3 and c-Maf induction in Th2 cells did not occur in med LN CD4 T cells from Dkk-1d/d mice. Therefore, our results demonstrate that the Wnt antagonist from activated platelets regulates the early stage of leukocyte infiltration in the challenged tissue, thereby regulating inflammation and type 2 immune responses.
The impacts of dynamic façade shading typologies on building energy performance and occupant’s multi-comfort

ABSTRACTDespite a growing interest in dynamic facades shading systems, few studies have measured their actual performance in the field using full-scale prototypes or evaluated their performance in a comparative way. This paper reports on an important yet understudied topic related to comparing the performance of different dynamic shading typologies and assessing their impacts on building energy savings, daylighting distribution, glare control, and solar insolation management for a typical office space in ASHRAE Climate Zone 4C. Results show variations in performance across the dynamic shading typologies studied. While some systems show superior performance in reducing solar loads and building energy consumption, other typologies studied performed better in managing glare and providing better spatial daylight autonomy. The paper concludes with a framework for the parametric design and assessment of dynamic shade systems based on their performance and climatic suitability for the main eight ASHRAE’s climate...
Edge Exchangeable Models for Interaction Networks

AbstractMany modern network datasets arise from processes of interactions in a population, such as phone calls, email exchanges, co-authorships, and professional collaborations. In such interaction networks, the edges comprise the fundamental statistical units, making a framework for edge-labeled networks more appropriate for statistical analysis. In this context we initiate the study of edge exchangeable network models and explore its basic statistical properties. Several theoretical and practical features make edge exchangeable models better suited to many applications in network analysis than more common vertex-centric approaches. In particular, edge exchangeable models allow for sparse structure and power law degree distributions, both of which are widely observed empirical properties that cannot be handled naturally by more conventional approaches. Our discussion culminates in the Hollywood model, which we identify here as the canonical family of edge exchangeable distributions. The Hollywood model i...
A comparison of two stage-based hybrid algorithms for a batch scheduling problem in hybrid flow shop with learning effect

Abstract This paper addresses the hybrid flow shop batch scheduling problem with sequence- and machine-dependent family setup times where the objective is to simultaneously minimize the weighted sum of the total weighted completion time and total weighted tardiness, being mindful of the producer and customers, respectively. In order to reflect the industry requirements, machine availability times, job release times, machine capability and eligibility for processing jobs, stage skipping, and learning effect are considered. Unlike group scheduling, batch scheduling disregards the group technology assumptions by splitting pre-determined groups of jobs into inconsistent batches to perform timely processing of jobs with higher priority and utilize the maximum available capacity of the machines. One of the contributions of this research is to realize the benefits of integrating the batching decision into the group scheduling approach. Another contribution is to develop robust meta-heuristics based on hybridization of local search and population-based structures along with the stage-based interdependency strategy to solve the research problem. An initial solution finding mechanism and a comprehensive data generation mechanism are developed. The efficiency and effectiveness of the meta-heuristic algorithms are verified by lower bounds obtained by two mixed-integer linear programming models. The benefits of considering the batching decision with respect to desired lower bounds on batch sizes will hopefully encourage practitioners to apply the batch scheduling approach instead of the group scheduling approach.
Fractionation of Complex Protein Mixtures by Liquid-Phase Isoelectric Focusing

Protein fractionation is essential to uncovering low-abundance proteins in complex protein mixtures. Many common methods and techniques are used to fractionate proteins, including chromatography (size exclusion, affinity, ion exchange, etc.), electrophoresis, and solution chemistry. Regardless of the method employed, the ultimate goal of protein fractionation is to enable more protein analysis by today's current proteomics technologies, such as one- (1-DGE) or two-dimensional gel electrophoresis (2-DGE) and liquid-chromatography and tandem mass spectrometry (LC-MS/MS).The MicroRotofor isoelectric focusing (IEF) cell fractionates proteins in free solution according to their isoelectric point (pI). We demonstrate the ability of the MicroRotofor to enrich low-abundance proteins in mouse brain tissue, thus enabling further identification of potential biomarker candidates.
Physician responsibility for patients' quality of life.

Physicians have an obligation to consider a patient's quality of life when making treatment decisions and should consider giving patients the options of withholding or withdrawing aggressive treatment if that treatment will not restore the kind of life the patient finds meaningful. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
Hydrogen Bond Surrogate Stabilization of β-Hairpins

Peptide secondary and tertiary structure motifs frequently serve as inspiration for the development of protein–protein interaction (PPI) inhibitors. While a wide variety of strategies have been used to stabilize or imitate α-helices, similar strategies for β-sheet stabilization are more limited. Synthetic scaffolds that stabilize reverse turns and cross-strand interactions have provided important insights into β-sheet stability and folding. However, these templates occupy regions of the β-sheet that might impact the β-sheet’s ability to bind at a PPI interface. Here, we present the hydrogen bond surrogate (HBS) approach for stabilization of β-hairpin peptides. The HBS linkage replaces a cross-strand hydrogen bond with a covalent linkage, conferring significant conformational and proteolytic resistance. Importantly, this approach introduces the stabilizing linkage in the buried β-sheet interior, retains all side chains for further functionalization, and allows efficient solid-phase macrocyclization. We ant...
Enhancing the teaching of elastic buckling using additive manufacturing

Abstract This is the third part in a trilogy of papers examining ways in which additive manufacturing can be used to facilitate the introduction of basic principles in structural analysis. Each paper uses 3D-printing and simple, but non-trivial, slender geometric forms, to provide a hands-on aspect to structural behavior in which flexure plays a dominant role. The first part dealt with linear structural analysis (Virgin, 2017), extended to dynamics and vibration in the second part (Virgin, 2017). The current paper focuses on slender structures in which compressive axial loading is the new ingredient and hence buckling becomes a central issue. This has similarities and differences with the two previous papers, but in all instances the role played by relatively high-precision 3D-printing opens the door to versatile and effective illustration, and the development of a deeper appreciation of structural phenomena.
A Survey of the Shi Arrangement

In [58], Shi proved Lusztig’s conjecture that the number of two-sided cells for the affine Weyl group of type \(A_{n-1}\) is the number of partitions of n. As a byproduct, he introduced the Shi arrangement of hyperplanes and found a few of its remarkable properties. The Shi arrangement has since become a central object in algebraic combinatorics. This article is intended to be a fairly gentle introduction to the Shi arrangement, intended for readers with a modest background in combinatorics, algebra, and Euclidean geometry.
TP3-2 Epilepsy surgery outcomes in a paediatric population – a single centre 10 year experience

Objectives To analyse the efficacy of epilepsy surgery in reducing the burden of seizures in a paediatric population – a single centre 10 year experience. Design Single centre retrospective review of medical records. Subjects 74 consecutive paediatric patients who underwent epilepsy surgery between 2008–2017 by one neurosurgeon at a single centre. Methods Seizure history, pre-operative investigations, surgical interventions, seizure outcomes, complications and long term anti-epileptic drug (AED) use were evaluated. Seizure outcomes at 1 year post surgery to the last available follow up (up to 5 years) were documented and classified using the Engel System. Engel I and II were classified as a good seizure outcome and Engel III and IV were classified as a poor seizure outcome. Results The mean duration of follow up was 41 months. 62.2% of patients achieved seizure freedom (Engel I) at their latest follow up, with 82.4% of patients achieving a good seizure outcome (Engel I/II). 13.5% of patients achieved worthwhile improvement (Engel III) and only 4.1% of patients had no worthwhile improvement in seizure burden (Engel IV). More favourable outcomes were observed in children with temporal lobe epilepsy. Post-surgery AED use was reduced or discontinued in 41.4% of all patients; 41.4% of the 29 patients with AED data at their 5 year follow up were completely free of AEDs. Conclusions Epilepsy surgery is an efficacious treatment with low morbidity and no mortality that is underutilised in children with medically intractable seizures.
How Transient is Prison Life? An Examination of Transfers and Their Heterogeneity

Prison scholarship suggests that individuals’ experiences during incarceration are diverse and contribute to the impacts of a prison sentence. This article seeks to advance this line of theory and ...
Performance of asynchronous optimized Schwarz with one-sided communication

Abstract In asynchronous iterative methods on distributed-memory computers, processes update their local solutions using data from other processes without an implicit or explicit global synchronization that corresponds to advancing the global iteration counter. In this work, we test the asynchronous optimized Schwarz domain-decomposition iterative method using various one-sided (remote direct memory access) communication schemes with passive target completion. The results show that when one-sided communication is well-supported, the asynchronous version of optimized Schwarz can outperform the synchronous version even for perfectly balanced partitionings of the problem on a supercomputer with uniform nodes.
U-NSGA-III: A Unified Evolutionary Optimization Procedure for Single, Multiple, and Many Objectives: Proof-of-Principle Results

Evolutionary algorithms (EAs) have been systematically developed to solve mono-objective, multi-objective and many-objective problems, respectively, over the past few decades. Despite some efforts in unifying different types of mono-objective evolutionary and non-evolutionary algorithms, there does not exist too many studies to unify all three types of optimization problems together. In this study, we propose an unified evolutionary optimization algorithm U-NSGA-III, based on recently-proposed NSGA-III procedure for solving all three classes of problems. The \(\text{ U-NSGA-III }\) algorithm degenerates to an equivalent and efficient population-based optimization procedure for each class, just from the description of the number of specified objectives of a problem. The algorithm works with usual EA parameters and no additional tunable parameters are needed. The performance of \(\text{ U-NSGA-III }\) is compared with a real-coded genetic algorithm for mono-objective problems, with NSGA-II for two-objective problems, and with NSGA-III for three or more objective problems. Results amply demonstrate the merit of our proposed unified approach, encourage its further application, and motivate similar studies for a richer understanding of the development of optimization algorithms.
Control of Parametric Games

This work studies a class of multi-player games in which the players' decisions can be influenced by a superplayer. We define a game with $n$ players and parameterized utilities $u$ (., a) where the superplayer controls the value of a. The regular players follow Markovian repeated play dynamics that encompass a wide class of learning dynamics including strict best response. The objective of the superplayer is to control $a$ dynamically to achieve a desired outcome in the game-play, which in this work we define as the realization of target joint strategies. We introduce the class of parametric games and reformulate the superplayer control problem as a Markov decision process (MDP). Reachability criteria are developed, allowing the superplayer to determine which game-play may occur with positive probability. With a reachable goal joint strategy, a cost-optimal policy can be computed using standard tools in dynamic programming. A sample MDP reward function is presented such that a reachable target joint strategy is guaranteed to be played almost surely. Finally, an application in a cyber-security context is provided to illustrate the use of the proposed methodology and its effectiveness.
Predicting Hospital Readmissions from Home Healthcare in Medicare Beneficiaries

Objective To use patient-level clinical variables to develop and validate a parsimonious model to predict hospital readmissions from home healthcare (HHC) in Medicare fee-for-service beneficiaries. Design Retrospective analysis using multivariable logistic regression and gradient boosting machine (GBM) learning to develop and validate a predictive model. Setting/participants/meaurements A 5% national sample of patients, aged 65 years or older, with Medicare fee-for-service who received skilled HHC services within 5 days of hospital discharge in 2012 (n = 43 407). Multiple data sets were merged, including Medicare Outcome and Assessment Information Set, Home Health Claims, Medicare Provider Analysis and Review, and Master Beneficiary Summary Files, to extract patient-level variables from the first HHC visit after discharge and measure 30-day readmission outcomes. Results Among 43 407 patients with inpatient hospitalizations followed by HHC, 14.7% were readmitted within 30 days. Of the 53 candidate variables, seven remained in the final model as individually predictive of outcome: Elixhauser comorbidity index, index hospital length of stay, urinary catheter presence, patient status (ie, fragile health with high risk of complications or serious progressive condition), two or more hospitalizations in prior year, pressure injury risk or presence, and surgical wound presence. Of interest, surgical wounds, either from a total hip or total knee arthroplasty procedure or another surgical procedure, were associated with fewer readmissions. The optimism-corrected c-statistics for the full model and parsimonious model were 0.67 and 0.66, respectively, indicating fair discrimination. The Brier score for both models was 0.120, indicating good calibration. The GBM model identified similar predictive variables. Conclusion Variables available to HHC clinicians at the first postdischarge HHC visit can predict readmission risk and inform care plans in HHC. Future analyses incorporating measures of social determinants of health, such as housing instability or social support, have the potential to enhance prediction of this outcome. J Am Geriatr Soc 67:2505-2510, 2019.
The reciprocal impacts of adversity and personality traits: A prospective longitudinal study of growth, change, and the power of personality.

Objective We integrate the study of post-traumatic growth with personality science by examining the reciprocal effects of adversity and core personality traits. We implemented conceptual (i.e., incorporating personality traits into the study of adversity-related growth, examining trait-specific and configural personality change, and adopting a cumulative approach to adversity) and methodological (i.e., three-wave prospective design, assessing many life events, sampling from populations likely to experience adversity) innovations to advance the study of personality development and of the generality of adversity-related growth. Method A diverse sample (41% nonwhite, 48% low-income, 68% female, Mage = 44, 30% diagnosed with Borderline Personality Disorder) participated in a three-wave prospective longitudinal study (N = 258-128 across waves). Participants completed a personality inventory and a battery of life-event surveys (including 105 events) at each wave. Results Personality was generally stable from trait-specific and configural perspectives, and all traits were correlated with adversity. All traits, particularly Extraversion and Conscientiousness, predicted adversity. Adversity predicted increases in Emotionality and decreases in Agreeableness. Conclusions Although personality growth is not the typical response to adversity within a 3-year period, findings underscore the real-world impact of personality, and they provide some support for developmental theories emphasizing the effects of life events.
Is Hysterectomy a Risk Factor for Urinary Retention? A Retrospective Matched Case Control Study.

ABSTRACT Study objective Compare the rates of urinary retention in patients undergoing endoscopic hysterectomy with those of patients undergoing nonhysterectomy endoscopic gynecologic surgery. Design Retrospective case control study matched by operative time. Setting Academic medical center. Patients All patients undergoing endoscopic gynecologic surgeries between January 2013 and December 2018. Interventions Outpatient endoscopic gynecologic surgery. Measurements and Main Results A total of 200 endoscopic hysterectomy cases were matched to endoscopic nonhysterectomy gynecologic surgery controls in a 1:1 ratio. The differences in baseline and operative characteristics between the 2 groups included age (48.6 years vs 45.7 years, p = .04), perioperative opioid administration (morphine milligram equivalents, 11.6 mg vs 7.6 mg, p = .01), and estimated blood loss (64.1 mL vs 31.8 mL, p = .001). The rate of urinary retention in the hysterectomy group was double that in the nonhysterectomy group (26.5% vs 13%, p = .01). In the hysterectomy group, age, perioperative opioids, operative time, and estimated blood loss did not differ between those who failed and those who passed the void trial. In the nonhysterectomy group, only operative time was significantly longer in those who failed the void trial (108 minutes vs 94.3 minutes, p = .04). After adjusting for perioperative opioid use and operative time, the relative risk of urinary retention in the hysterectomy group was 2.3 (p = .002, 95% confidence interval, 1.38–3.98). Conclusion Hysterectomy appears to be an independent and major factor contributing to postoperative urinary retention. When compared with nonhysterectomy gynecologic surgical controls with similar operative times, the rate of urinary retention in patients who underwent hysterectomy was doubled.
The ancient fusogen EnvP(b)1 is expressed in human tissues and its structure informs the evolution of gammaretrovirus envelope proteins

ABSTRACT Host genomes have acquired diversity from viruses through the capture of viral elements, often from endogenous retroviruses (ERVs). These viral elements contribute new transcriptional control elements and new protein encoding genes, and their refinement through evolution can generate novel physiological functions for the host. EnvP(b)1 is an endogenous retroviral envelope gene found in human and other primate genomes. We show that EnvP(b)1 arose very early in the evolution of primates, i.e. at least 40-47 million years ago, but has nevertheless retained its ability to fuse primate cells. We have detected similar sequences in the genome of a lemur species, suggesting that a progenitor virus may have circulated 55+ million years ago. We demonstrate that EnvP(b)1 protein is expressed in multiple human tissues and is fully processed, rendering it competent to fuse cells. This activated fusogen is expressed in multiple healthy human tissues and is under purifying selection, suggesting that its expression is selectively advantageous. We determined a structure of the inferred receptor binding domain of human EnvP(b)1, revealing close structural similarities between this Env protein and those of currently circulating leukemia viruses, despite poor sequence conservation. This observation highlights a common scaffold from which novel receptor binding specificities have evolved. The evolutionary plasticity of this domain may underlie the diversity of related Envs in circulating viruses and coopted elements alike. The function of EnvP(b)1 in primates remains unknown. SIGNIFICANCE STATEMENT Organisms can access genetic and functional novelty by capturing viral elements within their genomes, where they can evolve to drive new cellular or organismal processes. We demonstrate that a retrovirus envelope gene, EnvP(b)1, has been maintained as a functional protein for 40 to ≥55 million years and is expressed as a protein in multiple healthy human tissues. We believe it has an unknown function in primates. We determined the structure of its inferred receptor binding domain and compared it with the same domain in modern viruses. We find a common conserved architecture that underlies the varied receptor binding activity of divergent Env genes. The modularity and versatility of this domain may underpin the evolutionary success of this clade of fusogens.
Chapter 31 – Human Rights

Human rights impact on the lives of all those living and working in the United Kingdom, and it is vitally important that community pharmacists have a good understanding of the relevant principles which apply to their dealings with members of the general public. A patient’s right to privacy is the major area with which a community pharmacist is likely to engage.
Inositol and Hepatic Lipidosis. II. Effect of Inositol Supplementation and Time from Parturition on Serum Insulin, Thyroxine and Triiodothyronine and Their Relationship to Serum and Liver Lipids in Dairy Cows

Percutaneous liver biopsies and blood samples were obtained from 80 dairy cows in nine Michigan herds over the peripartum period. Thirty-nine cows were fed 17 g of supplemental inositol and 41 were fed a placebo. Liver biopsies were assayed for total myoinositol and triglyceride (TG) concentrations. Blood samples were assayed for serum dextran precipitable cholesterol, nonesterified fatty acids (NEFA), insulin, thyroxine (T4), free (FT4), triiodothyronine (T3) and free T3 (FT3) concentrations. Serum concentrations of insulin and the thyroid hormones decreased near parturition, with lowest concentrations occurring in the immediate postpartum period. Concentrations of T3 correlated well with T4, and the concentrations of free thyroid hormones reflected concentrations of total thyroid hormones. The percentage of hormone in the free fraction remained constant over time. Serum insulin, T3 and T4 were negatively correlated with serum NEFA and liver TG concentrations. Thyroid hormone concentrations were positively correlated with serum dextran precipitable cholesterol concentrations. Inositol supplementation was associated with reduced circulating T3 and FT3 concentrations, but not T4 and FT4 concentrations. Changes in hormone concentrations at parturition and their relationship to liver TG and serum NEFA concentrations were consistent with a metabolic adaptation by the dairy cow to the negative energy balance of early lactation.
Obtaining the Charter for Connecticut and Election to the Royal Society of London

After the restoration of Charles II, John Winthrop, the Younger, traveled to London to obtain a Royal Charter for Connecticut. While it took a long time and required a large sum of money, Winthrop showed both political skill and patience in obtaining his desired end. He also used his copious free time in London to pursue his scientific interests among the Hartib Circle. He even became a founding member of the Royal Society. A brief discussion of the contributions to chemistry in 17th century New England by Cotton Mather is also presented.
What is the role of the cingulate cortex in pain

Pain is a complex experience that is perceived as signaling potential danger and has sensory-discriminative, emotional, motivational, and behavioral components. Consistent with its complexity, pain activates several brain areas that form part of distributed networks. The cingulate cortex is a major hub in many of these networks and has a critical role in several aspects of pain processing.1 Functional neuroimaging studies in humans indicate that emotional, cognitive, and motor responses to pain involve different portions of the cingulate cortex.2–4 Studies in mouse models show that areas of the cingulate cortex undergo profound plastic changes in structure and synaptic function in the setting of acute and chronic pain.5,6 The cingulate cortex thus provides a target for neuromodulation using deep brain stimulation (DBS).7
Uniting green criminology and earth jurisprudence: by J. Lampkin, London and New York, Routledge, 2020, 100 pp., $59.95 (paperback), (ebook), ISBN 0367613069

Environmental degradation caused by human action constitutes a severe threat to the health of the entire global ecosystem. We therefore need to dedicate our attention to finding suitable frameworks...
Historia, novela y teatro. La representación del indígena en dos obras literarias de Alcides Greca

The aim of this article is to analise the construction of visions regarding the image of indigenous people in the first half of the twentieth century, with a focus on the context of the mocovi aborigines in the town of San Javier (province of Santa Fe, Argentina). In order to do so, we will consider two literary works by the well-known politician, jurist and writer Alcides Greca (San Javier, 1889 – Rosario, 1956), who referred several times to the native people of his own region and especially to the rebellion led by them in 1904. The object of our analysis will be the vision of the indigenous conflict reflected in those pieces and its relation with the context of their production, trying to see through them different aspects of the ideology and the society of their time.
Energy performance of control strategies for smart glazed windows applied to office buildings

Abstract This paper presents a systematic analysis for the energy performance of control strategies specific to smart glazed windows when applied to office spaces. In particular, the energy efficiency benefits of rule-based and optimized controls to operate smart glazing are evaluated for office spaces. Several rule-based control strategies are considered to operate smart glazed windows including those that switch to specific tint levels using measurable environmental parameters such as outdoor ambient air temperatures as well as direct and total solar radiations. In addition, the analysis evaluates optimal controls that minimize the total energy consumption for the office space with and without daylighting capabilities using hourly, daily, or monthly switching frequencies. The results of various sensitivity analyses indicate that optimized controls perform generally better than rule-based controls even when their threshold settings are adequately selected. However, the performance of rule-based controls can be substantially enhanced when optimal threshold settings are used to switch between various smart glazing tint states. These optimal switching settings depend on various factors including the type of smart glazing used as well as orientation and size of the windows and the location of the office space. Moreover, the analysis indicates that optimized hourly settings provide higher energy savings than any other control strategy with reduction of annual energy consumption of the office spaces reaching up to 20% relative to static glazing.
Analysis and Management of Microarray Gene Expression Data

Microarray experiments require careful planning and choice of analysis tools in order to get the most out of the data generated, especially considering the associated significant cost and effort. Microarray experiments also require careful documentation, often residing in local databases and/or submitted to public repositories. An often bewildering assortment of choices is available for experimental design, data preprocessing, data analysis (e.g., differential gene expression, classification), and data management. This unit covers the basic steps and common applications for planning, data processing, and data management of microarray experiments, and provides guidance to making choices based on the goals and practical realities of the experiment, as well as the authors' experience in this area. Keywords: microarray; experimental design; data preprocessing; data analysis; databases; gene expression
Topological Behavior of Plasmid DNA

The discovery of the B-form structure of DNA by Watson and Crick led to an explosion of research on nucleic acids in the fields of biochemistry, biophysics, and genetics. Powerful techniques were developed to reveal a myriad of different structural conformations that change B-DNA as it is transcribed, replicated, and recombined and as sister chromosomes are moved into new daughter cell compartments during cell division. This article links the original discoveries of superhelical structure and molecular topology to non-B form DNA structure and contemporary biochemical and biophysical techniques. The emphasis is on the power of plasmids for studying DNA structure and function. The conditions that trigger the formation of alternative DNA structures such as left-handed Z-DNA, inter- and intra-molecular triplexes, triple-stranded DNA, and linked catenanes and hemicatenanes are explained. The DNA dynamics and topological issues are detailed for stalled replication forks and for torsional and structural changes on DNA in front of and behind a transcription complex and a replisome. The complex and interconnected roles of topoisomerases and abundant small nucleoid association proteins are explained. And methods are described for comparing in vivo and in vitro reactions to probe and understand the temporal pathways of DNA and chromosome chemistry that occur inside living cells.
Equivalent Mass versus Life Cycle Cost for Life Support Technology Selection

The decision to develop a particular life support technology or to select it for flight usually depends on the cost to develop and fly it. Other criteria such as performance, safety, reliability, crew time, and technical and schedule risk are considered, but cost is always an important factor. Because launch cost would account for much of the cost of a future planetary mission, and because launch cost is directly proportional to the mass launched, equivalent mass has been used instead of cost to select advanced life support technology. The equivalent mass of a life support system includes the estimated mass of the hardware and of the spacecraft pressurized volume, power supply, and cooling system that the hardware requires. The equivalent mass of a system is defined as the total payload launch mass needed to provide and support the system. An extension of equivalent mass, Equivalent System Mass (ESM), has been established for use in the Advanced Life Support project. ESM adds a mass-equivalent of crew time and possibly other cost factors to equivalent mass. Traditional equivalent mass is strictly based on flown mass and reflects only the launch cost. ESM includes other important cost factors, but it complicates the simple flown mass definition of equivalent mass by adding a non-physical mass penalty for crew time that may exceed the actual flown mass. Equivalent mass is used only in life support analysis. Life Cycle Cost (LCC) is much more commonly used. LCC includes DDT&E, launch, and operations costs. For Earth orbit rather than planetary missions, the launch cost is less than the cost of Design, Development, Test, and Evaluation (DDTBE). LCC is a more inclusive cost estimator than equivalent mass. The relative costs of development, launch, and operations vary depending on the mission destination and duration. Since DDTBE or operations may cost more than launch, LCC gives a more accurate relative cost ranking than equivalent mass. To select the lowest cost technology for a particular application we should use LCC rather than equivalent mass.
Evaluation of step interpolation of systolic arterial blood pressure signals

Power spectral analysis of systolic arterial blood pressure variability (SAPV) provides a window to the activity of the autonomic nervous system when used in conjunction with heart rate variability (HRV) spectral techniques. To derive power spectra from raw blood pressure signals, many steps of signal processing must be performed. Most popular methods of spectral analysis such as the FFT require evenly spaced samples; therefore interpolation and resampling techniques must be used. Since various resampling techniques introduce biasing to resulting spectra, it was determined that when comparing HRV spectra to SAPV spectra, the same interpolation methods should be used for both. It was found that step interpolation of systolic blood pressures results in spectra that are similar in content to that of the corresponding raw blood pressure signal due to the inclusion of HRV components.
Comparison of a Ground-based Microlensing Search for Planets with a Search from Space

We compare a space-based microlensing search for planets with a ground-based microlensing search originally proposed by D. Tytler. Perturbations of microlensing light curves when the lens star has a planetary companion are sought by one wide-angle survey telescope and an array of three or four follow-up narrow-angle telescopes distributed in longitude that follow events with high-precision, high time resolution photometry. Alternative ground-based programs are considered briefly. With the four 2 m telescopes distributed in longitude in the Southern Hemisphere in the Tytler proposal, observational constraints on a ground-based search for planets during microlensing events toward the center of the Galaxy are severe. Probably fewer than 100 events could be monitored per year with high-precision, high time resolution photometry, with only about 42% coverage on the average regardless of how many events were discovered by the survey telescope. Statistics for the occurrence and properties for Jupiter-mass planets would be meaningful but relatively meager 4 years after the program was started, and meaningful statistics for Earth-mass planets would be nonexistent. In contrast, the 14,500 events in a proposed 4 year space-based program (the Galactic Exoplanet Survey Telescope) would yield very sound statistics on the occurrence, masses, and separations of Jupiter-mass planets, and significant constraints on similar properties for Earth-mass planets. The significance of the Jupiter statistics would be to establish the frequency of planetary systems like our own, where terrestrial planets could exist inside the orbits of the giants.
DECISIONS, ERROR AND HETEROGENEITY

Probabilistic choices or ‘choice errors’ may play an important supporting role in shaping observed risky choices, and a variety of restrictions on such choice probabilities play the role of identifying restrictions in empirical decision research. We test six restrictions in the context of common ratio effect data for a general class of theories of risky choice. Two restrictions, one for aggregate and one for individual data, are supported. But none of the heterogeneity restrictions that make the aggregate data model powerful survive scrutiny; nor do estimable parametric versions of the individual data model. There is room for new stochastic identifying restrictions in empirical decision research.
The impact of thermal annealing temperature on the low-frequency noise characteristics of P3HT:PCBM bulk heterojunction organic solar cells

Abstract We investigate the dark low-frequency noise characteristics of P3HT:PCBM bulk heterojunction organic solar cells in both forward and reverse bias conditions. The current noise power spectral density (SI) is “1/f”-like and is compared among cells annealed at different temperatures (60 °C to 140 °C). The asymmetric relationship of SI versus DC dark current (IDC) can be explained by the competition between the recombination current noise and tunneling current noise. Among the different annealing temperatures, we find that higher annealing temperature yields smaller ratio of the Hooge parameter to the carrier recombination lifetime, which is reflected in the forward bias SI versus IDC relationship. We demonstrate that the low-frequency noise can serve as a non-destructive diagnostic indicator of the performance of organic solar cells.
NUMERICAL STUDY OF LIQUID COMPOSITE MOLDING USING A SMOOTHED PARTICLE HYDRODYNAMICS METHOD

Liquid composite molding is an important manufacturing process for a variety of composite components. The motion of fluid in a porous preform during a mold-filling process plays an important role in determining the quality of the composite part. In this study, a smoothed particle hydrodynamics (SPH) model is developed based on the BrinkmanForchheimer-Darcy equation to study the mold-filling process with a special emphasis on the effects of operational conditions on the distributions of the fluid in the preform. The capillary pressure, which is important for a metal-based composite, is included in the model using the continuum surface force method. Two-dimensional simulations were performed to examine the effects of infusion rate, multiple infusion gates, and capillary pressure on the filling process. The results suggest that the SPH model provides an effective tool with sufficient accuracy for simulation, design, and optimization of mold filling for complex components.
Benchmark calculations with correlated molecular wave functions. IV. The classical barrier height of the H+H2→H2+H reaction

Using systematic sequences of correlation consistent Gaussian basis sets from double to sextuple zeta quality, the classical barrier height of the H+H2 exchange reaction has been calculated by multireference configuration interaction (MRCI) methods. The MRCI calculations for collinear H3 have also been calibrated against large basis set full CI (FCI) results, which demonstrate that the MRCI treatment leads to energies less than 1 μhartree (≤0.001 kcal/mol) above the FCI energies. The dependence of both the H2 and H3 total energies on the basis set is found to be very regular, and this behavior has been used to extrapolate to the complete basis set (CBS) limits. The resulting estimate of the H–H–H CBS limit yields a classical barrier height, relative to exact H+H2, of 9.60±0.02 kcal/mol; the best directly calculated value for the barrier is equal to 9.62 kcal/mol. These results are in excellent agreement with recent quantum Monte Carlo calculations.
What is the Role of Antimicrobial Stewardship in Improving Outcomes of Patients with CAP

Community-acquired pneumonia (CAP) is one of the most common infectious diagnoses encountered in clinical practice and one of the leading causes of death in the United States. Adherence to antibiotic treatment guidelines is inconsistent and the erroneous diagnosis of CAP and misuse of antibiotics is prevalent in both inpatients and outpatients. This review summarizes interventions that may be promoted by antimicrobial stewardship programs to improve outcomes for patients with CAP.
ROSAT PSPC Observations of Cool Rich Clusters

We present the results of ROSAT PSPC observations of three cool (kT ≤ 3 keV) Abell clusters of galaxies (A262, A539, and A2589). Spatially resolved X-ray spectroscopy shows that the gas in these clusters is essentially isothermal beyond the central cooling flow region. The PSPC spectra of A262 also show excess soft X-ray absorption above that expected from the galactic hydrogen column density. The excess absorption is not confined to the central cooling flow region but is distributed across the entire field of view with a slight increase in absorption at large radii. We show that this excess absorption coincides with a region of galactic cirrus observed by IRAS. Using the 100 μm flux density toward A262, we derive a column density of molecular gas that is comparable to the column density of atomic gas and can account for the excess absorption. The spatial distribution of the molecular gas is also consistent with the observed variation in soft X-ray absorption across the PSPC field of view. Using the observed density and temperature profiles of the hot gas in these clusters, we determine their gravitating masses from the equation of hydrostatic equilibrium. The anisotropy parameter of the member galaxies is then calculated from the observed line-of-sight velocity dispersion and the X-ray—determined mass. For A262, we find that the early-type galaxies are virialized with a nearly isotropic velocity dispersion, while most of the spiral galaxies cannot be virialized for any value of the anisotropy parameter. There is also a strong alignment between the optical isophotes of the central dominant galaxy, the cluster X-ray isophotes in both A262 and A2589, and the large-scale orientation of the host supercluster. These results are consistent with a formation scenario in which clusters form through the accretion of gas and galaxies along large-scale filaments. We also calculate the entropy profile of the hot gas for a sample of groups, cool clusters, and hot clusters. We find that the gas entropy in cool clusters increases very gradually with radius while rich clusters show a much steeper gradient. The entropy of the core gas (beyond the cooling flow region) is essentially a constant in groups and rich clusters. These results suggest that the diffuse gas in groups and clusters was preheated before, or during, gravitational collapse. The marginal radial increase in the gas entropy in groups indicates that gravitational heating was almost negligible and the gas passed through weak shocks only as it was accreted. The steeper entropy gradient in rich clusters is consistent with the stronger shock heating expected in more massive systems.
Inhibitors of collagenase in ligaments and tendons of rabbits immobilized for 4 weeks.

Our laboratories have previously measured the capacity for collagenase production by normal and immobilized rabbit periarticular connective tissues (PCT), i.e., anterior cruciate ligaments (ACL), medial collateral ligament (MCL) and patellar tendon (PT). Rabbit limbs were immobilized for 4 weeks and then the tissues were cultured for 4 days. Collagenase and inhibitor (TIMP) were measured in the medium. Collagenase activity was significantly decreased in the medium from all experimental tissues, relative to the levels in contralateral control tissues. On the other hand there was no significant change in inhibitor levels in the three experimental tissues. These results support the idea that collagenase is decreased due to decreased enzyme expression and not to increased inhibitor production.
A rationale for the topological approach to chemistry

Abstract Chemists experience considerable difficulty in accepting many of the more exotic ideas of quantum mechanics such as the abolition of particulate matter and its replacement by the wave function. Even though the application of quantum theory in chemistry has been spectacularly successful in many areas, the underlying principles are counterintuitive and at best only vaguely comprehensible. Here we trace the development of our conception of the molecule over the past two centuries. It is shown that our notions have undergone a series of radical changes, starting from the rigid, solid-atom structure of Dalton, through the more flexible structure of Lewis held together by electron-pair bonds, to the modern conception of molecules defined solely in terms of ethereal wave functions. A major adjustment in the thinking of chemists has been necessary within a comparatively short space of time and so it is not surprising that this has left some feeling recalcitrant. A way forward is suggested that all concerned may find acceptable. This is to view the molecule not as a geometric entity but rather as a topological one. Several of the many advantages of adopting this stance are outlined toward the end of our article.
Blood Pressure Measurement in Shock: Mechanism of Inaccuracy in Auscultatory and Palpatory Methods

Arterial pressure was considerably higher than the cuff pressure obtained by auscultation or palpation of the brachial artery in 18 patients with shock and high total peripheral vascular resistance. Pulse pressure was also greatly underestimated by indirect measurement. This discrepancy was not observed in 21 hypotensive patients with low or normal resistance. Infusion of vasoconstrictor drugs into the arm circulation of normal subjects reproduced the clinical situation of normal arterial pressure with absent Korotkoff sounds and diminished radial pulses. High vascular resistance in the upper extremity prevents the hemodynamic events which normally produce the Korotkoff sounds. Disappearance of peripheral pulses is probably the result of reduced stroke volume and increased arterial wall stiffness.
Targeted Disruption of TGF-β/Smad3 Signaling Modulates Skin Fibrosis in a Mouse Model of Scleroderma

Transforming growth factor-β (TGF-β) is a potent stimulus of connective tissue accumulation, and is implicated in the pathogenesis of scleroderma and other fibrotic disorders. Smad3 functions as a key intracellular signal transducer for profibrotic TGF-β responses in normal skin fibroblasts. The potential role of Smad3 in the pathogenesis of scleroderma was investigated in Smad3-null (Smad3−/−) mice using a model of skin fibrosis induced by subcutaneous injections of bleomycin. At early time points, bleomycin-induced macrophage infiltration in the dermis and local TGF-β production were similar in Smad3−/− and wild-type mice. In contrast, at day 28, lesional skin from Smad3−/− mice showed attenuated fibrosis, lower synthesis and accumulation of collagen, and reduced collagen gene transcription in situ, compared to wild-type mice. Connective tissue growth factor and α-smooth muscle actin expression in lesional skin were also significantly attenuated. Electron microscopy revealed an absence of small diameter collagen fibrils in the dermis from bleomycin-treated Smad3−/− mice. Compared to fibroblasts derived from wild-type mice, Smad3−/− fibroblasts showed reduced in vitro proliferative and profibrotic responses elicited by TGF-β. Together, these results indicate that ablation of Smad3 is associated with markedly altered fibroblast regulation in vivo and in vitro, and confers partial protection from bleomycin-induced scleroderma in mice. Reduced fibrosis is due to deregulated fibroblast function, as the inflammatory response induced by bleomycin was similar in wild-type and Smad3−/− mice.