cssi/SciSciGPT-SciSciNet huggingface dataset:
Netrin-1 Alters Adipose Tissue Macrophage Fate and Function in Obesity.

Macrophages accumulate prominently in the visceral adipose tissue (VAT) of obese humans and high fat diet (HFD) fed mice, and this is linked to insulin resistance and type II diabetes. While the mechanisms regulating macrophage recruitment in obesity have been delineated, the signals directing macrophage persistence in VAT are poorly understood. We previously showed that the neuroimmune guidance cue netrin-1 is expressed in the VAT of obese mice and humans, where it promotes macrophage accumulation. To better understand the source of netrin-1 and its effects on adipose tissue macrophage (ATM) fate and function in obesity, we generated mice with myeloid-specific deletion of netrin-1 (Ntn1fl/fl LysMCre+/–; Ntn1mac). Interestingly, Ntn1mac mice showed a modest decrease in HFD-induced adiposity and adipocyte size, in the absence of changes in food intake or leptin, that was accompanied by an increase in markers of adipocyte beiging (Prdm16, UCP-1). Using single cell RNA-seq, combined with conventional histological and flow cytometry techniques, we show that myeloid-specific deletion of netrin-1 caused a 50% attrition of ATMs in HFD-fed mice, particularly of the resident macrophage subset, and altered the phenotype of residual ATMs to enhance lipid handling. Pseudotime analysis of single cell transcriptomes showed that in the absence of netrin-1, macrophages in the obese VAT underwent a phenotypic switch with the majority of ATMs activating a program of genes specialized in lipid handling, including fatty acid uptake and intracellular transport, lipid droplet formation and lipolysis, and regulation of lipid localization. Furthermore, Ntn1mac macrophages had reduced expression of genes involved in arachidonic acid metabolism, and targeted LCMS/MS metabololipidomics analysis revealed decreases in proinflammatory eicosanoids (5-HETE, 6-trans LTB4, TXB2, PGD2) in the obese VAT. Collectively, our data show that targeted deletion of netrin-1 in macrophages reprograms the ATM phenotype in obesity, leading to reduced adipose inflammation, and improved lipid handling and metabolic function.
Is Isolation Room Time-Out a Punisher?:

The commonly held assumption that time-out intervention, as represented by use of an isolation room, constitutes a punisher is disputed on empirical and theoretical ground. Consistent, unemotional ...
Cholera toxin promotes pathogen acquisition of host-derived nutrients.

Vibrio cholerae is the causative agent of cholera, a potentially lethal enteric bacterial infection1. Cholera toxin (CTX), a protein complex that is secreted by V. cholerae, is required for V. cholerae to cause severe disease. CTX is also thought to promote transmission of the organism, as infected individuals shed many litres of diarrhoeal fluid that typically contains in excess of 1011 organisms per litre. How the pathogen is able to reach such high concentrations in the intestine during infection remains poorly understood. Here we show that CTX increases pathogen growth and induces a distinct V. cholerae transcriptomic signature that is indicative of an iron-depleted gut niche. During infection, bacterial pathogens need to acquire iron, which is an essential nutrient for growth2. Most iron in the mammalian host is found in a chelated form within the porphyrin structure of haem, and the ability to use haem as a source of iron is genetically encoded by V. cholerae3. We show that the genes that enable V. cholerae to obtain iron via haem and vibriobactin confer a growth advantage to the pathogen only when CTX is produced. Furthermore, we found that CTX-induced congestion of capillaries in the terminal ileum correlated with an increased bioavailability of luminal haem. CTX-induced disease in the ileum also led to increased concentrations of long-chain fatty acids and l-lactate metabolites in the lumen, as well as the upregulation of V. cholerae genes that encode enzymes of the tricarboxylic acid (TCA) cycle that contain iron–sulfur clusters. Genetic analysis of V. cholerae suggested that pathogen growth was dependent on the uptake of haem and long-chain fatty acids during infection, but only in a strain capable of producing CTX in vivo. We conclude that CTX-induced disease creates an iron-depleted metabolic niche in the gut, which selectively promotes the growth of V. cholerae through the acquisition of host-derived haem and fatty acids. Cholera toxin selectively promotes the growth of Vibrio cholerae through the acquisition of nutrients, including haem and fatty acids, from the host gut.
"They are interrelated, one feeds off the other": A taxonomy of perceived disease interactions derived from patients with multiple chronic conditions.

Abstract Objective To understand patients’ experiences with condition interactions and develop a taxonomy to inform care for patients with multiple chronic conditions. Methods We conducted qualitative and quantitative analysis of free-text data from patient surveys in which respondents were asked to indicate their most bothersome chronic condition and describe how their other conditions affect their self-care for that condition. Using standard content analysis, we developed a taxonomy comprising how patients perceive interactions among their conditions, and examined cross-cutting themes that reflect qualities of these interactions. Results Among 383 eligible survey respondents, the mean (SD) number of chronic conditions was 4 (2); common conditions included hypertension (60%), chronic pain (49%), arthritis (41%), depression (32%), diabetes (29%), and post-traumatic stress disorder (26%). Patients’ perceived condition interactions took four broad forms: 1) unidirectional interactions among conditions and/or treatments, 2) cyclical or multidimensional interactions, 3) uncertain or indistinct interactions, and 4) no perceived interaction. Cross-cutting themes included beliefs about causal relationships between conditions, identification of interactions as negative vs. positive, and interactions between physical and mental health. Conclusion This study presents a novel taxonomy of condition interactions from the patient perspective. Practice Implications Understanding perceived condition interactions may support patient self-management and shared decision-making efforts.
Optimizing Quality of Life With Cognitive Impairment: A Study of End-of-Life Care in Assisted Living.

Abstract Objectives Assisted living (AL) is an expanding site of end-of-life (EOL) care in the United States. Understanding determinants of quality of life (QoL) for AL residents near EOL is vital to optimize care for this growing population, most of whom have some degree of cognitive impairment (CI). This analysis aimed to identify factors associated with QoL in a diverse sample of AL residents with CI approaching EOL. Design Observational cross-section design. Setting and participants Data are from a 5-year study funded by the National Institute on Aging examining EOL care of residents in 7 diverse AL communities in metropolitan Atlanta (n = 67). Methods CI was assessed with the Montreal Cognitive Assessment (scores ≤ 26) and QoL was determined with the self-reported QoL in Alzheimer's disease survey adapted for use in AL. Psychological distress was assessed using the Patient Health Questionnaire–4 and fatigue was assessed using the 13-item Functional Assessment of Chronic Illness Therapy Fatigue Scale. Initial descriptive analyses were followed by backward stepwise regression analyses to select a best-fitting model of QoL. Results The final model predicted 27% of the variance in QoL. CI was not significantly correlated with QoL and was not retained in the final model. Pain and functional limitation also did not meet inclusion criteria (P ≤ .10) and were sequentially removed, producing a final model of QoL in terms of psychological distress (β = −0.28, P = .032), fatigue (β = −0.26, P = .048), and race (β = 0.21, P = .063). Conclusions and Implications The lack of a significant correlation between degree of CI and self-reported QoL suggests that AL residents have the potential to experience high QoL, despite CI. Interventions to reduce psychological distress and manage fatigue could be implemented during EOL care to attempt to improve QoL for AL residents with CI. The correlation between race and QoL warrants investigation into possible racial disparities in AL and EOL care.
RNA Polymerase's Relationship with the Ribosome: Not So Physical, Most of the Time

In bacteria, the rates of transcription elongation and translation elongation are coordinated, changing together in response to growth conditions. It has been proposed that this is due to physical coupling of RNA polymerase and the lead ribosome on nascent mRNA, an interaction important for preventing premature transcription termination by Rho factor. Recent studies challenge this view and provide evidence that coordination is indirect, mediated in Escherichia coli by the alarmone (p)ppGpp. Here, we discuss these new findings and how they shape our understanding of the functional relationship between RNA polymerase and the ribosome as well as the basis of transcriptional polarity.
Chapter 40 – Triton

Triton is the major moon of Neptune. It was discovered shortly after Neptune's discovery and orbits in a retrograde, or backward, sense compared with Neptune's rotation. Composed of a rock and metal core and a massive icy mantle, and probably an internal ocean, Triton displays a variety of active geological processes including cryo-, or cold, volcanism; tectonic deformation; and active plume eruptions. The latter are thought to be driven by solar heating of a predominantly nitrogen ice surface. Along with methane and other exotic ices, this extremely cold nitrogen ice maintains a thin atmosphere in vapor pressure equilibrium. This tenuous atmosphere supports hazes and clouds and high winds and is subject to strong seasons. Triton is thought to be a captured body from the Kuiper belt beyond Neptune, and as such offers a glimpse of what major bodies in the Kuiper belt, such as Pluto and Eris, may be like.
Abstract PO-064: Inhibition of RAS signaling and tumorigenesis through novel targeting novel vulnerabilities

RAS GTPases are important mediators of oncogenesis with nearly 20% of human tumors harboring mutant RAS proteins. However, pharmacological inhibition of RAS has proven challenging. We have employed Monobody technology to discover novel vulnerabilities in RAS that can be exploited to inhibit RAS signaling and tumorigenesis. Monobodies are single-domain synthetic binding proteins that achieve levels of affinity and selectivity similar to antibodies. In contrast to antibodies, Monobodies are fully functional in the reducing environment of the cytoplasm and thus are particularly suitable as genetically encoded “tool biologics”. We previously developed the NS1 Monobody that inhibited RAS by targeting the α4-α5 allosteric lobe to prevent RAS self-association and nanoclustering, and NS1 has become a widely used tool in the RAS research community. Following on this success, we sought to identify additional vulnerabilities in RAS. Based on our discovery that nucleotide-free RAS (apoRAS) inhibits PIK3C2B function, we assessed the feasibility of selectively targeting this state of RAS as an approach to inhibit RAS. Here, we have developed several Monobodies and extensively characterized one of them, R15. Although NS1 was agnostic to the nucleotide state of RAS, R15 bound exclusively to the apo state of all three RAS isoforms but did not interact with nucleotide-loaded RAS. When expressed in cells, R15 inhibited the signaling and transforming activity of RAS mutants with elevated intrinsic nucleotide exchange rates (i.e., “fast exchange mutants”), such as G13D and Q61L, but was ineffective against slow exchange mutants such as G12V. Surprisingly, R15 also bound and inhibited RAS(G12D), the most common oncogenic KRAS mutation in pancreatic cancer. Biochemical studies demonstrated that R15 captured RAS from cell lysates in the nucleotide-free state, suggesting that R15 traps apoRAS and prevents nucleotide reloading. Disruption of SOS binding by mutation of D69N further enhanced R15 binding to these fast exchange RAS mutants. Finally, inducible expression of R15 selectively inhibited the tumor forming capacity of tumor lines and patient derived xenografts driven by fast exchange RAS mutants, including RAS(G12D), but not RAS(G12V). Thus, in contrast to conventional wisdom, our approach has established a new opportunity to selectively inhibit the tumorigenic activity of certain RAS mutants by targeting the apo state of RAS with drug-like molecules. Citation Format: Imran Khan, Akiko Koide, Mariyam Zuberi, Eric Denbaum, Gayatari Ketavar, Kai-Wen Teng, Matthew Rhett, Russell Sepncer-Smith, Ernest R. Camp, Shohei Koide, John O’Bryan. Inhibition of RAS signaling and tumorigenesis through novel targeting novel vulnerabilities [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-064.
Knockdown of Alpha-1 Antitrypsin with antisense oligonucleotide does not exacerbate smoke induced lung injury

Alpha-1 Antitrypsin (AAT) is a serum protease inhibitor that regulates increased lung protease production induced by cigarette smoking. Mutations in the Serpina1 gene cause AAT to form hepatoxic polymers, which can lead to reduced availability for the protein's primary function and severe liver disease. An AAT antisense oligonucleotide (ASO) was previously identified to be beneficial for the AATD liver disease by blocking the mutated AAT transcripts. Here we hypothesized that knockdown of AAT aggravates murine lung injury during smoke exposure and acute exacerbations of chronic obstructive pulmonary disease (COPD). C57BL/6J mice were randomly divided into 4 groups each for the smoking and smoke-flu injury models. The ASO and control (No-ASO) were injected subcutaneously starting with smoking or four days prior to influenza infection and then injected weekly at 50 mg/kg body weight. ASO treatment during a 3-month smoke exposure significantly decreased the serum and lung AAT expression, resulting in increased Cela1 expression and elastase activity. However, despite the decrease in AAT, neither the inflammatory cell counts in the bronchoalveolar lavage fluid (BALF) nor the lung structural changes were significantly worsened by ASO treatment. We observed significant differences in inflammation and emphysema due to smoke exposure, but did not observe an ASO treatment effect. Similarly, with the smoke-flu model, differences were only observed between smoke-flu and room air controls, but not as a result of ASO treatment. Off-target effects or compensatory mechanisms may account for this finding. Alternatively, the reduction of AAT with ASO treatment, while sufficient to protect from liver injury, may not be robust enough to lead to lung injury. The results also suggest that previously described AAT ASO treatment for AAT mutation related liver disease may attenuate hepatic injury without being detrimental to the lungs. These potential mechanisms need to be further investigated in order to fully understand the impact of AAT inhibition on protease-antiprotease imbalance in the murine smoke exposure model.
Deciding how to make climate change adaptation decisions

Deciding how and when to adapt to climate change is a difficult problem, involving multiple actors and problem frames, deep uncertainty, and contested goals. Numerous decision-making strategies have been developed to reduce uncertainty, evaluate options under multiple future scenarios, or create decision pathways in an effort to overcome barriers that prevent adaptation decision-making from being a ‘rational’ process: a careful and objective evaluation of how alternative options perform under future conditions. Other fields, such as cognitive science, economics, and psychology, have explored alternatives to rational decision-making such as heuristics, and applied adaptation research has illustrated the role of context in shaping decision-making. This article reviews recent research on adaptation decision-making strategies and highlights gaps that future research should address to inform practice. While decision-making methods and tools have proliferated, there is still a lack of research on how adaptation strategies are selected in practice and a need for research on the meta-decision-making question: How should decision-makers choose which decision-making process to use?
Concepts, Methods, and Tools Enabling Measurement Quality

This contribution provides an overview, illustrated with examples, of applications of statistical methods that support measurement quality and guarantee the intercomparability of measurements made worldwide, in all fields of commerce, industry, science, and technology, including medicine. These methods enable a rigorous definition of measurement uncertainty, and provide the means to evaluate it quantitatively, both for qualitative measurands (for example, the sequence of nucleobases in a DNA strand) and for quantitative measurands (for example, the mass fraction of arsenic in rice). Measurement quality is its trustworthiness and comprises several attributes: reliable calibration involving standards; traceability to the international system of units or to other generally recognized standards; measurement uncertainty that realistically captures contributions from all significant sources of uncertainty; and fitness for purpose of the measurement results, which comprise measured values and evaluations of associated uncertainties. Statistical methods play key roles in the quality system that validates the measurement services (reference materials, calibrations, reference data, and reference instruments) provided by the National Institute of Standards and Technology (NIST). And these services in turn support measurement quality in laboratories, factories, farms, hospitals, transportation, utilities, and weather and environmental monitoring stations throughout the world, contributing to ensure food safety, to manufacture reliable products, and to monitor industrial and natural processes accurately. The NIST Uncertainty Machine (NUM) and the NIST Consensus Builder (NICOB) are web-based tools freely available to metrologists everywhere, that help maintain measurement quality. The NUM serves to evaluate measurement uncertainty and the NICOB builds consensus values from measurement results obtained independently for the same measurand.
Towards event-driven decentralized marketplaces on the blockchain

Blockchains have become a popular technology for lowering the trust-tax burden between transacting parties that cannot necessarily trust each other. They are used as substitutes for the centralized authorities typically incorporated in transactional workflows to perform verification tasks and have the advantage of being objective and incorruptible. For applications such as supply chain marketplaces, auxilliary functionalities beyond the core blockchain roles of recording and validating transactions such as event detection are important for enabling application participants be responsive to business conditions. Unfortunately, existing blockchain event frameworks are immature, syntactic, inflexible and not expressive enough for many application needs. In this paper, we propose an approach that involves an event model which "semantifies blockchain transactions" and an implementation architecture that integrates a open-source blockchain database BigChainDB with a semantic engine and publish-subscribe messaging platform. Finally, we model and simulate a use-case inspired from the manufacturing domain and present usability and preliminary performance results that demonstrate the discriminatory ability of semantics-enabled event model.
Quantitative Phase Velocimetry for Label-Free Measurement of Intracellular Mass Transport Velocity

ABSTRACT Transport of mass within cells helps maintain homeostasis and is disrupted by disease and stress. Here, we develop quantitative phase velocimetry (QPV) as a label-free approach to make the invisible flow of mass within cells visible and quantifiable. We benchmark our approach against alternative image registration methods, a theoretical error model, and synthetic data. Our method tracks not just individual labeled particles or molecules, but the entire flow of material through the cell. This enables us to measure diffusivity within distinct cell compartments using a single approach, which we use here for direct comparison of nuclear and cytoplasmic diffusivity. As a label-free method, QPV can be used for long-term tracking to capture dynamics through the cell cycle. Finally, based on the known effective particle size, we show that QPV is an accessible method to measure intracellular viscosity.
Deep learning–assisted prostate cancer detection on bi-parametric MRI: minimum training data size requirements and effect of prior knowledge

To assess Prostate Imaging Reporting and Data System (PI-RADS)–trained deep learning (DL) algorithm performance and to investigate the effect of data size and prior knowledge on the detection of clinically significant prostate cancer (csPCa) in biopsy-naive men with a suspicion of PCa. Multi-institution data included 2734 consecutive biopsy-naive men with elevated PSA levels (≥ 3 ng/mL) that underwent multi-parametric MRI (mpMRI). mpMRI exams were prospectively reported using PI-RADS v2 by expert radiologists. A DL framework was designed and trained on center 1 data (n = 1952) to predict PI-RADS ≥ 4 (n = 1092) lesions from bi-parametric MRI (bpMRI). Experiments included varying the number of cases and the use of automatic zonal segmentation as a DL prior. Independent center 2 cases (n = 296) that included pathology outcome (systematic and MRI targeted biopsy) were used to compute performance for radiologists and DL. The performance of detecting PI-RADS 4–5 and Gleason > 6 lesions was assessed on 782 unseen cases (486 center 1, 296 center 2) using free-response ROC (FROC) and ROC analysis. The DL sensitivity for detecting PI-RADS ≥ 4 lesions was 87% (193/223, 95% CI: 82–91) at an average of 1 false positive (FP) per patient, and an AUC of 0.88 (95% CI: 0.84–0.91). The DL sensitivity for the detection of Gleason > 6 lesions was 85% (79/93, 95% CI: 77–83) @ 1 FP compared to 91% (85/93, 95% CI: 84–96) @ 0.3 FP for a consensus panel of expert radiologists. Data size and prior zonal knowledge significantly affected performance (4%, $$p<0.05$$ ). PI-RADS-trained DL can accurately detect and localize Gleason > 6 lesions. DL could reach expert performance using substantially more than 2000 training cases, and DL zonal segmentation. • AI for prostate MRI analysis depends strongly on data size and prior zonal knowledge. • AI needs substantially more than 2000 training cases to achieve expert performance.
Tandem distributed detection with conditionally dependent observations

This paper deals with distributed detection using a tandem network with conditionally dependent observations. Our approach utilizes a recently proposed hierarchical conditional independence model where a hidden variable is introduced and induces conditional independence among sensor observations. If the hidden variable is discrete, optimal local decision rules are reminiscent that of the conditional independence case. For continuous scalar hidden variable, similar results can be obtained when additional monotonicity conditions are imposed.
The development and evaluation of a model of Responsible Leadership for Performance

The model for ‘Responsible Leadership for Performance’ represents a unique perspective on sustainable leadership. The core contribution of this effort is the integration of the ‘personal characteristics’ view of leaders at the top and the ‘performance/systems’ view of the complexity of the organization, along with the recognition that leadership requires willing followership.
N-(3-Pyrene)maleimide: a Long Lifetime Fluorescent Sulfhydryl Reagent

We report the chemical synthesis and some useful applications of N-(3-pyrene)maleimide which forms fluorescent adducts with organic compounds and proteins which contain sulfhydryl groups. Lifetime of the first excited singlet state of the small molecule adducts ranged from 1.4 to 6.5 ns. Fluorescence of the protein adducts exhibited two distinct lifetimes for each adduct. The longer component had a value of about 100 ns. Because of the long lifetime, N-(3-pyrene)maleimide is useful for fluorescence polarization studies of high molecular weight proteins and other macro-molecules having reactive sulfhydryl groups.
Practitioner review: Psychopharmacology in children and adolescents with mental retardation.

Background: The use of psychotropic medication to treat children and adults with mental retardation (MR) has a long and extensive history. There are no identified medications to address specific cognitive deficits among persons with MR. Instead, psychotropic medications are used to treat specific behavioral symptoms and/or psychiatric syndromes. The purpose of this review is to provide an overview of the recent literature regarding the use of psychotropic medications in this population, focusing primarily on children and adolescents. Methods: The paper is divided into five general drug categories: psychostimulants, antipsychotics, antidepressants, mood stabilizers, and other drugs. Each section offers an overview of the research supporting the use of that class of medications in children and adolescents with MR as well as cautions regarding potential side effects. Finally, specific clinical recommendations are offered. Results: The majority of studies in MR tend to be open trials, case reports, or controlled studies with small samples. The available data suggests that persons with MR respond to various psychotropic medications in ways similar to the typically developing population. However, rates of response tend to be poorer and the occurrence of side effects tends to be more frequent. Conclusions: The use of psychotropic medications in children and adolescents with MR requires even greater monitoring and the use of lower doses and slower dosage increases than in the general population.
Chapter 10 Retention and selectivity for polycyclic aromatic hydrocarbons in reversed-phase liquid chromatography

Publisher Summary This chapter describes retention and selectivity for polycyclic aromatic hydrocarbons (PAHs) in reversed-phase liquid chromatography (LC). PAHs are widespread environmental contaminants resulting from emissions from a variety of sources including: industrial combustion, discharge of fossil fuels, residential heating, and motor vehicle exhausts. PAHs are usually present in environmental samples as extremely complex mixtures which contain numerous alkylated and non-alkylated isomers that vary greatly in relative concentration and carcinogenic or mutagenic properties. Because of excellent separation and detection selectivity of reversed-phase LC, this technique has been specified as the method of choice by the US Environmental Protection Agency (EPA) for the determination of PAHs in aqueous effluent. The ability of a column to discriminate among PAH isomers (and other classes of compounds) on the basis of the molecular structure is described as “shape selectivity.” The single most important parameter affecting column shape selectivity towards PAHs is a property involving phase structure—namely, the phase type. Differences in column selectivity between monomeric and polymeric C 18 phases are readily apparent for separations of PAH isomers.
2.07-micron CW diode-laser-pumped Tm,Ho:YLiF4 room-temperature

Continuous-wave action is obtained at 2.07 microns from a 2-mm-long Tm-sensitized Ho:YLiF4 crystal at room temperature when longitudinally pumped by a pair of diode-laser arrays. Laser output power at 300 K is 26 mW, with a 30-percent slope efficiency and a lasing threshold of 108 mW. A maximum output power of 187 mW is obtained from a 4-mm-long crystal at 77 K, with a 67 percent slope efficiency. A preliminary demonstration of cavity Q switching produced 165 microJ of pulse energy at a repetition rate of 100 Hz.
Generalized spectral decomposition, with application to the reduced transport operator

The spectral decomposition of certain unbounded operators can, in some cases, be simplified by a method called «generalized spectral decomposition». The generalized spectrum is not necessarily equal to the spectrum, but several useful containment theorems are proved. This technique is applied to the spectral decomposition of the reduced transport operator in one space dimension. In particular, under the assumption that the scattering kernel is degenerate and each element square integrable, it is shown that the generalized spectral decomposition is identical with the ordinary spectral decomposition.
Analysis of racemization during "Standard" solid phase peptide synthesis: a multicenter study

Publisher Summary Evaluation of the degree to which racemization occurs in peptides produced by core laboratories is very appropriate. The Peptide Synthesis Research Committee of the Association of Biomolecular Resource Facilities (ABRF) conducts anonymous studies to evaluate the ability of ABRF member laboratories to synthesize and characterize test peptides. The committee prepared for the 1996 study by designing and testing appropriate short peptides that should be straightforward to synthesize. 48 laboratories participated in this study, submitting 53 samples for analysis. In addition to the results of this multicenter study, this chapter also discusses a summary of the committee's preparatory experiments. During the preparatory phase of this study, it was found that handling and analysis of a hexapeptide with two potential sites of racemization were too problematic to be useful as a model for this multicenter study. A hexapeptide susceptible to racemization at a single His residue was subsequently designed, tested, and found suitable for the study. This synthetic peptide was requested from each of the core laboratories for evaluation by the committee. Coded samples of unpurified peptides were characterized by amino acid analysis (AAA), AAA following reaction with Marfey's reagent, high pressure liquid chromatography (HPLC), electrospray ionization mass spectrometry (ESI-MS), matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS), and enzymatic digestion by carboxypeptidase A (CPA) followed by MALDI-MS. The overall results from this study indicate that racemization during peptide assembly is not a serious problem in most participating laboratories. Nevertheless, it is evident that laboratories can produce peptides that have predominantly composed of the desired product, yet exhibit unacceptably high levels of racemization.
Nonlinear Mixed Effects Models: Theory

This chapter introduces the theory behind nonlinear mixed effects models through the concept of a structural model or covariate model coupled to both fixed and random effects in a nonlinear manner. Modeling and estimation of model parameters in the face of different sources of variability (between-subject, inter-occasion, inter-study, and residual or within-subject) are discussed, as is modeling the nature of the relationship between the covariate and dependent variable via linear, power, and exponential functions. Model building, identifying significant covariates through covariate screening and covariate modeling, influence analysis, and examination of goodness of fit through both scrutiny of the model building data set and validation via internal and external techniques are discussed.
A Weighted Ensemble Kalman Filter for Automatic History Matching

Abstract The ensemble Kalman filter (EnKF) performs the initial sampling, forecasting, and assimilation steps for automatic history matching in the petroleum industry. It tunes multiple members sequentially and updates the statistical mean and variance of the model. Many applications have been reported in various publications. The forecasting step is implemented by running the reservoir model simulator. In the assimilation equation, the ensemble mean is calculated through equally weighting all the members. Therefore, the contribution factor to the mean from each member is the same. This paper proposes a modified assimilation equation by introducing a weighting factor for each ensemble member. Both the proposed weighted EnKF and the traditional EnKF are applied to a modified field case of a complex seventeen-layer reservoir. The performances of the weighted EnKF on production history match, forecasting, and field permeability match are better than those from the traditional EnKF. In addition, we investigat...
"HOW HAPPY WAS I, ANYWAY?" A RETROSPECTIVE IMPACT BIAS

Abstract People often overestimate the impact future events will have on their happiness. People may also show a retrospective impact bias, overestimating the impact of past events on their happiness, explaining why they do not learn from experience and correct their forecasts. We found such a bias for positive events; e.g., supporters of George Bush overestimated how happy they had been when the U. S. presidential election was determined. For negative events, people's recall was related to how much they were still rationalizing the outcome. Gore supporters rationalized the election by changing their views of the candidates. Four months later their positive view of Gore had returned, and they overestimated how unhappy they had been. In Study 2, poor performers on a test rationalized their performance by downplaying the test's validity. Two weeks later they continued to rationalize, and recalled accurately that they had not been very upset by their performance.
Inverse problems in neuronal calcium signaling

Calcium is the most important of the brain’s second messengers. Thanks to engineered fluorescent indicators and caged compounds we have an excellent qualitative picture of its regulation and impact. With the advent of new scanning technology that permits one to observe the calcium signal throughout a highly branched neuron the potential exists for functional, single cell, quantitative calcium imaging. To help realize that potential we analyze a sequence of four inverse problems that infer the parameters of the cytosolic calcium buffers and plasma membrane calcium pumps and channels from the light shed by fluorescent indicators following specific stimulus protocols. Our analyses lead in each case to practical algorithms that we illustrate and test on synthetic data.
Development of symbiotic bacterial bioluminescence in a nearshore cephalopod, Euprymna scolopes

The small neritic cephalopod Euprymna scolopes possesses a large glandular light organ that contains the symbiotic luminous bacterium Vibrio fischeri. Adult and immature E. scolopes were caught in the evening with dip nets in shallow water along the shore of Kanohe Bay, Oahu, Hawaii, during late February 1984. The initiation of the symbiosis was investigated by rearing the cephalopods either in seawater taken from aquaria containing adult E. scolopes or in seawater with reduced bacterial concentrations due to filtration or due to absence of adults. Light production was measured during early development. Bioluminescence was not detected in E. scolopes immediately after hatching. Most individulas of E. scolopes that hatched into seawater containing, or previously exposed to, adults produced light within 24 h. Individuals that hatched into filtered seawater did not produce light. The data suggest that each generation aquires an infection from free-living bacteria rather than from the egg, and that light production is dependent on the nutritional state of the host. Access to an initial inoculum of free-living, luminous bacteria seems to be critical for establishing a successful symbiosis.
Why we lose interest in sex : Do neurosteroids play a role?

For couples desiring but having difficulty experiencing intercourse, great strides have been achieved to treat physical obstacles (such as erectile dysfunction); but a little blue pill to treat a loss of sexual desire does not yet exist. Neurosteroids, the steroids produced within the brain, may offer hope.
Fidia Longipes as a Grape Pest

The grape root worm ( Fidia viticida Walsh) is replaced in importance in the grape belt of Arkansas by F. longipes Melsh.2 A summary of the habits and life history of the latter species is given.
Ideal Homes and the Gender Politics of Consumerism in Postcolonial Ghana, 1960–70

This article uses the 1967 Ideal Home Exhibition in Accra as a window onto understanding connections between gender and consumerism in postcolonial Ghana. Drawing upon newspapers, comics and novels, it argues that the home was placed at the centre of national debates about economic recovery and political stability. Major goals of attracting Western investors and building Ghana's private sector simultaneously promoted conservative gender roles and restrictions on consumer behaviour. Cultural stereotypes targeting the consumption habits of women and youth intensified in the postcolonial period, masking larger issues like unstable wages, increasing foreign debts, high costs of living and government corruption.
Prognostic Factors for Survival With Gemcitabine Plus 5-fluorouracil Based Regimens for Metastatic Renal Cancer

ABSTRACTPurpose: Combination gemcitabine and 5-fluorouracil (5-FU) may have activity in metastatic renal cell cancer. To identify patient subgroups most likely to benefit and compare survival to that in previously described patient series long-term survival as a function of known and suspected prognostic variables was determined.Materials and Methods: The survival status of 153 patients with metastatic renal cell cancer treated on 1 phase I and 4 phase II trials of gemcitabine/5-FU based regimens was updated. Univariate and multivariate Cox proportional hazards models were constructed using multiple imputation for missing values.Results: Performance status, prior nephrectomy, number of metastatic sites, decreased albumin and elevated alkaline phosphatase were highly prognostic for survival. Sarcomatoid differentiation and hypercalcemia had borderline prognostic significance. Using a previous described prognostic model that divided patients into 3 risk groups survival in those treated with gemcitabine/5-FU...
Shifts in macrophage (Mφ) surface phenotypes during tumor growth: Association of Mac-2+ and Mac-3+ Mφ with immunosuppressive activity☆

Abstract Rat anti-mouse monoclonal antibodies (mAb), anti-Mac-1, -2, and -3, directed against macrophage (Mφ) glycoprotein surface antigens, were used to demonstrate a tumor-induced shift in peritoneal Mφ subpopulations. This study of the tumor-induced shift was approached in two steps. First, to show that separate phenotypic Mφ subpopulations existed and second, to show that a shift in these populations was involved in immunosuppression of the host during tumor growth. Endogenous peroxidase activity was examined among normal and tumor-bearing host (TBH) Mφ. A significant increase in the number of peroxidase-positive Mφ occurred during tumor growth. Indirect immunofluorescence showed a decrease in Mac-2+ cells and an increase in Mac-3+ cells in TBH Mφ populations. When the mAb, anti-Mac-1, -2, and -3 were used in the presence of complement (C), they were cytotoxic for Mφ and showed differential depletion of normal and TBH Mφ. Peroxidase-positive TBH Mφ were susceptible to C-mediated lysis by anti-Mac-1 and -3 but not by anti-Mac-2, whereas no direct relationship was observed among normal host Mφ. To demonstrate differences between normal and TBH Mφ subpopulations, soluble inhibitory factors were examined from mAb plus C-modified Mφ populations. Anti-Mac plus C-treated normal and TBH Mφ produced supernatants with different regulatory capabilities as assessed in the mixed-lymphocyte reaction (MLR). Anti-Mac-2 plus C treatment significantly reduced the ability of TBH Mφ to produce a soluble suppressor(s) but did not alter normal host Mφ-derived suppressor production. In contrast, anti-Mac-1 and -3 plus C treatment of normal host Mφ significantly reduced suppressor production. In the TBH, however, anti-Mac-1 plus C had no effect, while anti-Mac-3 plus C had only a limited reduction as compared to the normal host. Determination of levels of prostaglandin E2 (PGE2) in Mφ supernatants showed that normal host Mac-1+ Mφ were involved in down regulation of PGE2 production. This control was missing in the TBH Mφ. Mac-2+ Mφ were the apparent producers of PGE2 which accounts for the factor-mediated MLR suppression attributed to TBH Mac-2+ Mφ. Collectively, these data suggest that tumor-induced aberrations in immunoregulation can in part be attributed to differences in anti-Mac mAb-defined Mφ subpopulations.
Evaluation of Natural and Engineered Resistance Mechanisms in Solanum tuberosum for Resistance to Phthorimaea operculella (Lepidoptera: Gelechiidae)

Potato tuber moth, Phthorimaea operculella Zeller, is a highly destructive pest of cultivated potato, Solanum tuberosum L., and is responsible for damage to both leaf and tuber tissues. Host plant resistance is a central component to developing an integrated pest management program to control potato tuber moth. This research tested the efficacy of a codon-modified CryV- Bacilius thuringiensis (CryV-Bt) gene constitutively expressed in potato and the combined effect of CryV-Bt expression with natural host plant resistance mechanisms in potato. ‘Lemhi Russet’ and 2 lines with host plant resistance mechanisms, USDA8380-1 (leaf leptines) and L235-4 (glandular trichomes), along with the CryV-Bt-transgenic lines of each of these 3 genotypes were examined. Detached leaf bioassays were conducted to examine control of potato tuber moth. Nontransformed Lemhi Russet and L235-4 were susceptible to potato tuber moth, while 54%potato tuber moth mortality was found when first instar larvae fed on USDA8380-1Ieaves. High levels of expression occurred in the CryV-Bt transgenic lines, with up to 96% potato tuber moth mortality. These transgenic lines provide a germplasm base to examine combined insect-resistance mechanisms as a means to achieve durable host plant resistance.
Three-dimensional shape construction and recognition by fusing intensity and structured lighting

Abstract In this paper, a new technique is developed for three-dimensional (3D) shape reconstruction and recognition from two-dimensional (2D) images of multiple objects with mutual occlusion. To facilitate such an analysis, both intensity and structured-light coded images are used. From intensity images, equi-brightness contours, which are swaths of points sharing similar intensities, are located. It is shown that equi-brightness contours possess distinct shape and orientation for different types of surfaces, and hence, can be used to distinguish them. To achieve a quantitative description of the shape and orientation of the imaged surfaces, the projected pattern in the corresponding structured-light coded images is analyzed. A scheme is developed which relates the orientation and curvature of the projected pattern observed in the structured-light images to the surface orientation and principal surface curvatures of the imaged objects.
Strength in numbers: non-natural polyvalent carbohydrate derivatives

Many processes mediated by protein-carbohydrate interactions involve multivalent low-affinity binding, which is inherently difficult to study. New structural templates for the generation of multivalent carbohydrate displays have recently been developed, and tailored multivalent saccharide derivatives can now be used to study and modulate a wide variety of biological recognition events.
Type of oral cleft and mothers' perceptions of care, health status, and outcomes for preadolescent children.

Abstract Objective: To evaluate the outcomes of care for children by type of oral cleft. Design: Data were collected through structured telephone interviews during 2003 in Iowa with mothers of 2- to 12-year-old children with oral clefts. Interviews with mothers of children with clubfoot and statewide data on Iowa children were used for comparison. Participants: Participants included mothers of children in Iowa born between 1990 and 2000 with nonsyndromic oral clefts. Children were identified by the statewide Iowa Registry for Congenital and Inherited Disorders. Main Outcome Measures: Rating of cleft care, severity of condition, health status, esthetic outcome, speech, and school performance were evaluated by type of oral cleft. Results: Children with cleft lip and palate were most likely to have their clefts rated as very severe. Children with palatal involvement were reported to have a lower health status and were almost twice as likely to be identified as having a special health care need compared with ...
An Assessment of Sampling Mortality of Larval Fishes

Abstract A study was initiated to assess the mortality of larval fishes that were entrained in the condenser cooling systems of two nuclear power plants on the Missouri River in Nebraska. High mortalities were observed not only in the discharge collections but also in control samples taken upriver from the plants where no entrainment effects were possible. As a result, entrainment mortality generally could not be demonstrated. A technique was developed which indicated that (1) a significant portion of the observed mortality above the power plants was the result of net-induced sampling mortality, and (2) a direct relationship existed between observed mortality and water velocity in the nets when sampling at the control sites, which was described by linear regression equations. When these equations were subsequently used to remove the effects of wide differences in sampling velocities between control and discharge collections, significant entrainment mortality was noted in all cases. The equations were also...
N-terminal sequence homologies in interstitial retinol-binding proteins from 10 vertebrate species

Abstract We report here the first comprehensive comparative NH 2 -terminal sequence studies of interstitial retinolbinding protein (IRBPs) from nine mammals (including cattle) and one amphibian. This study has revealed that in many species the N-terminus of IRBP includes a 3–6 amino acid extension. IRBP possessing this leader sequence is sometimes mixed with IRBP from which this sequence has been excised.
High-Strength Undiffused Brushless (HSUB) Machine

This paper introduces a new high-strength undiffused brushless machine that transfers the stationary excitation magnetomotive force to the rotor without any brushes. For a conventional permanent magnet (PM) machine, the air gap flux density cannot be enhanced effectively but can be weakened. In the new machine, both the stationary excitation coil and the PM in the rotor produce an enhanced air gap flux. The PM in the rotor prevents magnetic flux diffusion between the poles and guides the reluctance flux path. The pole flux density in the air gap can be much higher than what the PM alone can produce. A high-strength machine is thus obtained. The air gap flux density can be weakened through the stationary excitation winding. This type of machine is particularly suitable for electric and hybrid-electric vehicle applications. Patents of this new technology are either granted or pending.
The Effects of Exercise Training on Anxiety

This review summarizes the extant evidence of the effects of exercise training on anxiety among healthy adults, adults with a chronic illness, and individuals diagnosed with an anxiety disorder. A brief discussion of selected proposed mechanisms that may underlie relations of exercise and anxiety is also provided. The weight of the available empirical evidence indicates that exercise training reduces symptoms of anxiety among healthy adults, chronically ill patients, and patients with panic disorder. Preliminary data suggest that exercise training can serve as an alternative therapy for patients with social anxiety disorder, generalized anxiety disorder, and obsessive–compulsive disorder. Anxiety reductions appear to be comparable to empirically supported treatments for panic and generalized anxiety disorders. Large trials aimed at more precisely determining the magnitude and generalizability of exercise training effects appear to be warranted for panic and generalized anxiety disorders. Future well-desig...