cssi/SciSciGPT-SciSciNet huggingface dataset:
The pseudokinase domains of guanylyl cyclase–A and –B allosterically increase the affinity of their catalytic domains for substrate

Natriuretic peptides regulate multiple physiologic systems by activating transmembrane receptors containing intracellular guanylyl cyclase domains, such as GC-A and GC-B, also known as Npr1 and Npr2, respectively. Both enzymes contain an intracellular, phosphorylated pseudokinase domain (PKD) critical for activation of the C-terminal cGMP-synthesizing guanylyl cyclase domain. Because ATP allosterically activates GC-A and GC-B, we investigated how ATP binding to the PKD influenced guanylyl cyclase activity. Molecular modeling indicated that all the residues of the ATP-binding site of the prototypical kinase PKA, except the catalytic aspartate, are conserved in the PKDs of GC-A and GC-B. Kinase-inactivating alanine substitutions for the invariant lysine in subdomain II or the aspartate in the DYG-loop of GC-A and GC-B failed to decrease enzyme phosphate content, consistent with the PKDs lacking kinase activity. In contrast, both mutations reduced enzyme activation by blocking the ability of ATP to decrease the Michaelis constant without affecting peptide-dependent activation. The analogous lysine-to-alanine substitution in a glutamate-substituted phosphomimetic mutant form of GC-B also reduced enzyme activity, consistent with ATP stimulating guanylyl cyclase activity through an allosteric, phosphorylation-independent mechanism. Mutations designed to rigidify the conserved regulatory or catalytic spines within the PKDs increased guanylyl cyclase activity, increased sensitivity to natriuretic peptide, or reduced the Michaelis constant in the absence of ATP, consistent with ATP binding stabilizing the PKD in a conformation analogous to that of catalytically active kinases. We conclude that allosteric mechanisms evolutionarily conserved in the PKDs promote the catalytic activation of transmembrane guanylyl cyclases.
Multivariate group-level analysis for task fMRI data with canonical correlation analysis

Task-based functional Magnetic Resonance Imaging (fMRI) has been widely used to determine population-based brain activations for cognitive tasks. Popular group-level analysis in fMRI is based on the general linear model and constitutes a univariate method. However, univariate methods are known to suffer from low sensitivity for a given specificity because the spatial covariance structure at each voxel is not taken entirely into account. In this study, a spatially constrained local multivariate model is introduced for group-level analysis to improve sensitivity at a given specificity for activation detection. The proposed model is formulated in terms of a multivariate constrained optimization problem based on the maximum log likelihood method and solved efficiently with numerical optimization techniques. Both simulated data mimicking real fMRI time series at multiple noise fractions and real fMRI episodic memory data have been used to evaluate the performance of the proposed method. For simulated data, the area under the receiver operating characteristic curves in detecting group activations increases for the subject and group level multivariate method by 20%, as compared to the univariate method. Results from real fMRI data indicate a significant increase in group-level activation detection, particularly in hippocampus, para-hippocampal area and nearby medial temporal lobe regions with the proposed method.
Genetics of alcohol use disorder

Abstract Alcohol use disorder (AUD) is a common and chronic psychiatric disorder characterized by harmful drinking patterns that have substantial negative effects on both personal and public health. Despite its prevalence in society, the underlying pathophysiology of AUD is poorly understood. Although substantial evidence supports a genetic component of the disorder, identification of potential genetic susceptibility factors for AUD has been challenging. Efforts to identify universal genetic risk variants for AUD have included twin, linkage, candidate gene, and genome-wide association studies. Evidence indicates several potential genetic risk variants for AUD, which underscores the complexity and heterogeneity of the disorder. The most consistently identified variants were alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH), the genes of alcohol metabolism. These had protective effects against AUD development. Understanding genetic mechanisms underlying AUD could guide development of targeted pharmacological interventions that would enhance treatment of the disorder.
ED RAPID: A Novel Children's Hospital Direct Admission Process Utilizing the Emergency Department.

Introduction Direct hospital admission of children without evaluation in the emergency department (ED) is common, but few guidelines exist to maximize safety by assessing patient stability. This report describes a novel approach to support patient safety. Methods An interdisciplinary children's hospital team developed a brief ED-based evaluation process called the ED Rapid Assessment of Patients Intended for Inpatient Disposition (ED RAPID). It entails a brief evaluation of vital signs and clinical stability by the ED attending physician and nurse. Children deemed stable are admitted to inpatient wards, whereas those requiring immediate intervention undergo full ED evaluation and disposition. We assessed outcomes for all children evaluated through this process from March 2013 through February 2015. Results During the study period, we identified 715 patients undergoing ED RAPID evaluation. Of these, we directly admitted 691 (96.4%) to the hospital ward after ED RAPID evaluation; median ED treatment time was 4.0 minutes. We transitioned 24 (3.4%) to full ED evaluation, 14 (2.0%) because a ward bed was unavailable, and 10 (1.4%) for clinical reasons identified in the evaluation. We admitted four of the 10 stopped (40% of stops, 0.6% of total) to an intensive care unit, and 6 (60% of stops, 0.8% of total) to the hospital ward after ED care. Eight children (1.1%) admitted to the hospital ward after ED RAPID evaluation required a transfer to an intensive care unit within 12 hours. Conclusion The ED RAPID evaluation process for children directly admitted to the hospital was feasible and effective in this setting.
CAR-NK cells: A promising cellular immunotherapy for cancer

Abstract Natural Killer (NK) cells and CD8+ cytotoxic T cells are two types of immune cells that can kill target cells through similar cytotoxic mechanisms. With the remarkable success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells for treating haematological malignancies, there is a rapid growing interest in developing CAR-engineered NK (CAR-NK) cells for cancer therapy. Compared to CAR-T cells, CAR-NK cells could offer some significant advantages, including: (1) better safety, such as a lack or minimal cytokine release syndrome and neurotoxicity in autologous setting and graft-versus-host disease in allogenic setting, (2) multiple mechanisms for activating cytotoxic activity, and (3) high feasibility for ‘off-the-shelf’ manufacturing. CAR-NK cells could be engineered to target diverse antigens, enhance proliferation and persistence in vivo, increase infiltration into solid tumours, overcome resistant tumour microenvironment, and ultimately achieve an effective anti-tumour response. In this review, we focus on recent progress in genetic engineering and clinical application of CAR-NK cells, and discuss current challenges and future promise of CAR-NK cells as a novel cellular immunotherapy in cancer.
The effect of direct cognitive assessment in the Medicare annual wellness visit on dementia diagnosis rates.

OBJECTIVE To evaluate the relationship between direct cognitive assessment introduced with the Medicare Annual Wellness Visit (AWV) and new diagnoses of dementia, and to determine if effects vary by race. DATA SOURCES Medicare Limited Data Set 5% sample claims 2003-2014 and the HRSA Area Health Resources Files. STUDY DESIGN Instrumental Variable approach estimating the relationship between AWV utilization and new diagnoses of dementia using county-level Welcome to Medicare Visit rates as an instrument. DATA COLLECTION/EXTRACTION METHODS Three hundred twenty-four thousand three hundred and eighty-five fee-for-service Medicare beneficiaries without dementia when the AWV was introduced in 2011. PRINCIPAL FINDINGS Annual Wellness Visit utilization was associated with an increased probability of new dementia diagnosis with effects varying by racial group (categorized as white, black, Hispanic/Latino, or Asian based on Social Security Administration data). Hazard ratios (95% confidence intervals) for new dementia diagnosis within 6 months of AWV utilization were as follows: 2.34 (2.13, 2.58) white, 2.22 (1.71, 2.89) black, 4.82 (2.94, 7.89) Asian, and 6.14 (3.70, 10.19) Hispanic (P < .001 for each). Our findings show that estimates that do not control for selection underestimate the effect of AWV on new diagnoses. CONCLUSIONS Dementia diagnosis rates increased with AWV implementation with heterogenous effects by race and ethnicity. Current recommendations by the United States Preventive Services Task Force state that the evidence is insufficient to recommend for or against screening for cognitive impairment in older adults.
Predictors of long-term weight loss trajectories during a behavioral weight loss intervention: An exploratory analysis.

Background Substantial interindividual variability in response to behavioral weight loss interventions remains a critical challenge in obesity treatment. An improved understanding of the complex factors that contribute to this variability may improve obesity treatment outcomes. Objective To identify weight change trajectories during a behavioral weight loss intervention and to explore differences between trajectory groups in sociodemographic, biologic, behavioral, and psychosocial factors. Methods Adults (n = 170, 40 ± 9 years, BMI 34 ± 4 kg/m2, 84% female) participated in an 18-month behavioral weight loss intervention. Weight was measured at 0, 3, 6, 9, 12, 15, 18, and 24 months. Among participants with at least two weights after baseline (n = 140), clusters of longitudinal trajectories of changes in weight were identified using a latent class growth mixture model. The association between baseline factors or changes in factors over time and trajectory group was examined. Results Two weight change trajectories were identified: "weight regainers" (n = 91) and "weight loss maintainers" (n = 49). Black participants (90%, 19/21) were more likely than non-Black participants to be regainers versus maintainers (p < 0.01). Maintainers demonstrated greater increases in device-measured physical activity, autonomous motivation for exercise, diet self-efficacy, cognitive restraint, and engagement in weight management behaviors and greater reductions in barriers for exercise, disinhibition, and depressive symptoms over 24 months versus regainers (p < 0.05). Conclusion Maintainers and regainers appear to be distinct trajectories that are associated with specific sociodemographic, behavioral, and psychosocial factors. Study results suggest potential targets for more tailored, multifaceted interventions to improve obesity treatment outcomes.
Exploring Social Dynamics of Hard-Disk Drives Circularity with an Agent-Based Approach

By 2025, it is estimated that installed data storage in the U.S. will be 2.2 Zettabytes, generating about 50 million units of end-of-life hard-disk drives (HDDs) per year. The circular economy (CE) tackles waste issues by maximizing value retention in the economy, for instance, through reuse and recycling. However, the reuse of hard disk drives is hindered by the lack of trust organizations have toward other means of data removal than physically destroying HDDs. Here, an agent-based approach explores how organizations' decisions to adopt other data removal means affect HDDs' circularity. The model applies the theory of planned behavior to model the decisions of HDDs end-users. Results demonstrate that the attitude (which is affected by trust) of end-users toward data-wiping technologies acts as a barrier to reuse. Moreover, social pressure can play a significant role as organizations that adopt CE behaviors can set an example for others.
Brain Abscess Caused by Bordetella hinzii.

A 60 year-old well-travelled botanist with a history of chronic sinusitis and treated stage IV follicular lymphoma presented to an outside facility with two weeks of progressive headache and nausea.
Fabricating Futures: Envisioning Scenarios for Home Fabrication Technology

Making and Maker culture are growing at such prodigious speed that there are very few people whose lives aren’t touched by them, even if they don’t realize it. The scope of activities and practices that fit under the heading of Maker Culture is vast: woodworking, electronic prototyping, robotics, urban farming, software development, fire-art, weaving, circuit-bending, citizen science, prop-making, cosplay, reenactment, soapbox racer rallies, home genetic sequencing, bio-art, homesteading, knitting, rocketry, and many other more obscure practices all fit inside the “tent” of Making. Making is many things: it is a practice, a set of values, a culture and a community, a return to the past, an embracing of the future, and a new mode of production and consumption. While much of the best making involves a return to lost handcrafts and traditional “boutique” production techniques, one cannot underestimate the impact of recent innovations in small-scale fabrication technologies. Machines that used to only be available at industrial scales, at prices that could only be borne by large corporations, are now becoming accessible to the home Maker. And some machines, like 3D printers, are creating new workflows and prototyping processes that defy traditional industrial production methods.
Can tranexamic acid change preoperative anemia management during total joint arthroplasty

AIM: To investigate the postoperative transfusion and complication rates of anemic and nonanemic total joint arthroplasty patients given tranexamic acid (TXA). METHODS: A cross-sectional prospective study was conducted of primary hip and knee arthroplasty cases performed from 11/2012 to 6/2014. Exclusion criteria included revision arthroplasty, bilateral arthroplasty, acute arthroplasty after fracture, and contraindication to TXA. Patients were screened prior to surgery, with anemia was defined as hemoglobin of less than 12 g/dL for females and of less than 13 g/dL for males. Patients were divided into four different groups, based on the type of arthroplasty (total hip or total knee) and hemoglobin status (anemic or nonanemic). Intraoperatively, all patients received 2 g of intravenous TXA during surgery. Postoperatively, allogeneic blood transfusion (ABT) was directed by both clinical symptoms and relative hemoglobin change. Complications were recorded within the first two weeks after surgery and included thromboembolism, infection, and wound breakdown. The differences in transfusion and complication rates, as well as the relative hemoglobin change, were compared between anemic and nonanemic groups. RESULTS: A total of 232 patients undergoing primary joint arthroplasty were included in the study. For the total hip arthroplasty cohort, 21% (18/84) of patients presented with preoperative anemia. Two patients in the anemic group and two patients in the nonanemic group needed ABTs; this was not significantly different (P = 0.20). One patient in the anemic group presented with a deep venous thromboembolism while no patients in the nonanemic group had an acute complication; this was not significantly different (P = 0.21). For nonanemic patients, the average change in hemoglobin was 2.73 ± 1.17 g/dL. For anemic patients, the average change in hemoglobin was 2.28 ± 0.96 g/dL. Between the two groups, the hemoglobin difference of 0.45 g/dL was not significant (P = 0.13). For the total knee arthroplasty cohort, 18% (26/148) of patients presented with preoperative anemia. No patients in either group required a blood transfusion or had an acute postoperative complication. For nonanemic patients, the average change in hemoglobin was 1.85 ± 0.79 g/dL. For anemic patients, the average change in hemoglobin was 1.09 ± 0.58 g/dL. Between the two groups, the hemoglobin difference of 0.76 g/dL was significant (P < 0.001). CONCLUSION: TXA administration results in low transfusion and complication rates and may be a useful adjunct for TJA patients with preoperative anemia.
In vivo tumor growth induces DNA damage in distal organs

1888 Cancer biomarkers are helpful for early tumor diagnostics, cancer management, and prognosis of tumor outcome and recurrence. Current advances in cancer biology associate DNA damage with genome instability and oncogenic transformation and introduce the possibility of using DNA damage-associated proteins as cancer biomarkers. The bystander effect, in which directly irradiated cells transmit signals that induce DNA damage in unirradiated neighbors, is now well established. We recently found that various other sources of cell stress, including media from cancerous cells, resulted in histone H2AX phosphorylation in normal human cell cultures, which is one of the first responses to DNA DSBs. This suggests that the bystander effect may be part of a more general cellular stress response. Previous studies have also shown higher levels of closely spaced (clustered) oxidative DNA lesions (OCDLs) in mouse tissues not-directly exposed to X-rays and in cell cultures, implying a possible bystander effect. We hypothesized that tumors growing in vivo may induce DNA damage in normal organs and peripheral blood mononuclear cells of the host, as a consequence of the bystander effect or induction of oxidative stress, and phosphorylated H2AX (γ-H2AX) and/or OCDLs can serve as a common indicator of this stress. To test this hypothesis, 6 C57BL/6NCr mice from the Animal Production Area, NCI-Frederick, were subcutaneously injected with B16 melanoma cells obtained from the DCTD tumor repository, NCI (test cohort). As controls, 6 mice were left untreated (negative control cohort), and 6 additional mice were injected with a Freund’s adjuvant (inflammatory response control cohort). Tumor growth was monitored until tumor size approached 300 mg, after which the animals were sacrificed. Duodenum, liver, kidney, lung and ovary were touch-printed and sectioned; spleen and blood lymphocytes were isolated and cytospun. The presence and numbers of nuclear γ-H2AX foci were measured by immunofluorescent staining. γ-H2AX focal incidences increased in the duodenum of tumor-bearing mice (2.3 foci per cell (fpc) vs. 1 fpc in negative control and 0.9 in inflammatory response control cohorts; p in vivo in this study, our observations have wider implications for understanding how tumor microenvironment contributes to accumulation of stress-related DNA damage, genome instability and carcinogenesis.
PARMÉNIDES GARCÍA SALDAÑA: LIKE A ROLLING STONES

A pesar de que la obra de Parmenides Garcia Saldana (1944-1982) es mencionada en casi cada referencia a la Literatura de la Onda de los anos 60, ha recibido poca atencion de la critica. Su obra, como es el caso de otros escritores de la Onda, es notable por ser entre la primera en ser influenciada profundamente por los efectos de la globalizacion; particularmente por la musica y cultura del rock y, mas especificamente, los Rolling Stones. Aunque se puede notar varios modelos literarios de los que se nutre, como Arthur Rimbaud y la Generacion Beat (en concreto los escritos de William S. Burroughs y su novela Naked Lunch (1959)), la influencia mas prominente en su unica novela, Pasto verde (1968), es sin duda los Rolling Stones. Las referencias al grupo, canciones especificas, y su modo iconoclasta de ser sirven no solo para evocar la epoca en que se situa la novela, sino que sirven como elementos semanticos claves dentro del texto experimental. El uso particular de la cancion “Satisfaction” en el texto sirve como una guia para entender la psiquis del narrador y la vision del mundo subjetivo que esta construyendo textualmente. El narrador, que sirve como doble de Garcia Saldana mismo, es una construccion textual del autor mismo y la perspectiva que tiene de su propia realidad caotica: repleta de las esperanzas, las proyecciones y las decepiones experimentadas por Garcia Saldana en la epoca.
International Relations and Responsibility in an Increasingly Unequal World

Martha Nussbaum has provided a major service to the study and practice of international relations (IR) by articulating the moral claims made on states and international organizations by the fact of human capabilities. In return, something of what has been learned by scholars of IR can contribute to her project by considering the ways in which concrete international institutions (such as UNDP) have struggled with their international responsibilities, highlighting the role of egalitarian social movements in the establishment and reform of global level intergovernmental organizations, and searching for ways to embody Nussbaum's ‘Principles for Global Structure’ in the current agenda for reform of the United Nations' system.
Analysis of the innate and adaptive phases of allograft rejection by cluster analysis of transcriptional profiles

Both clinical and experimental observations suggest that allograft rejection is a complex process with multiple components that are, at least partially, functionally redundant. Studies using graft recipients deficient in various genes including chemokines, cytokines, and other immune-associated genes frequently produce a phenotype of delayed, but not indefinitely prevented, rejection. Only a small subset of genetic deletions (for example, TCRα or β, MHC I and II, B7-1 and B7-2, and recombinase-activating gene) permit permanent graft acceptance suggesting that rejection is orchestrated by a complex network of interrelated inflammatory and immune responses. To investigate this complex process, we have used oligonucleotide microarrays to generate quantitative mRNA expression profiles following transplantation. Patterns of gene expression were confirmed with real-time PCR data. Hierarchical clustering algorithms clearly differentiated the early and late phases of rejection. Self-organizing maps identified clusters of coordinately regulated genes. Genes up-regulated during the early phase included genes with prior biological functions associated with ischemia, injury, and Ag-independent innate immunity, whereas genes up-regulated in the late phase were enriched for genes associated with adaptive immunity.
Automation of the Indirect Fluorescent-Antibody Test for Toxoplasmosis

The feasibility of automating the decision-making tasks of the medical technician in the determination of the results of the indirect fluorescent-antibody test for toxoplasmosis was investigated. Two approaches were studied: (i) macroscopic measurement of fluorescence from a large number of organisms (full-field illumination measurements), and (ii) microscopic measurements of fluorescence and morphology of individual parasites (pattern recognition). The macroscopic approach was studied utilizing an argon-ion laser in incident illumination with a Leitz Ortholux microscope and a phototube mounted so as to measure green fluorescence. Due to similar amounts of fluorescence from negative polar reactions and positive rim reactions, the macroscopic technique was concluded to be not feasible. The microscopic approach was studied utilizing a high resolution optical pattern recognition instrument. The results indicate that an object area measurement is sufficient to distinguish the presence of Toxoplasma gondii organisms from debris and overlapping organisms when studying the red fluorescence (due to Evans blue counterstain). Dark reactions were determined by the absence of green fluorescence. The differentiation of the rim and polar reactions was determined by the measurement of the ratio of green fluorescing area (due to fluorescein isothiocyanate) to red fluorescing area on the same organism. Clinically important titer information was also demonstrated to be obtainable. It was concluded that complete automation of the indirect fluorescent antibody test for toxoplasmosis is feasible with existing technology.
Age dependent regulation of bone-mass and renal function by the MEPE ASARM-motif

Abstract Context Mice with null mutations in matrix extracellular phosphoglycoprotein (MEPE) have increased bone mass, increased trabecular density and abnormal cancellous bone (MN-mice). These defects worsen with age and MEPE overexpression induces opposite effects. Also, genome wide association studies show that MEPE plays a major role in bone mass. We hypothesized that the conserved C-terminal MEPE ASARM-motif is chiefly responsible for regulating bone mass and trabecular structure. Design To test our theory we overexpressed C-terminal ASARM-peptide in MN-mice using the Col1α1 promoter (MNAt-mice). We then compared the bone and renal phenotypes of the MNAt-mouse with the MN-mouse and the X-linked hypophosphatemic rickets mouse (HYP). The HYP mouse overexpresses ASARM-peptides and is defective for the PHEX gene. Results The MN-mouse developed increased bone mass, bone strength and trabecular abnormalities that worsened markedly with age. Defects in bone formation were chiefly responsible with suppressed sclerostin and increased active β-catenin. Increased uric acid levels also suggested that abnormalities in purine-metabolism and a reduced fractional excretion of uric acid signaled additional renal transport changes. The MN mouse developed a worsening hyperphosphatemia and reduced FGF23 with age. An increase in the fractional excretion of phosphate (FEP) despite the hyperphosphatemia confirms an imbalance in kidney–intestinal phosphate regulation. Also, the MN mice showed an increased creatinine clearance suggesting hyperfiltration. A reversal of the MN bone–renal phenotype changes occurred with the MNAt mice including the apparent hyperfiltration. The MNAt mice also developed localized hypomineralization, hypophosphatemia and increased FGF23. Conclusions The C-terminal ASARM-motif plays a major role in regulating bone-mass and cancellous structure as mice age. In healthy mice, the processing and release of free ASARM-peptide are chiefly responsible for preserving normal bone and renal function. Free ASARM-peptide also affects renal mineral phosphate handling by influencing FGF23 expression. These findings have implications for understanding age-dependent osteoporosis, unraveling drug-targets and developing treatments.
Infection by Bacteriophage P1 and Development of Host-controlled Restriction and Modification and of Lysogenic Immunity

Abstract Shigella dysenteriae cells were infected with phage P1 or P1cl. The outcome of superinfection of these cells with phage T1.Sh or T1.Sh(P1) or P1cl was studied as a function of time after the initial infection. Cells undergoing either a lytic response or a lysogenic response to the primary infection develop the ability to specifically restrict T1.Sh between 30 and 45 min. Between 15 and 30 min, the cells seem to develop the ability to produce T1.Sh(P1) after infection by T1.Sh. However, reasons are given for believing that this apparent time difference is consistent with a simultaneous development of the two capacities (restriction and modification) within the cell. This development occurs between 30 and 45 min. Cells infected with P1cl and superinfected 45 or more min later with T1.Sh(P1) can yield both P1cl and T1. Cells infected with P1 become resistant to infection by P1cl within 5 to 10 min. It is argued that this early immunity is not necessarily different in mechanism from true lysogenic immunity.
Regulation of cell death in flower petals

The often rapid and synchronous programmed death of petal cells provides a model system to study molecular aspects of organ senescence. The death of petal cells is preceded by a loss of membrane permeability, due in part to increases in reactive oxygen species that are in turn related to up-regulation of oxidative enzymes and to a decrease in activity of certain protective enzymes. The senescence process also consists of a loss of proteins caused by activation of various proteinases, a loss of nucleic acids as nucleases are activated, and enzyme-mediated alterations of carbohydrate polymers. Many of the genes for these senescence-associated enzymes have been cloned. In some flowers, the degradative changes of petal cells are initiated by ethylene; in others, abscisic acid may play a role. External factors such as pollination, drought and temperature stress also affect senescence, perhaps by interacting with hormones normally produced by the flowers. Signal transduction may involve G-proteins, calcium activity changes and the regulation of protein phosphorylation and dephosphorylation. The efficacy of the floral system as well as the research tools now available make it likely that important information will soon be added to our knowledge of the molecular mechanisms involved in petal cell death.
Carnitine Absorption: Effects of Sodium Valproate and Sodium Octanoate in the Caco-2 Cell Culture Model of Human Intestinal Epithelium

The Caco-2 cell culture system was used as a model to investigate the mechanism of carnitine absorption in human small intestinal epithelium, and to determine if valproic acid inhibits this process in the model system. The hypotheses tested were: Carnitine is absorbed by a mechanism not involving carrier-mediated transport; and valproic acid specifically inhibits carnitine absorption. Results of the investigation were consistent with exclusively passive, paracellular absorption of carnitine across the Caco-2 cell monolayer. Saturable and structure-specific intracellular accumulation of carnitine from the apical medium was observed, but was independent of the process of absorption. At high concentration (10 mmol/L), both sodium valproate and its straight-chain analog sodium octanoate inhibited cellular accumulation of carnitine from the apical medium, but enhanced transmonolayer passage of carnitine from the apical to the basal medium. Lower concentrations of these organic acid salts (0.1 or 1 mmol/L) did not affect cellular accumulation of carnitine, but at 1 mmol/L concentration, they slightly enhanced transmonolayer flux. Paradoxically, cells cultured for 5 days in the presence of sodium valproate or sodium octanoate accumulated carnitine at a faster rate than cells cultured in the absence of these compounds. It is concluded that carnitine is absorbed across the Caco-2 monolayer by a passive, paracellular route that is not inhibited by sodium valproate.
The Rule of L aw and the Importance of Procedure

Proponents of the rule of law argue about whether that ideal should be conceived formalistically or in terms of substantive values. Formalistically, the rule of law is associated with principles like generality, clarity, prospectivity, consistency, etc. Substantively, it is associated with market values, with constitutional rights, and with freedom and human dignity. In this paper, I argue for a third layer of complexity: the procedural aspect of the rule of law; the aspects of rule-of-law requirements that have to do with "natural Justice" or "procedural due process." These I believe have been neglected in the jurisprudential literature devoted specifically to the idea of the rule of law and they deserve much greater emphasis. Moreover procedural values go beyond elementary principles like the guarantee of an unbiased tribunal or the opportunity to present and confront evidence. They include the right to argue in a court about what the law is and what its bearing should be on one's situation. The provision that law makes for argument is necessarily unsettling, and so this emphasis on the procedural aspect highlights the point predictability should not be regarded as the be-all and end-all of the rule of law.
Multiscale Computational Characterization

To understand, predict, and control matter and energy at the electronic, atomic, molecular, microstructural, and continuum levels, scientists need to investigate materials at a combination of length and time scales that are characteristic to relevant physical and chemical phenomena. As a consequence, experimental, theoretical, and computational methods must cover a wide range of space and time scales, starting with the nucleus and the electronic structure of individual or clustered atoms (A), to nano/microstructural features, all the way to continuum properties of the sample (cm). Along the time scale, the investigation domain ranges from excitations (ps) to nucleation of new phases (ns), all the way to diffusion (minutes, hours) and aging characteristic times (months, years). The article briefly reviews the major theoretical and computational methods used in multiscale characterization of materials, including atomistic (DFT, MD, AIMD, kMC), mesoscale (PF, DD, DDD), and continuum (FEM, FDM, FVM, CALPHAD) methods. Method coupling schemes are also discussed, from sequential to loose and tight concurrent coupling and ending with hybrid coupling methods. The multiscale characterization methodology is illustrated with results of simulations phenomena in Li-ion and UO2 materials. The chapter ends with a discussion of challenges and opportunities in the multiscale characterization of materials. Keywords: computational characterization and microscopy; multiscale models and simulations; scale coupling; verification and validation
Free bilirubin concentrations and bilirubin-binding affinity in term and preterm infants*

Free bilirubin concentration, bilirubin-binding capacity, and bilirubin-binding affinity were determined hy peroxidase oxidation in 66 newborn infants. Twelve healthy term infants whose unconjugated bilirubin concentration was 15.8±3.7 mg/dl (mean±SD) had a binding capacity of 31.9±3.7 mg/dl (bilirubin: albumin molar ratio=0.89±0.07) and Ka=28±11×10 7 /M. Twelve term infants with clinical complications of asphyxia, acidosis, respiratory distress, or sepsis, and 17 preterm infants with no complications had lower serum albumin concentrations and slightly reduced binding capacity and affinity compared to the healthy term infants. Free bilirubin concentrations were similar in these three groups, averaging 8 to 9 nmol/l in each group. Twenty-five preterm infants with complications had significantly higher free bilirubin (19±11 nmol/l), lower binding capacity, and lower binding affinity than any of the other three groups (P
Bird Control at Airports

Birds are a serious threat to aircraft, particularly near airports. For civil aircraft about 75% of all bird-strikes occur near airports. Gulls and small flocking-birds provide the greatest threat to aircraft near airports. Birds are attracted to airports because they become habituated to the noise and traffic, and are attracted by the presence of areas for roosting, loafing, and feeding. Serious bird-strikes can be reduced around airports by reducing the number of birds, by making the birds get out of the way of airplanes, by having planes avoid birds, by adding physical protection to the airplanes, and by switching to new types of aircraft which are safer with respect to bird-strikes. The first two solutions involve bird control, while the last three involve modification of aircraft or aircraft routes. Airport personnel are usually involved only in controlling bird numbers or in dispersing them from the airport.
Transient response of velocity fluctuations in inertialess channel flows of viscoelastic fluids

We examine transient responses of velocity fluctuations in inertialess channel flows of viscoelastic fluids. Such fluids have broad applications in modern technology including the design and control of polymer processing operations and the development of strategies to efficiently mix fluids in microfluidic devices. For streamwise-constant three-dimensional fluctuations, we demonstrate analytically the existence of initial conditions that lead to quadratic scaling of the kinetic energy density with the Weissenberg number, We. This illustrates that in strongly elastic channel flows of viscoelastic fluids, velocity fluctuations can exhibit significant transient growth even in the absence of inertia. Furthermore, we show that the fluctuations in streamwise velocity achieve O(We) growth over a time scale O(We) before eventual asymptotic decay. We also demonstrate that the large transient responses originate from the stretching of polymer stress fluctuations by a background shear and draw parallels between streamwise-constant inertial flows of Newtonian fluids and streamwise-constant inertialess flows of viscoelastic fluids.
A proof of concept trial of an online psychoeducational program for relatives of both veterans and civilians living with schizophrenia.

Objectives Family psychoeducation has been found to reduce relapse in schizophrenia but penetration rates are low. In this study, we evaluate the feasibility of an online multifamily group program for relatives of persons with schizophrenia that can be accessed from participants' homes. Methods We explored participation rates and evaluations of a 12-month multimodal website intervention. Using a quasi-experimental design, we compared illness outcomes (factors on the Brief Psychiatric Rating Scale, hospitalizations) of persons with diagnosed schizophrenia, and relative distress outcomes (somatic concerns and anxiety/depression subscales on the Brief Symptom Inventory) from relatives participating in the intervention (n = 26) to archival data we had from comparable dyads who received customary care (n = 16). Results The majority of participants in the program attended more than half the core online support sessions, expressed high levels of satisfaction, and found the technology easy to access. There appeared to be little impact of online participation on clinical status of persons with schizophrenia or relatives' distress, although there was a trend for fewer hospitalizations in the online group. Small sample size is a factor in interpreting results. Conclusions Online interventions for relatives of persons with schizophrenia, while feasible, present unique challenges. These include 1) assuring access to the intervention in populations who do not own a computer; 2) addressing privacy concerns; 3) overcoming the special challenges of conducting groups in real time; 4) managing emergent situations adequately; and 5) questions about efficacy.
Successful treatment of major depression: the effects of positive and negative life events on time to remission

The relationships of stressful and of positive events to treatment response for depression have typically been studied separately using methods based on the rates of events and ultimate remission status. A novel data-analytic approach was introduced that addresses the limitations of these ad hoc methods and provides more power for detecting effects of life events and other prognostic factors on treatment response. Survival methodology with time-varying covariates was used to delineate the simultaneous but separate effects of positive and negative aspects of life events occurring both prior to and during treatment among patients treated with interpersonal psychotherapy (IPT) alone or IPT followed with adjunctive fluoxetine or imipramine for recurrent unipolar depression. Somewhat surprisingly, stressful events were not significantly related to response time, but neutral events during treatment were related to a prolonged time to remission both alone in univariate analysis and when considered along with other life-event and prognostic covariates in multiple regression analyses. Positive events during treatment did not relate to remission, but those occurring on average 24 weeks prior to remission were associated with more rapid remission in univariate analysis. Other significant correlates of remission included endogeneity, which consistently related to more rapid remission. Overall, these results underscore the importance of studying events, including seemingly neutral and temporally distal experiences, and support the use of the novel methodology in studying the impact of major life events and other prognostic factors on remission of depressive disorder. Copyright © 2000 Whurr Publishers Ltd.
Metamorphism: Water from stone

Where the Pacific and Australian tectonic plates collide under the South Island of New Zealand large quantities of aqueous fluid are produced. But how does this happen? Geophysical and petrological data indicate that it may not be as we thought.
The pathogenesis of vesicular stomatitis virus, serotype Indiana, in Aedes aegypti mosquitoes, after imbibition of a viremic blood meal.

This study showed that Vesicular Stomatitis Virus (Indiana) in most instances was not capable of replicating inAedes aegypti when imbibed by the mosquitoes on a viremic host. Rapid inactivation of the virus was observed in some cases within 24 hours after imbibition. Attempts to demonstrate virus inactivation by midgut contentsin vitro were not successful.
Biochemical events associated with healing of a chemical injury in the rabbit lens.

Intracameral injection of methylene blue causes a lenticular injury, the healing of which is associated with increased mitosis. Biochemical events associated with the cell cycle of lens epithelium in the in vivo system have been studied and compared to their in vitro counterparts. We have observed enhanced binding of [3H]actinomycin D together with subsequent increases in RNA and protein labeling. The behavior of chromosomal proteins was also studied. The banding pattern for histone and nonhistone chromosomal proteins remained qualitatively unchanged at all times studied.
Evaluation of trends in derived snowfall and rainfall across Eurasia and linkages with discharge to the Arctic Ocean

[1] To more fully understand the role of precipitation in observed increases in freshwater discharge to the Arctic Ocean, data from a new archive of bias-adjusted precipitation records for the former USSR (TD9813), along with the CRU and Willmott-Matsuura data sets, were examined for the period 1936–1999. Across the six largest Eurasian river basins, snowfall derived from TD9813 exhibits a strongly significant increase until the late 1950s and a moderately significant decrease thereafter. A strongly significant decline in derived rainfall is also noted. Spatially, snowfall increases are found primarily across north-central Eurasia, an area where the rainfall decreases are most prominent. Although no significant change is determined in Eurasian-basin snowfall over the entire 64 year period, we note that interpolation from early, uneven station networks causes an overestimation of spatial precipitation, and that the local snowfall trends determined from gridded TD9813 data are likely underestimated. Yet, numerous uncertainties in historical Arctic climate data and the sparse, irregular nature of Arctic station networks preclude a confident assessment of precipitation-discharge linkages during the period of reported discharge trends.
Regulation of Apoptosis by Presenilin 1

Familial Alzheimer's disease is transmitted as an autosomal dominant disorder and, in 5-10% of the cases, is caused by mutations in the coding regions of two homologous genes, Presenilin 1 and 2 (PS1 and PS2). Previously, we have shown that PS2, a homolog of PS1. regulates apoptosis induced in neurons by trophic withdrawal or Abeta, and in T-cells by Fas ligand. We now report that PS1 also regulates apoptosis. Both wild-type and the H115Y mutant form of PS1 enhance Fas-mediated apoptosis in Jurkat cells. We also observed that wild-type and the H115Y mutant form of PS1 differentially regulate Jun Kinase, an important enzyme regulating apoptosis.
Investigation of primary fine particulate matter from coal combustion by computer-controlled scanning electron microscopy

The particle size distributions, morphologies, and chemical composition distributions of 14 coal fly ash (CFA) samples produced by the combustion of four western U.S. coals (two subbituminous, one lignite, and one bituminous) and three eastern U.S. coals (all bituminous) have been examined by computer-controlled scanning electron microscopy (CCSEM). The samples were obtained from a 50-kW combustor using an isokinetic sampler and separated aerodynamically using a cyclone into PM fractions that were nominally 2.5 μm in mean diameter (PM 2.5 + ). However, the CCSEM particle size distribution results show that particles with mean diameter 2.5 μm account for over 80% of the total particle volume for both the PM 2.5 and the PM 2.5 + fractions. The samples contained from 0.5 to 11.0 wt.% of unburned carbon and carbonaceous PM was the dominant form of PM < 1 μm in mean size. Typically, over 80% of carbon-rich PM was < 1 μm and over 95% was <2.5 μm in mean size. The dominant carbonaceous PM morphology consisted of roughly spherical carbon particulates ∼ 10-50 nm in diameter bonded together in complex chains and clusters that were usually < 1 μm in size. Glassy phases with rounded and frequently spherical morphologies were the dominant species observed for the inorganic PM. Particle compositions for several hundred inorganic particles are presented as ternary diagrams, which appear to be useful for source attribution. The inorganic PM derived from combustion of western low-rank coals, which are rich in carboxyl-bound Ca, is dominated by Ca-Si-Al glass phases, while that from eastern bituminous coals, which are rich in pyrite, is dominated by Fe-Si-Al glass phases. Important secondary signature glass phases that are also revealed by the ternary diagrams are Na-Si-Al for western CFA and K-Si-Al for eastern CFA.
Off-pump coronary artery bypass grafting does not decrease the incidence of atrial fibrillation.

Abstract Background Postoperative atrial fibrillation remains a significant source of morbidity after coronary artery bypass grafting. We reviewed the data on 2,569 patients to determine if the absence of cardiopulmonary bypass resulted in a lower incidence of atrial fibrillation. Methods All patients undergoing coronary artery bypass grafting without cardiopulmonary bypass from January 1, 1997 through June 30, 2001 were evaluated for postoperative atrial fibrillation. The data of 252 patients with no cardiopulmonary bypass (group 1) were reviewed and compared with three other patient groups. Group 2 consisted of 1,470 patients using cardiopulmonary bypass during the same study period. Group 3 consisted of 841 patients with a similar number of grafts as the study group but using cardiopulmonary bypass. Group 4 consisted of historical data for 847 patients operated on using cardiopulmonary bypass collected from January 1995 through December 1996. Prophylactic β-blockade was instituted in January 1997. Groups 1 to 3 received this treatment, but group 4 did not. Results Group 1 had an incidence of atrial fibrillation of 8.8%. Groups 2, 3, and 4 had incidences of atrial fibrillation of 11.6%, 9.4%, and 28.0%, respectively. When compared with group 1, the incidence of atrial fibrillation in group 4 was statistically different ( p Conclusions Avoiding cardiopulmonary bypass did not aid the reduction of atrial fibrillation at our institution.
OBSERVATION: REDISCOVERING HISTORICAL GEOGRAPHY IN THE LAND OF NORUMBEGA

Recent appraisals of historical geography range widely in their assessment of the field. Donald Meinig (1989), writing of ‘The Historical Geography Imperative,’ concludes: ‘historical geography is not, has never been, just another item in the proliferating diversity of our grand enterprise. Rather, like physical and environmental geography, it is one of the foundations of the whole enterprise. In its own way historical geography encompasses and contributes to all of geography. Micheal Dear (1988) disagrees. In ‘The postmodern challenge: Reconstructing human geography,’ he states that historical geography is ‘overde-termined,’ and ‘an empty concept' conveying ‘few (if any) significant analytical distinctions …. He concludes that historical geography does ‘little more than confirm what geography is about. Both writers agree on the pervasive and comprehensive nature of historical geography, but Dear sees this inclusiveness as more of a cincture, whereas Meinig conveys the fundamental and embracing understanding of geography inherent in the practice of historical geography.