bluuebunny/crossref_metadata_2025_split huggingface dataset:
The response of glaciers to intrinsic climate variability: observations and models of late-Holocene variations in the Pacific Northwest
Authors: Roe Gerard H. , O’Neal Michael A. 
Published: December 2009

AbstractDiscriminating between glacier variations due to natural climate variability and those due to true climate change is crucial for the interpretation and attribution of past glacier changes, and for the expectations of future changes. We explore this issue for the well-documented glaciers of Mount Baker in the Cascades Mountains of Washington State, USA, using glacier histories, glacier modeling, weather data and numerical weather model output. We find that natural variability alone is capable of producing kilometer-scale excursions in glacier length on multi-decadal and centennial timescales. Such changes are similar in magnitude to those attributed to a global Little Ice Age. The null hypothesis, that no climate change is required to explain the glacier fluctuations in this setting, cannot be rejected. These results for Mount Baker glaciers are also consistent with an earlier study analyzing individual glaciers in Scandinavia and the Alps. The principle that long-timescale fluctuations of glacier length can be driven by short-timescale fluctuations in climate reflects a robust and fundamental property of stochastically forced physical systems with memory. It is very likely that this principle also applies to other Alpine glaciers and that it therefore complicates interpretations of the relationship between glacier and climate history. However, the amplitude and timescale of the length fluctuations depends on the details of the particular glacier geometry and climatic setting, and this remains largely unevaluated for most glaciers.
Observed runoff, jökulhlaups and suspended sediment load from the Greenland ice sheet at Kangerlussuaq, West Greenland, 2007 and 2008
Authors: Mernild Sebastian H. , Hasholt Bent 
Published: December 2009

AbstractThis study fills the gap in hydrologic measurements of runoff exiting a part of the Greenland ice sheet (GrIS), the Kangerlussuaq drainage area, West Greenland. The observations are of value for obtaining knowledge about the terrestrial freshwater and sediment output from part of the GrIS and the strip of land between the ice sheet and the ocean, in the context of varying ice-sheet surface melt and influx entering the ocean. High-resolution stage, discharge and suspended sediment load show a decrease in runoff of ∼25% and in sediment load of ∼40% from 2007 to 2008 in response to a decrease in the summer accumulated number of positive degree-days. During the 2007 and 2008 runoff seasons, jökulhlaups were observed at Kangerlussuaq, drained from an ice-dammed lake at the margin of the GrIS.
Methanesulphonic acid loss during ice-core storage: recommendations based on a new diffusion coefficient
Authors: Roberts Jason L. , Van Ommen Tas D. , Curran Mark A.J. , Vance Tessa R. 
Published: December 2009

AbstractThe loss of methanesul phonic acid (MSA) from stored ice cores can be significant over typical storage times, with diffusion to the ice-core surface controlling the loss. Methods for minimizing this loss are discussed and it is shown how measurements can be corrected by calculating the amount of MSA lost. A revised diffusion coefficient for MSA in solid ice, (4.1 × 10−13) ± (2.5 × 10−14) m2 s−1, is derived to improve such MSA loss corrections.
Transient response of idealized glaciers to climate variations
Authors: Lüthi Martin P. 
Published: December 2009

AbstractThe transient response of glaciers to climate variations is investigated with a novel low-order model of an idealized glacier resting on uniformly inclined bedrock. The model consists of two volumes representing the accumulation and ablation areas, which are joined by a flux gate controlling mass flow according to the shallow-ice approximation. Under the assumption of a constant vertical mass-balance gradient, a volume–length scaling relation is derived which depends explicitly on mass-balance gradient and bedrock slope. Analytic expressions for the volume and area timescales are given, which are inversely proportional to the mass-balance gradient and a geometric factor which is the ratio between the vertical extent of the ablation area and the ice thickness at the equilibrium line. From the low-order model, a dynamical system in length and volume is obtained. Results from this system are in good agreement with solutions obtained from a transient finite-element model solving the full force-balance and mass-conservation equations. Under periodic forcing there are significant deviations of the length response, which show that the usual relaxation-type parameterization of length change is not well suited for short-term reactions. Switching on and off periodic climate forcing, the model glaciers show surprisingly large initial and final transient responses that have not been investigated before. These results are of significance for the interpretation of length and thickness changes observed on glaciers.
Design Issues for Socially Intelligent User Interfaces
Authors: McVittie C. , Reiter E. , Freer Y. , Sykes C. , Logie R. , McKinlay A. 
Published: December 2009

Summary
Objectives: This study aims to demonstrate the usability of discourse analyses as a means of evaluating medical informatics systems by examining one particular computer-based data-to-text system for delivering neonatal health care information.
Methods: Six textual summaries of clinical information, three produced by human clinicians and three by the data-to-text system, were subjected to fine-grain discourse analysis. Analysis was performed ‘blind’ on all six textual summaries. Analysis focused on the identification of lexical items and on the potential effects of these items on users of these clinical information summaries.
Results: Results showed that there were clear differences between human- and system-generated clinical summaries, with human clinicians providing better narrative flow and textual detail. The data-to-text system successfully produced textual summaries although it fell short of human abilities.
Conclusions: These results indicate potential future improvements to the system. Discourse analysis as used here may offer significant advantages in evaluating and developing similar medical informatics systems.
Auditory Steady-State Responses and Speech Feature Discrimination in Infants
Authors: Cone Barbara , Garinis Angela 
Published: December 2009

Purpose: The aim of this study was to determine whether there was a correlation between auditory steady-state responses (ASSRs) for complex toneburst stimuli and speech feature discrimination (SFD) abilities in young infants. Study Sample: Seventeen infants (mean age =
9.4 months) and 21 adults (mean age = 27 years) with normal hearing had ASSR and SFD tests. Data Collection: The ASSR test employed an eight-component complex toneburst stimulus; threshold and input‐output functions were determined as level was systematically varied.
The SFD test utilized an observer-based, visual-reinforcement test procedure to determine the infant's ability to detect the speech feature change from /ba/ to /da/. Results: The correlation of the group mean /ba/‐/da/ discrimination performance (percent correct) with the group
mean ASSR score (percent responses present) ranged from r = 0.64 for the 1500 Hz amplitude-modulated and frequency-modulated tone burst to 0.99 for ASSRs for all stimulus components; however, correlations between ASSRs and SFD scores for individual subjects were modest.
Conclusion: The ASSR and SFD results appear to reflect the audibility of the stimuli.
Susceptibility to Genital Herpes as a Biomarker Predictive of Increased HIV Risk: Expansion of a Murine Model of Microbicide Safety
Authors: Wilson Sarah S , Cheshenko Natalia , Fakioglu Esra , Mesquita Pedro MM , Keller Marla J , Herold Betsy C 
Published: December 2009

Background A crucial gap in the development of microbicides for HIV prevention is the absence of models predictive of safety. Previous studies have demonstrated an increased susceptibility to genital herpes in mice following repeated applications of nonoxynol-9 (N-9). This study was designed to explore the underlying mechanisms, focusing on the effects that N-9 has on genital tract epithelium and to apply this expanded model to evaluate the safety of microbicides that have been advanced to clinical trials. Methods Mice were treated intravaginally with formulated 3.5% N-9, 1% tenofovir, 0.5% or 2% PRO 2000, hydroxyethylcellulose (HEC) placebo or no treatment and the effect on herpes simplex virus 2 (HSV-2) susceptibility, epithelial cell architecture, junctional proteins and inflammation were assessed. Results Mice treated with seven daily doses of N-9, but not tenofovir, PRO 2000 or HEC, were significantly more susceptible to challenge with low doses of HSV-2; confocal microscopy demonstrated increased numbers of viral particles deep within the genital tract. N-9 disrupted the epithelium with loss of tight and adherens junctional proteins. By contrast, the epithelium was relatively preserved following tenofovir, PRO 2000 and HEC exposure. Additionally, N-9, but not the other microbicides, triggered a significant inflammatory response relative to untreated mice. Conclusions These findings indicate that disruption of the epithelium contributes to increased HSV-2 susceptibility and might provide a biomarker predictive of increased risk for HIV acquisition. The results are consistent with the safety outcomes of the recently completed Phase IIb clinical trial with 0.5% PRO 2000 gel, and predict that tenofovir gel will not adversely affect the genital tract.
A randomized controlled trial of pegylated interferon-α2a plus adefovir dipivoxil for hepatitis B e antigen-negative chronic hepatitis B
Authors: Piccolo Paola , Lenci Ilaria , Demelia Luigi , Bandiera Franco , Piras Maria R , Antonucci Giorgio , Nosotti Lorenzo , Mari Terenzio , De Santis Adriano , Ponti Maria L , Sorbello Orazio , Iacomi Fabio , Angelico Mario 
Published: December 2009

Background Pegylated interferon (PEG-IFN)-α monotherapy is the current standard of care for short-term antiviral treatment of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). We aimed to assess the safety and efficacy of PEG-IFN-α plus adefovir dipivoxil (ADV) versus PEG-IFN-α monotherapy for compensated HBeAg-negative CHB. Methods A multicentre randomized controlled trial was performed in eight outpatient hepatology/infectious disease clinics in central Italy. A total of 60 patients (67% male and median age 48 years) with biopsy-proven HBeAg-negative compensated CHB (mean alanine aminotranferase [ALT] levels 3.3 ±3x the upper normal limit and serum hepatitis B virus [HBV] DNA 5.8 ±0.9 log10 IU/ml) were randomized at baseline to receive PEG-IFN-α2a 180 μg/week plus ADV 10 mg/day or PEG-IFN-α2a monotherapy for 48 weeks. Post-treatment follow-up was for 24 additional weeks. The primary end point was sustained HBV DNA suppression defined as serum HBV DNA<2,000 IU/ml after 24 weeks of post-treatment follow-up. The secondary end point was ALT normalization at the end of follow-up. Results At week 48, HBV DNA was undetectable in 20/30 (67%) in the combination group versus 11/30 (37%) patients in the monotherapy group ( P=0.02). ALT normalization was achieved in 17/30 (57%) versus 10/30 (30%) patients, respectively ( P=0.03). At week 72, sustained virological response was achieved in 7/30 (23.3%) in the combination group versus 6/30 (20%) patients in the monotherapy group ( P=0.75); 5 (16%) patients in each group dropped out because of adverse events or non-compliance. Conclusions In HBeAg-negative CHB, combination PEG-IFN-α2a plus ADV for 48 weeks is safe and resulted in greater on-treatment efficacy than PEG-IFN-α2a monotherapy. No difference in sustained virological and biochemical response rates were observed between the two treatment regimens.
Non-Steroidal Anti-Inflammatory Drugs Increase the Antiretroviral Activity of Nucleoside Reverse Transcriptase Inhibitors in HIV Type-1-Infected T-Lymphocytes: Role of Multidrug Resistance Protein 4
Authors: Clemente Ma Isabel , Álvarez Susana , Serramía Ma Jesús , Turriziani Ombretta , Genebat Miguel , Leal Manuel , Fresno Manuel , Muñoz-Fernández Ma Ángeles 
Published: December 2009

Background The multidrug resistance proteins (MRPs) form a subfamily within the ATP binding cassette transporters that confer resistance to a variety of structurally unrelated compounds. MRP4 has been reported to transport antiretroviral drugs out of cells in an active process. Although the main therapeutic effects of non-steroidal anti-inflammatory drugs (NSAIDs) are their ability to inhibit cyclooxygenase activity, in recent years, some pharmacological effects independent of this action have been described, such as inhibition of the activity of MRP4. Methods Detection of MRP4 expression was carried out by Western blot analysis, immunofluorescence and flow cytometry in peripheral blood lymphocytes (PBLs). Cells were infected with HIV type-1NL4.3 isolate, and treated with anti-retroviral drugs plus different NSAIDs. Agp24 was measured by ELISA 3 days post-infection. Intracellular [3H] zidovudine (AZT) was quantified by a scintiller counter. Expression of different cell markers was assessed by flow cytometry. Results NSAIDs, as well as probenecid, were able to potentiate the antiretroviral effect of several nucleoside reverse transcriptase inhibitors (NRTIs). PBLs expressed MRP4 and treatment with ibuprofen did not affect this expression. However, MRP4 expression increased following phytohaemaglutinin and AZT treatment. This decrease of Agp24 was correlated with an increase in the intracellular AZT concentration. This effect was unrelated to changes on expression of CD4, CXCR4, cell viability or activation. Interestingly, patients treated with highly active antiretroviral therapy, who had a detectable viral load, presented a higher expression of MRP4 than those with an undetectable viral load. Conclusions NSAIDs can improve the antiretroviral activity of NRTIs, increasing their intracellular concentration by blocking MRP4. This finding could have implications for success of antiviral therapy.
Combined prophylactic and therapeutic intranasal vaccination against human papillomavirus type-16 using different adeno-associated virus serotype vectors
Authors: Nieto Karen , Kern Andrea , Leuchs Barbara , Gissmann Lutz , Müller Martin , Kleinschmidt Jürgen A 
Published: December 2009

Background Cervical cancer is the second most frequent cancer among woman worldwide and is considered to be caused by infection with high-risk papilloma viruses. Genetic immunization using recombinant adeno-associated virus (rAAV) vectors has shown great promise for vaccination against human papillomavirus (HPV) infections. Methods rAAV5, -8 and -9 vectors expressing an HPV16 L1/E7 fusion gene were generated and applied intranasally for combined prophylactic and therapeutic vaccination of mice. Results The rAAV5 and the rAAV9 vectors showed efficient induction of both humoral and cellular immune responses, whereas rAAV8 failed to immunize mice by the intranasal route. The L1-specific immune response evoked by expression of the L1/E7 fusion gene, however, was lower than that evoked by expression of the L1 antigen alone. This deficiency could be compensated by application of Escherichia coli heat-labile enterotoxin or monophsphoryl lipid as adjuvant upon vaccination with rAAV5-L1/E7. Coimmunization of rAAV9-L1/E7 with rAAV5-L1 or boosting of rAAV9-L1/E7 with rAAV5-L1 strongly increased L1-specific neutralizing antibody titres to levels above those achieved by vaccination with vectors expressing L1 alone. Both vectors elicited a vibrant cytotoxic T-lymphocyte response against L1 or E7. Nasal immunization with rAAV5 or rAAV9 was superior to vaccination with HPV16-L1 virus-like particles (VLPs) or HPV16-L1/E7 CVLPs with respect to humoral and cellular immune responses. Vaccination with the rAAV vectors led to a significant protection of animals against a challenge with different HPV tumour cell lines. Conclusions Our results show that rAAV5 and rAAV9 vectors are promising candidates for a non-invasive nasal vaccination strategy.
Preparation of Proteins and Peptides for Mass Spectrometry Analysis in a Bottom‐Up Proteomics Workflow
Authors: Gundry Rebekah L. , White Melanie Y. , Murray Christopher I. , Kane Lesley A. , Fu Qin , Stanley Brian A. , Van Eyk Jennifer E. 
Published: December 2009

AbstractThis unit outlines the steps required to prepare a sample for MS analysis following protein separation or enrichment by gel electrophoresis, liquid chromatography, and affinity capture within the context of a bottom‐up proteomics workflow in which the protein is first broken up into peptides, either by chemical or enzymatic digestion, prior to MS analysis. Also included are protocols for enrichment at the peptide level, including phosphopeptide enrichment and reversed‐phase chromatography for sample purification immediately prior to MS analysis. Finally, there is a discussion regarding the types of MS technologies commonly used to analyze proteomics samples, as well as important parameters that should be considered when analyzing the MS data to ensure stringent and robust protein identifications and characterization. Curr. Protoc. Mol. Biol. 88:10.25.1‐10.25.23. © 2009 by John Wiley & Sons, Inc.
In Vitro Selection of RNA Aptamers to a Protein Target by Filter Immobilization
Authors: Hall Bradley , Arshad Seyed , Seo Kyunghyun , Bowman Catherine , Corley Meredith , Jhaveri Sulay D. , Ellington Andrew D. 
Published: December 2009

AbstractThis unit describes the selection of aptamers from a pool of single‐stranded RNA by binding to a protein target. Aptamers generated from this selection experiment can potentially act as protein function inhibitors, and may find applications as therapeutic or diagnostic reagents. A pool of dsDNA is used to generate an ssRNA pool, which is mixed with the protein target. Bound complexes are separated from unbound reagents by filtration, and the RNA:protein complexes are amplified by a combination of reverse transcription, PCR, and in vitro transcription.Curr. Protoc. Mol. Biol. 88:24.3.1‐24.3.27. © 2009 by John Wiley & Sons, Inc.
Evaluation of the Mitochondrial Respiratory Chain and Oxidative Phosphorylation System Using Blue Native Gel Electrophoresis
Authors: Díaz Francisca , Barrientos Antoni , Fontanesi Flavia 
Published: December 2009

AbstractThe oxidative phosphorylation (OXPHOS) system consists of five multimeric complexes embedded in the mitochondrial inner membrane. They work in concert to drive the aerobic synthesis of ATP. Mitochondrial and nuclear DNA mutations affecting the accumulation and function of these enzymes are the most common cause of mitochondrial diseases and have also been associated with neurodegeneration and aging. For this reason, several approaches for the assessment of the OXPHOS system enzymes have been progressively developed. Based on methods described elsewhere, the use of blue native gel electrophoresis (BNGE) techniques to routinely assess the OXPHOS system and screen for enzymatic defects in homogenates or mitochondrial preparations from tissues or cultured cells is described here. Curr. Protoc. Hum. Genet. 63:19.4.1‐19.4.12. © 2009 by John Wiley & Sons, Inc.
Measurement of Molecular Mobility with Fluorescence Correlation Spectroscopy
Authors: Vámosi György , Damjanovich Sándor , Szöllősi János , Vereb György 
Published: December 2009

AbstractFluorescence correlation spectroscopy (FCS) is a fluctuation method established three decades ago, whose application to cellular systems became popular in the last decade. Fluctuations of fluorescence emission are observed from a small, femtoliter to sub‐femtoliter, usually confocal volume at high time resolution. A time‐dependent autocorrelation function is generated and evaluated to obtain time constants of photophysical and photochemical reactions, as well as of molecular diffusion and in the observation volume. Molecules in various subcellular compartments—including the nucleus, the cytoplasm, and the membrane—can be observed after labeling them with antibodies, ligands, or fluorescent proteins. The anomaly of diffusion, the local concentration, and the average fluorescence per diffusing particle can also be determined, all of which can be characteristic of molecular interactions. A two‐color version of FCS, fluorescence cross‐correlation spectroscopy, can also be applied to observe co‐diffusion, i.e., stable association of two distinct molecular species in their cellular environment. Curr. Protoc. Cytom. 50:2.15.1‐2.15.19. © 2009 by John Wiley & Sons, Inc.
Total Internal Reflection Fluorescence (TIRF) Microscopy
Authors: Fish Kenneth N. 
Published: December 2009

AbstractTotal internal reflection fluorescence (TIRF) microscopy (TIRFM) is an elegant optical technique that provides for the excitation of fluorophores in an extremely thin axial region (“optical section”). The method is based on the principle that when excitation light is totally internally reflected in a transparent solid (e.g., coverglass) at its interface with liquid, an electromagnetic field, called the evanescent wave, is generated in the liquid at the solid‐liquid interface and is the same frequency as the excitation light. Since the intensity of the evanescent wave exponentially decays with distance from the surface of the solid, only fluorescent molecules within a few hundred nanometers of the solid are efficiently excited. This unit will briefly review the history, optical theory, and different hardware configurations used in TIRFM. In addition, it will provide experimental details and methodological considerations for studying receptors at the plasma membrane in neurons. Curr. Protoc. Cytom. 50:12.18.1‐12.18.13. © 2009 by John Wiley & Sons, Inc.
Signals, Information and Knowledge, and Meaning
Authors: Yang Qing Ping 
Published: December 2009

Abstract
As the purpose of measurement is acquisition of information and knowledge about the observed system, measurement may be viewed as part of a human cognition process. It involves both human and machine perceptions through direct and indirect experiences. This article examines basic elements and processes of measurement, that is, signal, data, information, and knowledge. It further discusses relevant cognitive issues, and relationships between human and machine perceptions and between direct and indirect experiences.
Nature and Scope of Closed‐loop Systems
Authors: Sydenham Peter H. 
Published: December 2009

AbstractMeasuring sensors are important in the formation of closed‐loop control applications; they often use feedback in their own internal operation. Control engineering techniques are also used to improve the response time of actuators and sensors. Whereas most of modern control is implemented in the digital signal domain the underlying principles and methods used are still those originally developed for analog signal systems. This article deals with a brief history of feedback control; an intuitive study of a controller; how a mathematical model is developed for a closed‐loop system; how some common control systems limitation are handled; and the nature of closed‐loop setups in measuring systems.
Principles of Epistemology as Related to Measurement
Authors: Ferris Timothy Lindsay John 
Published: December 2009

Abstract
Epistemology is the branch of philosophy that is devoted to the study of the nature of knowing and knowledge. Concerns of epistemology include how it is possible to know anything, and to have certainty that what one apprehends is as it appears to be. Epistemology differs from ontology in that ontology concerns understanding what things are rather than how they are experienced and known. Epistemology is relevant to the study of measurement because measurement is the process of gaining knowledge of some aspect of things or phenomena through application of appropriate instruments.