368 research outputs found
Inaugural Review Prize 2023: The exercise hyperpnoea dilemma:A 21stâcentury perspective
During mild or moderate exercise, alveolar ventilation increases in direct proportion to metabolic rate, regulating arterial CO2 pressure near resting levels. Mechanisms giving rise to the hyperpnoea of exercise are unsettled despite over a century of investigation. In the past three decades, neuroscience has advanced tremendously, raising optimism that the âexercise hyperpnoea dilemmaâ can finally be solved. In this review, new perspectives are offered in the hope of stimulating original ideas based on modern neuroscience methods and current understanding. We first describe the ventilatory control system and the challenge exercise places upon bloodâgas regulation. We highlight relevant system properties, including feedforward, feedback and adaptive (i.e., plasticity) control of breathing. We then elaborate a seldom explored hypothesis that the exercise ventilatory response continuously adapts (learns and relearns) throughout life and ponder if the memory âengramâ encoding the feedforward exercise ventilatory stimulus could reside within the cerebellum. Our hypotheses are based on accumulating evidence supporting the cerebellum's role in motor learning and the numerous direct and indirect projections from deep cerebellar nuclei to brainstem respiratory neurons. We propose that cerebellar learning may be obligatory for the accurate and adjustable exercise hyperpnoea capable of tracking changes in life conditions/experiences, and that learning arises from specific cerebellar microcircuits that can be interrogated using powerful techniques such as optogenetics and chemogenetics. Although this review is speculative, we consider it essential to reframe our perspective if we are to solve the tillânow intractable exercise hyperpnoea dilemma
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Resonant Soft X-Ray Contrast Variation Methods as Composition-Specific Probes of Thin Polymer Film Structure
We have developed complementary soft x-ray scattering and reflectometry techniques that allow for the morphological analysis of thin polymer films without resorting to chemical modification or isotopic 2 labeling. With these techniques, we achieve significant, x-ray energy-dependent contrast between carbon atoms in different chemical environments using soft x-ray resonance at the carbon edge. Because carbon-containing samples absorb strongly in this region, the scattering length density depends on both the real and imaginary parts of the atomic scattering factors. Using a model polymer film of poly(styrene-b-methyl methacrylate), we show that the soft x-ray reflectivity data is much more sensitive to these atomic scattering factors than the soft x-ray scattering data. Nevertheless, fits to both types of data yield useful morphological details on the polymer?slamellar structure that are consistent with each other and with literature values
APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia
Rational
Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses.
Objectives
Identify individual factors (eg, genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH).
Methods
In 17 healthy individuals (age = 27 ± 5âyr), associations between individual factors and changes in the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential (MEP) amplitude and inspiratory mouth occlusion pressures (P0.1) were evaluated. Single nucleotide polymorphisms (SNPs) in genes linked with mechanisms of AIH induced phrenic motor plasticity (BDNF, HTR2A, TPH2, MAOA, NTRK2) and neuronal plasticity (apolipoprotein E, APOE) were tested. Variations in AIHH induced plasticity with age and sex were also analyzed. Additional experiments in humanized (h)ApoE knock-in rats were performed to test causality.
Results
AIHH-induced changes in diaphragm MEP amplitudes were lower in individuals heterozygous for APOE4 (i.e., APOE3/4) compared to individuals with other APOE genotypes (P = 0.048) and the other tested SNPs. Males exhibited a greater diaphragm MEP enhancement versus females, regardless of age (P = 0.004). Additionally, age was inversely related with change in P0.1 (P = 0.007). In hApoE4 knock-in rats, AIHH-induced phrenic motor plasticity was significantly lower than hApoE3 controls (P \u3c 0.05).
Conclusions
APOE4 genotype, sex, and age are important biological determinants of AIHH-induced respiratory motor plasticity in healthy adults.
Addition To Knowledge Base
AIH is a novel rehabilitation strategy to induce functional recovery of respiratory and non-respiratory motor systems in people with chronic spinal cord injury and/or neurodegenerative disease. Figure 5 Since most AIH trials report considerable inter-individual variability in AIH outcomes, we investigated factors that potentially undermine the response to an optimized AIH protocol, AIHH, in healthy humans. We demonstrate that genetics (particularly the lipid transporter, APOE), age and sex are important biological determinants of AIHH-induced respiratory motor plasticit
Follow-Up Near-infrared Spectroscopy of Ultraluminous Infrared Galaxies observed by ISO
We present low resolution near-infrared spectroscopy of an unbiased sample of
24 ultraluminous infrared galaxies (ULIRGs), selected from samples previously
observed spectroscopically in the mid-infrared with the Infrared Space
Observatory (ISO). Qualitatively, the near-infrared spectra resemble those of
starbursts. Only in one ULIRG, IRAS 04114-5117E, do we find spectroscopic
evidence for AGN activity. The spectroscopic classification in the
near-infrared is in very good agreement with the mid-infrared one. For a subset
of our sample for which extinction corrections can be derived from Pa-alpha and
Br-gamma, we find rather high Pa-alpha luminosities, in accordance with the
powering source of these galaxies being star formation.[Fe] emission is strong
in ULIRGs and may be linked to starburst and superwind activity. Additionally,
our sample includes two unusual objects. The first, IRAS F00183-7111, exhibits
extreme [Fe] emission and the second, IRAS F23578-5307, is according to our
knowledge one of the most luminous infrared galaxies in H2 rotation-vibration
emission.Comment: Accepted for publication in A&A (12 pages, 4 figures). See
http://www.mpia-hd.mpg.de/homes/dannerb/ for a version with higher quality
figure
Design of Experiments for Screening
The aim of this paper is to review methods of designing screening
experiments, ranging from designs originally developed for physical experiments
to those especially tailored to experiments on numerical models. The strengths
and weaknesses of the various designs for screening variables in numerical
models are discussed. First, classes of factorial designs for experiments to
estimate main effects and interactions through a linear statistical model are
described, specifically regular and nonregular fractional factorial designs,
supersaturated designs and systematic fractional replicate designs. Generic
issues of aliasing, bias and cancellation of factorial effects are discussed.
Second, group screening experiments are considered including factorial group
screening and sequential bifurcation. Third, random sampling plans are
discussed including Latin hypercube sampling and sampling plans to estimate
elementary effects. Fourth, a variety of modelling methods commonly employed
with screening designs are briefly described. Finally, a novel study
demonstrates six screening methods on two frequently-used exemplars, and their
performances are compared
Serum microrna biomarkers for detection of non-small cell lung cancer
Non small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality world-wide and the majority of cases are diagnosed at late stages of disease. There is currently no cost-effective screening test for NSCLC, and the development of such a test is a public health imperative. Recent studies have suggested that chest computed tomography screening of patients at high risk of lung cancer can increase survival from disease, however, the cost effectiveness of such screening has not been established. In this Phase I/II biomarker study we examined the feasibility of using serum miRNA as biomarkers of NSCLC using RT-qPCR to examine the expression of 180 miRNAs in sera from 30 treatment naive NSCLC patients and 20 healthy controls. Receiver operating characteristic curves (ROC) and area under the curve were used to identify differentially expressed miRNA pairs that could distinguish NSCLC from healthy controls. Selected miRNA candidates were further validated in sera from an additional 55 NSCLC patients and 75 healthy controls. Examination of miRNA expression levels in serum from a multi-institutional cohort of 50 subjects (30 NSCLC patients and 20 healthy controls) identified differentially expressed miRNAs. A combination of two differentially expressed miRNAs miR-15b and miR-27b, was able to discriminate NSCLC from healthy controls with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100% in the training set. Upon further testing on additional 130 subjects (55 NSCLC and 75 healthy controls), this miRNA pair predicted NSCLC with a specificity of 84% (95% CI 0.73-0.91), sensitivity of 100% (95% CI; 0.93-1.0), NPV of 100%, and PPV of 82%. These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of NSCLC. Further testing in a Phase III biomarker study in is necessary for validation of these results. © 2012 Hennessey et al
Earnings Functions and the Measurement of the Determinants of Wage Dispersion: Extending Oaxaca's Approach
Prototype ATLAS IBL Modules using the FE-I4A Front-End Readout Chip
The ATLAS Collaboration will upgrade its semiconductor pixel tracking
detector with a new Insertable B-layer (IBL) between the existing pixel
detector and the vacuum pipe of the Large Hadron Collider. The extreme
operating conditions at this location have necessitated the development of new
radiation hard pixel sensor technologies and a new front-end readout chip,
called the FE-I4. Planar pixel sensors and 3D pixel sensors have been
investigated to equip this new pixel layer, and prototype modules using the
FE-I4A have been fabricated and characterized using 120 GeV pions at the CERN
SPS and 4 GeV positrons at DESY, before and after module irradiation. Beam test
results are presented, including charge collection efficiency, tracking
efficiency and charge sharing.Comment: 45 pages, 30 figures, submitted to JINS
A New Empirical Approach to Explain the Stock Market Yield: A Combination of Dynamic Panel Estimation and Factor Analysis
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