The effect of string tension variation on the perceived pitch of a classical guitar

Actual motion of a vibrating guitar string is a superposition of many possible shapes (modes) in which it could vibrate. Each of these modes has a corresponding frequency, and the lowest frequency is associated with a shape idealised as a single wave, referred to as the fundamental mode. The other contributing modes, each with their own progressively higher frequency, are referred to as overtones, or harmonics. By attaching a string to a medium (a soundboard) capable of a response to the vibrating string, sound waves are generated. The sound heard is dominated by the fundamental mode, ‘coloured’ by contributions from the overtones, as explained by the classical theory of vibration. The classical theory, however, assumes that the string tension remains constant during vibration, and this cannot be strictly true; when considering just the fundamental mode, string tension will reach two maximum changes, as it oscillates up and down. These changes, occurring twice during the fundamental period match the frequency of the octave higher, 1st overtone. It is therefore plausible to think that the changing tension effect, through increased force on the bridge and, therefore, greater soundboard deflection, could be amplifying the colouring effect of (at least) the 1st overtone. In this paper, we examine the possible influence of string tension variation on tonal response of a classical guitar. We use a perturbation model based on the classical result for a string in general vibration in conjunction with a novel method of assessment of plucking force that incorporates the engineering concept of geometric stiffness, to assess the magnitude of the normal force exerted by the string on the bridge. The results of our model show that the effect of tension variation is significantly smaller than that due to the installed initial static tension, and affects predominantly the force contribution arising from the fundamental mode. We, therefore, conclude that string tension variation does not contribute significantly to tonal response

HLA Class I Binding Motifs Derived from Random Peptide Libraries Differ at the COOH Terminus from Those of Eluted Peptides

Recombinant HLA-A2, HLA-B8, or HLA-B53 heavy chain produced in Escherichia coli was combined with recombinant β2-microglobulin (β2m) and a pool of randomly synthesised nonamer peptides. This mixture was allowed to refold to form stable major histocompatability complex (MHC) class I complexes, which were then purified by gel filtration chromatography. The peptides bound to the MHC class I molecules were subsequently eluted and sequenced as a pool. Peptide binding motifs for these three MHC class I molecules were derived and compared with previously described motifs derived from analysis of naturally processed peptides eluted from the surface of cells. This comparison indicated that the peptides bound by the recombinant MHC class I molecules showed a similar motif to naturally processed and presented peptides, with the exception of the peptide COOH terminus. Whereas the motifs derived from naturally processed peptides eluted from HLA-A2 and HLA-B8 indicated a strong preference for hydrophobic amino acids at the COOH terminus, this preference was not observed in our studies. We propose that this difference reflects the effects of processing or transport on the peptide repertoire available for binding to MHC class I molecules in vivo

Extraction and inhibition of enzymatic activity of botulinum neurotoxins /B1, /B2, /B3, /B4, and /B5 by a panel of monoclonal anti-BoNT/B antibodies

<p>Abstract</p> <p>Background</p> <p>Botulism is caused by botulinum neurotoxins (BoNTs), extremely toxic proteins which can induce respiratory failure leading to long-term intensive care or death. Treatment for botulism includes administration of antitoxins, which must be administered early in the course of the intoxication; therefore, rapid determination of human exposure to BoNT is an important public health goal. In previous work, our laboratory reported on Endopep-MS, a mass spectrometry-based activity method for detecting and differentiating BoNT/A, /B, /E, and /F in clinical samples. We also demonstrated that antibody-capture is effective for purification and concentration of BoNTs from complex matrices such as clinical samples. However, some antibodies inhibit or neutralize the enzymatic activity of BoNT, so the choice of antibody for toxin extraction is critical.</p> <p>Results</p> <p>In this work, we evaluated 24 anti-BoNT/B monoclonal antibodies (mAbs) for their ability to inhibit the <it>in vitro </it>activity of BoNT/B1, /B2, /B3, /B4, and /B5 and to extract those toxins. Among the mAbs, there were significant differences in ability to extract BoNT/B subtypes and inhibitory effect on BoNT catalytic activity. Some of the mAbs tested enhanced the <it>in vitro </it>light chain activity of BoNT/B, suggesting that BoNT/B may undergo conformational change upon binding some mAbs.</p> <p>Conclusions</p> <p>In addition to determining <it>in vitro </it>inhibition abilities of a panel of mAbs against BoNT/B1-/B5, this work has determined B12.2 and 2B18.2 to be the best mAbs for sample preparation before Endopep-MS. These mAb characterizations also have the potential to assist with mechanistic studies of BoNT/B protection and treatment, which is important for studying alternative therapeutics for botulism.</p

Lateralized hippocampal oscillations underlie distinct aspects of human spatial memory and navigation

The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1–3-Hz “low theta” band increases when viewing subsequently remembered object–location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition

Imaging-based clusters in former smokers of the COPD cohort associate with clinical characteristics: the SubPopulations and intermediate outcome measures in COPD study (SPIROMICS)

Background: Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping. Methods: An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, emphysema percentage, functional small airway disease percentage, Jacobian (volume change), anisotropic deformation index (directional preference in volume change), and tissue fractions at inspiration and expiration. Results: We derived four distinct imaging-based clusters as possible phenotypes with the sizes of 100, 80, 141, and 85, respectively. Cluster 1 subjects were asymptomatic and showed relatively normal airway structure and lung function except airway wall thickening and moderate emphysema. Cluster 2 subjects populated with obese females showed an increase of tissue fraction at inspiration, minimal emphysema, and the lowest progression rate of emphysema. Cluster 3 subjects populated with older males showed small airway narrowing and a decreased tissue fraction at expiration, both indicating air-trapping. Cluster 4 subjects populated with lean males were likely to be severe COPD subjects showing the highest progression rate of emphysema. Conclusions: QCT imaging-based metrics for former smokers allow for the derivation of statistically stable clusters associated with unique clinical characteristics. This approach helps better categorization of COPD sub-populations; suggesting possible quantitative structural and functional phenotypes.NIH [U01-HL114494, R01-HL112986, S10-RR022421]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2017R1D1A1B03034157]; Korea Ministry of Environment (MOE) [RE201806039]; NIH/NHLBI [HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, HHSN268200900020C]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Positive health effects of the natural outdoor environment in typical populations in different regions in Europe (PHENOTYPE): a study programme protocol

Introduction Growing evidence suggests that close contact with nature brings benefits to human health and well-being, but the proposed mechanisms are still not well understood and the associations with health remain uncertain. The Positive Health Effects of the Natural Outdoor environment in Typical Populations in different regions in Europe (PHENOTYPE) project investigates the interconnections between natural outdoor environments and better human health and well-being. Aims and methods The PHENOTYPE project explores the proposed underlying mechanisms at work (stress reduction/restorative function, physical activity, social interaction, exposure to environmental hazards) and examines the associations with health outcomes for different population groups. It implements conventional and new innovative high-tech methods to characterise the natural environment in terms of quality and quantity. Preventive as well as therapeutic effects of contact with the natural environment are being covered. PHENOTYPE further addresses implications for land-use planning and green space management. The main innovative part of the study is the evaluation of possible short-term and long-term associations of green space and health and the possible underlying mechanisms in four different countries (each with quite a different type of green space and a different use), using the same methodology, in one research programme. This type of holistic approach has not been undertaken before. Furthermore there are technological innovations such as the use of remote sensing and smartphones in the assessment of green space. Conclusions The project will produce a more robust evidence base on links between exposure to natural outdoor environment and human health and well-being, in addition to a better integration of human health needs into land-use planning and green space management in rural as well as urban areas

Relations between hinterland and foreland shortening: Sevier orogeny, central North American Cordillera

This is the published version. Copyright 2000 American Geophysical Union. All Rights Reserved.The tectonic relations between foreland and hinterland deformation in noncollisional orogens are critical to understanding the overall development of orogens. The classic central Cordilleran foreland fold-and-thrust belt in the United States (Late Jurassic to early Tertiary Sevier belt) and the more internal zones to the west (central Nevada thrust belt) provide data critical to understanding the development of internal and external parts of orogens. The Garden Valley thrust system, part of the central Nevada thrust belt, crops out in south-central Nevada within a region generally considered to be the hinterland of the Jurassic to Eocene Sevier thrust belt. The thrust system consists of at least four principal thrust plates composed of strata as young as Pennsylvanian in age that are unconformably overlain by rocks as old as Oligocene, suggesting that contraction occurred between those times. New U/Pb dates on intrusions that postdate contraction, combined with new paleomagnetic data showing significant tilting of one area prior to intrusion, suggest that regionally these thrusts were active before ∼85–100 Ma. The thrust faults are characterized by long, relatively steeply dipping ramps and associated folds that are broad and open to close, upright and overturned. Although now fragmented by Cenozoic crustal extension, individual thrusts can be correlated from range to range for tens to hundreds of kilometers along strike. We correlate the structurally lowest thrust of the Garden Valley thrust system, the Golden Gate-Mount Irish thrust, southward with the Gass Peak thrust of southern Nevada. This correlation carries the following regional implications. At least some of the slip across Jurassic to mid-Cretaceous foreland thrusts in southern Nevada continues northward along the central Nevada thrust belt rather than northeastward into Utah. This continuation is consistent with age relations, which indicate that thrusts in the type Sevier belt in central Utah are synchronous with or younger than the youngest thrusts in southern Nevada. This in turn implies that geometrically similar Sevier belt thrusts in Utah must die out southward before they reach Nevada, that slip along the southern Nevada thrusts is partitioned between central Nevada and Utah thrusts, or that the Utah thrusts persist into southeastern Nevada but are located east of the longitude of the central Nevada thrust belt. As a result of overall cratonward migration of thrusting, the central Nevada thrust belt probably formed the Cordilleran foreland fold-thrust belt early in the shortening event but later lay in the hinterland of the Sevier fold-thrust belt of Idaho-Wyoming-Utah

Improving Salmonella vector with rec mutation to stabilize the DNA cargoes

<p>Abstract</p> <p>Background</p> <p><it>Salmonella </it>has been employed to deliver therapeutic molecules against cancer and infectious diseases. As the carrier for target gene(s), the cargo plasmid should be stable in the bacterial vector. Plasmid recombination has been reduced in <it>E. coli </it>by mutating several genes including the <it>recA</it>, <it>recE</it>, <it>recF </it>and <it>recJ</it>. However, to our knowledge, there have been no published studies of the effect of these or any other genes that play a role in plasmid recombination in <it>Salmonella enterica</it>.</p> <p>Results</p> <p>The effect of <it>recA</it>, <it>recF </it>and <it>recJ </it>deletions on DNA recombination was examined in three serotypes of <it>Salmonella enterica</it>. We found that (1) intraplasmid recombination between direct duplications was RecF-independent in Typhimurium and Paratyphi A, but could be significantly reduced in Typhi by a Δ<it>recA </it>or Δ<it>recF </it>mutation; (2) in all three <it>Salmonella </it>serotypes, both Δ<it>recA </it>and Δ<it>recF </it>mutations reduced intraplasmid recombination when a 1041 bp intervening sequence was present between the duplications; (3) Δ<it>recA </it>and Δ<it>recF </it>mutations resulted in lower frequencies of interplasmid recombination in Typhimurium and Paratyphi A, but not in Typhi; (4) in some cases, a Δ<it>recJ </it>mutation could reduce plasmid recombination but was less effective than Δ<it>recA </it>and Δ<it>recF </it>mutations. We also examined chromosome-related recombination. The frequencies of intrachromosomal recombination and plasmid integration into the chromosome were 2 and 3 logs lower than plasmid recombination frequencies in Rec⁺strains. A Δ<it>recA </it>mutation reduced both intrachromosomal recombination and plasmid integration frequencies.</p> <p>Conclusions</p> <p>The Δ<it>recA </it>and Δ<it>recF </it>mutations can reduce plasmid recombination frequencies in <it>Salmonella enterica</it>, but the effect can vary between serovars. This information will be useful for developing <it>Salmonella </it>delivery vectors able to stably maintain plasmid cargoes for vaccine development and gene therapy.</p