bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genesis of the characteristic pulmonary venous pressure waveform as described by the reservoir‐wave model
Authors: Bouwmeester J. Christopher , Belenkie Israel , Shrive Nigel G. , Tyberg John V. 
Published: July 2014

Key points
In pressure flow data from a pulmonary vein, we use the reservoir wave model to separate the effects of an elastic venous reservoir from the effects of waves created by the heart.
Wave intensity analysis was used to separate the effects of waves generated upstream by the right ventricle from the effects of waves generated downstream by the left atrium and left ventricle.
Most waves are created by the left atrium and left ventricle and can be linked to events that occur during the cardiac cycle.
Waves transmitted through the pulmonary circulation are attenuated less when blood volume is increased but are attenuated more and delayed when the lungs are expanded.
The drainage of pulmonary arterial and venous reservoirs are responsible for substantial changes in measured pulmonary venous pressure and flow but waves are associated with the conventional landmarks of these characteristic waveforms.
AbstractConventional haemodynamic analysis of pulmonary venous and left atrial (LA) pressure waveforms yields substantial forward and backward waves throughout the cardiac cycle; the reservoir wave model provides an alternative analysis with minimal waves during diastole. Pressure and flow in a single pulmonary vein (PV) and the main pulmonary artery (PA) were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading, and positive‐end expiratory pressure (PEEP) were observed. The reservoir wave model was used to determine the reservoir contribution to PV pressure and flow. Subtracting reservoir pressure and flow resulted in ‘excess’ quantities which were treated as wave‐related. Wave intensity analysis of excess pressure and flow quantified the contributions of waves originating upstream (from the PA) and downstream (from the LA and/or left ventricle (LV)). Major features of the characteristic PV waveform are caused by sequential LA and LV contraction and relaxation creating backward compression (i.e. pressure‐increasing) waves followed by decompression (i.e. pressure‐decreasing) waves. Mitral valve opening is linked to a backwards decompression wave (i.e. diastolic suction). During late systole and early diastole, forward waves originating in the PA are significant. These waves were attenuated less with volume loading and delayed with PEEP. The reservoir wave model shows that the forward and backward waves are negligible during LV diastasis and that the changes in pressure and flow can be accounted for by the discharge of upstream reservoirs. In sharp contrast, conventional analysis posits forward and backward waves such that much of the energy of the forward wave is opposed by the backward wave.
Assembly of AMPA receptors: mechanisms and regulation
Authors: Gan Quan , Salussolia Catherine L. , Wollmuth Lonnie P. 
Published: July 2014

AbstractAMPA receptors (AMPARs) play a critical role in excitatory glutamatergic neurotransmission. The number and subunit composition of AMPARs at synapses determines the dynamics of fast glutamatergic signalling. Functional AMPARs on the cell surface are tetramers. Thus tetrameric assembly of AMPARs represents a promising target for modulating AMPAR‐mediated signalling in health and disease. Multiple structural domains within the receptor influence AMPAR assembly. In a proposed model for AMPAR assembly, the amino‐terminal domain underlies the formation of a dimer pool. The transmembrane domain facilitates the formation and enhances the stability of the tetramer. The ligand‐binding domain influences assembly through a process referred to as ‘domain swapping’. We propose that this core AMPAR assembly process could be regulated by neuronal signals and speculate on possible mechanisms for such regulation.
Osmotic activation of phospholipase C triggers structural adaptation in osmosensitive rat supraoptic neurons
Authors: Shah Love , Bansal Vimal , Rye Peter L. , Mumtaz Naima , Taherian Amir , Fisher Thomas E. 
Published: July 2014

Key points
Acutely isolated rat magnocellular neurosecretory cells (MNCs) display reversible hypertrophy when exposed to hypertonic saline (325 mosmol kg−1) for tens of minutes.
Osmotically evoked hypertrophy is prevented by agents that block Na+ channels, TRPV1 channels (which mediate an osmotically evoked depolarization in these cells), L‐type Ca2+ channels, and exocytotic fusion and is associated with an increase in whole‐cell capacitance.
Exposure to hypertonic saline activates phospholipase C leading to a decrease in plasma membrane phosphatidylinositol 4,5‐bisphosphate.
Inhibition of phospholipase C or protein kinase C prevents osmotically evoked hypertrophy and activation of protein kinase C evokes hypertrophy in the absence of an increase in osmolality.
These results suggest that osmotically evoked hypertrophy is triggered by an increase in MNC action potential firing, leading to Ca2+ influx, the activation of phospholipase C, an increase in diacylglycerol, and the activation of protein kinase C.
AbstractThe magnocellular neurosecretory cells of the hypothalamus (MNCs) synthesize and secrete vasopressin or oxytocin. A stretch‐inactivated cation current mediated by TRPV1 channels rapidly transduces increases in external osmolality into a depolarization of the MNCs leading to an increase in action potential firing and thus hormone release. Prolonged increases in external osmolality, however, trigger a reversible structural and functional adaptation that may enable the MNCs to sustain high levels of hormone release. One poorly understood aspect of this adaptation is somatic hypertrophy. We demonstrate that hypertrophy can be evoked in acutely isolated rat MNCs by exposure to hypertonic solutions lasting tens of minutes. Osmotically evoked hypertrophy requires activation of the stretch‐inactivated cation channel, action potential firing, and the influx of Ca2+. Hypertrophy is prevented by pretreatment with a cell‐permeant inhibitor of exocytotic fusion and is associated with an increase in total membrane capacitance. Recovery is disrupted by an inhibitor of dynamin function, suggesting that it requires endocytosis. We also demonstrate that hypertonic solutions cause a decrease in phosphatidylinositol 4,5‐bisphosphate in the plasma membranes of MNCs that is prevented by an inhibitor of phospholipase C (PLC). Inhibitors of PLC or protein kinase C (PKC) prevent osmotically evoked hypertrophy, and treatment with a PKC‐activating phorbol ester can elicit hypertrophy in the absence of changes in osmolality. These studies suggest that increases in osmolality cause fusion of internal membranes with the plasma membrane of the MNCs and that this process is mediated by activity‐dependent activation of PLC and PKC.
The contributions of filaments and cross‐bridges to sarcomere compliance in skeletal muscle
Authors: Brunello Elisabetta , Caremani Marco , Melli Luca , Linari Marco , Fernandez‐Martinez Manuel , Narayanan Theyencheri , Irving Malcolm , Piazzesi Gabriella , Lombardi Vincenzo , Reconditi Massimo 
Published: July 2014

Key points
Muscle contraction is driven at the molecular level by a structural working stroke in the head domain of the myosin cross‐bridge linking the thick and thin filaments. Crystallographic models suggest that the working stroke corresponds to a relative movement of 11 nm between the attachments of the head domain to the thin and thick filaments.
The molecular mechanism of force generation depends on the relationship between cross‐bridge force and movement, which is determined by cross‐bridge and filament compliances.
Here we measured the compliance of the cross‐bridges and of the thin and thick filaments by combining mechanical and X‐ray diffraction experiments.
The results show that cross‐bridge compliance is relatively low and fully accounted for by the elasticity of the myosin head, suggesting that the myosin cross‐bridge generates isometric force by a small sub‐step of the 11 nm stroke that drives filament sliding at low load.
AbstractForce generation in the muscle sarcomere is driven by the head domain of the myosin molecule extending from the thick filament to form cross‐bridges with the actin‐containing thin filament. Following attachment, a structural working stroke in the head pulls the thin filament towards the centre of the sarcomere, producing, under unloaded conditions, a filament sliding of ∼11 nm. The mechanism of force generation by the myosin head depends on the relationship between cross‐bridge force and movement, which is determined by compliances of the cross‐bridge (Ccb) and filaments. By measuring the force dependence of the spacing of the high‐order myosin‐ and actin‐based X‐ray reflections from sartorius muscles of Rana esculenta we find a combined filament compliance (Cf) of 13.1 ± 1.2 nm MPa−1, close to recent estimates from single fibre mechanics (12.8 ± 0.5 nm MPa−1). Ccb calculated using these estimates is 0.37 ± 0.12 nm pN−1, a value fully accounted for by the compliance of the myosin head domain, 0.38 ± 0.06 nm pN−1, obtained from the intensity changes of the 14.5 nm myosin‐based X‐ray reflection in response to 3 kHz oscillations imposed on single muscle fibres in rigor. Thus, a significant contribution to Ccb from the myosin tail that joins the head to the thick filament is excluded. The low Ccb value indicates that the myosin head generates isometric force by a small sub‐step of the 11 nm stroke that drives filament sliding at low load. The implications of these results for the mechanism of force generation by myosins have general relevance for cardiac and non‐muscle myosins as well as for skeletal muscle.
Improving mass candidate detection in mammograms via feature maxima propagation and local feature selection
Authors: Melendez Jaime , Sánchez Clara I. , van Ginneken Bram , Karssemeijer Nico 
Published: July 2014

Purpose:Mass candidate detection is a crucial component of multistep computer‐aided detection (CAD) systems. It is usually performed by combining several local features by means of a classifier. When these features are processed on a per‐image‐location basis (e.g., for each pixel), mismatching problems may arise while constructing feature vectors for classification, which is especially true when the behavior expected from the evaluated features is a peaked response due to the presence of a mass. In this study, two of these problems, consisting of maxima misalignment and differences of maxima spread, are identified and two solutions are proposed.Methods:The first proposed method, feature maxima propagation, reproduces feature maxima through their neighboring locations. The second method, local feature selection, combines different subsets of features for different feature vectors associated with image locations. Both methods are applied independently and together.Results:The proposed methods are included in a mammogram‐based CAD system intended for mass detection in screening. Experiments are carried out with a database of 382 digital cases. Sensitivity is assessed at two sets of operating points. The first one is the interval of 3.5–15 false positives per image (FPs/image), which is typical for mass candidate detection. The second one is 1 FP/image, which allows to estimate the quality of the mass candidate detector's output for use in subsequent steps of the CAD system. The best results are obtained when the proposed methods are applied together. In that case, the mean sensitivity in the interval of 3.5–15 FPs/image significantly increases from 0.926 to 0.958 (p < 0.0002). At the lower rate of 1 FP/image, the mean sensitivity improves from 0.628 to 0.734 (p < 0.0002).Conclusions:Given the improved detection performance, the authors believe that the strategies proposed in this paper can render mass candidate detection approaches based on image location classification more robust to feature discrepancies and prove advantageous not only at the candidate detection level, but also at subsequent steps of a CAD system.
SU‐E‐T‐412: Effect of Ingested Contrast Media On Dose Reporting for GI Malignancies Comparing Multiple Dose Calculation Algorithms
Authors: Doemer A , Miller B , Chetty I 
Published: July 2014

Purpose:Varian AcurosXB calculates dose‐to‐medium (Dm) as well as the clinically prevalent dose‐to‐water (Dw). For abdominal malignancies, ingested contrast is used during simulation to delineate the treatment volume (TV) or outline the organ at risk (OAR), but this effect is transient. The purpose of this study is to evaluate the effect of contrast media on dose reporting using AAA, Acuros(Dw) and Acuros(Dm).Methods:Ingested contrast was contoured and either “forced” to water density or left uncorrected. Six plans were generated for 26 patients in Eclipse using identical leaf motions and MU values. The Acuros(Dm) forced density plan was our gold standard.Results:For 6MV plans where contrast was in the TV, AAA underrepresented the dose to the contrast region by 3.91%±3.08% (p=0.037) and 2.51%±1.25% (p=0.005) for unforced and forced densities respectively. Acuros(Dw) plans with unforced and forced densities overrepresented the dose by 2.97%±1.23% (p=.001) and 1.66%±0.24% (p=2.5e‐4). For 6MV plans where contrast was an OAR, all plans were not statistically significantly different from the Acuros(dm) plan. For 15MV plans where contrast was in the TV, AAA overrepresented the dose to the contrast region by 0.73%±0.49% (p=0.015) and 0.95%±0.39% (p=0.002) for unforced and forced densities respectively. Acuros(Dw) plans with unforced and forced densities overrepresented the dose by 2.15%±1.20% (p=0.009) and 1.00%±0.63% (p=0.007). Plans calculated with an unforced density in Acuros dm consistently showed the closest agreement to the Acuros(Dm) plan calculated with forced densities. For all 26 plans, the difference was ‐0.25%±0.84%.Conclusion:The appearance of contrast media will impact dose calculation. More clinical studies are needed to determine if dw and dm reporting shows any clinical significance. Care should be taken to force the density of contrast media in the GI region to a suitable value. As a fail safe condition, the use of Acuros(Dm) is recommended for these treatments.
SU‐E‐T‐413: Experience‐Based VMAT Plan Quality Database
Authors: Bernstein K , Kalach N , Wolthuis B , Tai C , Kravchuk A , Bernstein E 
Published: July 2014

Purpose:To quantify VMAT plan quality using a retrospective study of over 200 clinical treated VMAT plans created using the Eclipse Treatment Planning System to create benchmarks of plan quality for a few categories of treatment sites.Methods:Using a controlled phantom geometry, various dosimetric indices were investigated to quantify dosimetric plan quality as a function of isocenter displacement from center of mass, average path length, number of arcs and PTV proximity to critical structures. Beginning with published dosimetry indices from SRS and SBRT evaluations, UDI (Unified Dosimetry Index) and modified UDI were tested before creating a new factor VMAT‐DI. VMAT‐DI was developed within boundaries of this project and it includes renormalized factors of conformity index, coverage index, modified gradient index and homogeneity index as well as indices based on routine clinical practice such as absolute dose max index. The plans were then evaluated using the VMAT‐DI such that benchmarks for planning could be created.Results:The majority of the plans evaluated could be assigned VMAT‐DI values within a range for each treatment site. However, the outliers were results of difficult planning parameters such as very irregular targets, inhomogeneities or difficult to achieve critical structure constraints. To effectively use VMAT‐DI for guidance, especially for prediction of the plan quality for body sites new to the practice, VMATDI database needs to be subdivided by target complexity and by body site index/average path length factor.Conclusion:An experienced‐based VMAT‐DI database can be used to help analyze plans before evaluation by the physician to show that it adheres to the clinical standards of previously treated VMAT plans which will make a guideline for concluding the optimization. The introduction of institution‐wide clinical planning protocols, standardizing OAR naming and constraints will make it possible to incorporate a cumulative critical structure dosimetry index such as NTCP.
SU‐E‐T‐414: TG‐129 Implementation On BrachyvisionTM
Authors: Nguyen A , Hu Y , He R , Paul T , Plowman A , Mobit P , Ma J , Packianathan S , Kanakamedala M , Yang C 
Published: July 2014

Purpose:To outline the steps taken to clinically implement TG‐129 on Brachyvision™ Treatment Planning System and to show the dosimetric differences that can be expected from the original COMS Eye Plaque model.Methods:The original COMS‐Eye Plaque protocol was based on the following simplification: point source model in infinite water medium, 1D geometric function, 1D radial dose function and no anisotropy. Recently, AAPM Task Group 129 had made two specific recommendations: 1> Upgrade to TG‐43U1 line source model; and 2> Report the heterogeneity corrected dose. Upgrading to line TG‐43U1 line source model was done by a creating a seed collection in Brachyvision (version 11) for each plaque size. For each seed in the collection, both end coordinates had to be entered into the software. Full line source model was followed to compute the homogeneous dose at the prescription point. This homogeneous dose was converted to heterogeneous dose using a conversion table. Dose to prescription points for five different plaque sizes, including one customized notched plaque, was calculated using the implemented TG‐129 model and compared against actual COMS derived doses from previously treated patient plans. Conversion to heterogeneous doses was done based on table 2 of TG‐129 report.Results:As expected, dose difference between COMS and TG‐129 was relatively minor, ranging from ‐0.15% to 1.91% at the prescription point. On the other hand, heterogeneous dose, which should be used for reporting purpose only, can be up to ∼17% lower than the corresponding homogeneous dose.Conclusion:Conversion to TG‐129 can be rapidly accomplished in 1–2 weeks. The initial time investment can be quickly recouped since the TPS plans created can be modified for different patient cases. Dosimetric difference between TG‐129 and the original COMS model is small, generally less than 2%.
SU‐E‐T‐415: An Ionization Chamber Array with High Spatial Resolution for External Beam Radiotherapy
Authors: Togno M , Wilkens J , Menichelli D 
Published: July 2014

Purpose:To characterize an ionization chamber array technology with high spatial resolution and high charge collection efficiency for external beam radiotherapy.Methods:The prototype under test is a linear array of air vented ionization chambers developed by IBA Dosimetry, consisting of 80 pixels with 3.5mm spatial resolution and 4mm3 sensitive volume. The detector was characterized in a plastic phantom with 6 0 Co radiation and MV X‐rays from an ELEKTA Agility LINAC (with flattened and unflattened beam qualities). Bias voltage was varied in order to evaluate charge collection efficiency. A commercial array of ionization chambers (MatriXX Evolution, IBA Dosimetry) and an amorphous silicon flat panel in direct conversion configuration were used as references.Results:Repeatability (0.4%) and stability under continuous gamma irradiation (0.3%) are very good, in spite of low active volume and sensitivity (∼200pC/Gy). Charge collection efficiency is higher than 99% already at 150V with ∼2mGy dose per pulse, leading to a ±1.1% sensitivity change with dose per pulse in the range 0.09‐2mGy (covering all flattened and unflattened applications). Measured dose profiles are in agreement with MatriXX for fields larger than 2×2cm2, in which case the linear array offers a much better characterization of the penumbra region. Down to 1×1cm2, measured profiles are in very good agreement with the flat panel.Conclusion:The array represents a valuable tool for the characterization of treatment fields in which high spatial resolution is required, together with the dosimetric performance of air vented ionization chambers. Such a technology would be particularly valuable in association with advanced treatment modalities such as rotational radiotherapy, stereotactic treatments (even with unflattened beam qualities) and proton therapy, due to the insensitivity of the chambers on dose per pulse. In the future, a two dimensional prototype based on this technology will be developed and tested.This research project has been supported by a Marie Curie Early Initial Training Network Fellowship of the European Community's Seventh Framework Programme under contract number (PITN‐GA‐2011‐289198‐
SU‐E‐T‐416: VMAT Dose Calculations Using Cone Beam CT Images: A Preliminary Study
Authors: Yu S , Sehgal V , kuo J , Daroui P , Ramsinghani N , Al‐Ghazi M 
Published: July 2014

Purpose:Cone beam CT (CBCT) images have been used routinely for patient positioning throughout the treatment course. However, use of CBCT for dose calculation is still investigational. The purpose of this study is to assess the utility of CBCT images for Volumetric Modulated Arc Therapy (VMAT) plan dose calculation.Methods:A CATPHAN 504 phantom (The Phantom Laboratory, Salem, NY) was used to compare the dosimetric and geometric accuracy between conventional CT and CBCT (in both full and half fan modes). Hounsfield units (HU) profiles at different density areas were evaluated. A C shape target that surrounds a central avoidance structure was created and a VMAT plan was generated on the CT images and copied to the CBCT phantom images. Patient studies included three brain patients, and one head and neck (H' N) patient. VMAT plans generated on the patients treatment planning CT was applied to CBCT images obtained during the first treatment. Isodose distributions and dosevolume‐ histograms (DVHs) were compared.Results:For the phantom study, the HU difference between CT and CBCT is within 100 (maximum 96 HU for Teflon CBCT images in full fan mode). The impact of these differences on the calculated dose distributions was clinically insignificant. In both phantom and patient studies, target DVHs based on CBCT images were in excellent agreement with those based on planning CT images. Mean, Median, near minimum (D98%), and near maximum (D2%) doses agreed within 0‐2.5%. A slightly larger discrepancy is observed in the patient studies compared to that seen in the phantom study, (0‐1% vs. 0 – 2.5%).Conclusion:CBCT images can be used to accurately predict dosimetric results, without any HU correction. It is feasible to use CBCT to evaluate the actual dose delivered at each fraction. The dosimetric consequences resulting from tumor response and patient geometry changes could be monitored.