bluuebunny/crossref_metadata_2025_split huggingface dataset:
DEVELOPMENT AND EVALUATION OF A SYSTEM DYNAMICS MODEL FOR INVESTIGATING AGRICULTURALLY DRIVEN LAND TRANSFORMATION IN THE NORTH CENTRAL UNITED STATES
Authors: TURNER BENJAMIN L. , WUELLNER MELISSA , NICHOLS TIMOTHY , GATES ROGER , TEDESCHI LUIS O. , DUNN BARRY H. 
Published: February 2016

AbstractLand transformation from grassland to cropland in the Northern Great Plains (NGP) has become a growing concern among many stakeholders. A growing body of work has sought to determine the amount and rate of land use change with less emphasis on the systemic structures or feedback processes of land use decisions. This paper presents the development of a system dynamics simulation model to integrate ecological, economic, and social components influencing land use decisions, including cattle ranching, cropland production, rural communities, land quality, and public policies. Evaluation indicated that the model satisfactorily predicted historical land, agricultural commodity, and rural community data from the model structure. Reference modes for key variables, including the farmland area, were characterized by a bias correction of 0.999, root mean squared error of prediction of 0.053, R2 of 0.921, and concordance correlation coefficient of 0.0959. The model was robust under extreme and varying sensitivity tests, as well as adequately predicting land use under changing system context. The model's major contributions were the inclusion of decision‐making feedbacks from economic and social signals with connectivity to land quality and elasticity values that drive land transformation. Limitations include lack of spatial input and output capabilities useful for visual interfacing.
Effects of 4‐phenylbutyrate therapy in a preterm infant with cholestasis and liver fibrosis
Authors: Ito Shogo , Hayashi Hisamitsu , Sugiura Tokio , Ito Koichi , Ueda Hiroko , Togawa Takao , Endo Takeshi , Tanikawa Ken , Kage Masayoshi , Kusuhara Hiroyuki , Saitoh Shinji 
Published: February 2016

AbstractThe bile salt export pump is expressed at the canalicular membrane of hepatocytes and mediates biliary excretion of bile salts. 4‐Phenylbutyrate (4 PB), a drug used to treat ornithine transcarbamylase deficiency, has been found to increase the hepatocanalicular expression of bile salt export pump. The beneficial effects of 4‐phenylbutyrate therapy have been reported for patients with progressive familial intrahepatic cholestasis, an inherited autosomal recessive liver disease. This is the first study to show the therapeutic effect of 4 PB in a preterm infant with cholestasis and liver fibrosis. The preterm infant had severe cholestasis with jaundice and failure to thrive refractory to ursodeoxycholic acid. Histology indicated giant cell hepatitis, cholestasis, and severe fibrosis. Bile salt export pump immunostaining showed lower expression than in a control. Oral 4 PB was started at a daily dose of 200 mg/kg/day. After the start of 4 PB therapy, cholestasis improved.
Engineered Tug‐of‐War Between Kinesin and Dynein Controls Direction of Microtubule Based Transport In Vivo
Authors: Rezaul Karim , Gupta Dipika , Semenova Irina , Ikeda Kazuho , Kraikivski Pavel , Yu Ji , Cowan Ann , Zaliapin Ilya , Rodionov Vladimir 
Published: February 2016

AbstractBidirectional transport of membrane organelles along microtubules (MTs) is driven by plus‐end directed kinesins and minus‐end directed dynein bound to the same cargo. Activities of opposing MT motors produce bidirectional movement of membrane organelles and cytoplasmic particles along MT transport tracks. Directionality of MT‐based transport might be controlled by a protein complex that determines which motor type is active at any given moment of time, or determined by the outcome of a tug‐of‐war between MT motors dragging cargo organelles in opposite directions. However, evidence in support of each mechanisms of regulation is based mostly on the results of theoretical analyses or indirect experimental data. Here, we test whether the direction of movement of membrane organelles in vivo can be controlled by the tug‐of‐war between opposing MT motors alone, by attaching a large number of kinesin‐1 motors to organelles transported by dynein to minus‐ends of MTs. We find that recruitment of kinesin significantly reduces the length and velocity of minus‐end‐directed dynein‐dependent MT runs, leading to a reversal of the overall direction of dynein‐driven organelles in vivo. Therefore, in the absence of external regulators tug‐of‐war between opposing MT motors alone is sufficient to determine the directionality of MT transport in vivo.
Erythrophagocytosis by plasmacytoid dendritic cells and monocytes is enhanced during inflammation
Authors: Richards Amanda L. , Hendrickson Jeanne E. , Zimring James C. , Hudson Krystalyn E. 
Published: February 2016

BACKGROUNDGeneration of antibodies against red blood cell (RBC) antigens can be a clinically significant problem. The underlying mechanisms that regulate the production of RBC antibodies are only partially understood; however, factors such as inflammation significantly increase the rates of RBC antibody generation. Humoral alloimmunization begins with consumption of transfused RBCs by antigen‐presenting cells (APCs). Recently, it has become appreciated that there are multiple different types of APCs. The relative contribution of APC subsets to RBC antibodies has not been described in either the quiescent or the inflamed states.STUDY DESIGN AND METHODSTo evaluate the types of APCs that consume RBCs, and how inflammation affects this process, C56Bl/6 mice were treated with polyinosinic‐polycytidylic acid (poly(I:C)) to induce an inflammatory response and/or were transfused with 3,3′‐dihexadecyloxacarbocyanine perchlorate–labeled syngeneic RBCs. Erythrophagocytosis (both at baseline and during inflammation) was analyzed for different subsets of macrophages (MΦ), dendritic cells (DCs), B cells, and monocytes, by a combined approach using flow cytometry and fluorescent microscopy technology.RESULTSIn four independent experiments, erythrophagocytosis at baseline was predominately performed by red pulp MΦ; however, during inflammation both plasmacytoid DCs (pDCs) and monocytes increased RBC consumption. Furthermore, pDCs up regulated MHC‐II and activation markers CD80 and CD86. In addition to changing patterns of erythrophagocytosis, inflammation also led to a significant decrease in CD11c+ conventional DC populations and an increase in granulocytes.CONCLUSIONSThe nature of APCs that consume transfused RBCs is changed by inflammation. Given that APCs initiate humoral immune responses, these findings provide potential mechanistic insight into how inflammation regulates RBC alloimmunization.
Spinal inhibition and motor function in adults with spastic cerebral palsy
Authors: Condliffe E. G. , Jeffery D. T. , Emery D. J. , Gorassini M. A. 
Published: February 2016

Key points
Abnormal activation of motoneurons in the spinal cord by sensory pathways is thought to contribute to impaired movement control and spasticity in individuals with cerebral palsy.
Here we use single motor unit recordings to show how individual motoneurons in the spinal cord respond to sensory inputs in a group of participants with cerebral palsy having different degrees of motor dysfunction.
In participants who had problems walking independently and required assistive devices such as wheelchairs, sensory pathways only excited motoneurons in the spinal cord.
In contrast, in participants with cerebral palsy who walked independently for long distances, sensory inputs both inhibited and excited motoneurons in the spinal cord, similar to what we found in uninjured control participants.
These findings demonstrate that in individuals with severe cerebral palsy, inhibitory control of motoneurons from sensory pathways is reduced and may contribute to motor dysfunction and spasticity.
AbstractReduced inhibition of spinal motoneurons by sensory pathways may contribute to heightened reflex activity, spasticity and impaired motor function in individuals with cerebral palsy (CP). To measure if the activation of inhibitory post‐synaptic potentials (IPSPs) by sensory inputs is reduced in CP, the tonic discharge rate of single motor units from the soleus muscle was plotted time‐locked to the occurrence of a sensory stimulation to produce peri‐stimulus frequencygrams (PSFs). Stimulation to the medial arch of the foot was used to activate cutaneomuscular afferents in 17 adults with bilateral spastic CP and 15 neurologically intact (NI) peers. Evidence of IPSP activation from the PSF profiles, namely a marked pause or reduction in motor unit firing rates at the onset of the cutaneomuscular reflex, was found in all NI participants but in only half of participants with CP. In the other half of the participants with CP, stimulation of cutaneomuscular afferents produced a PSF profile indicative of a pure excitatory post‐synaptic potential, with firing rates increasing above the mean pre‐stimulus rate for 300 ms or more. The amplitude of motoneuron inhibition during the period of IPSP activation, as measured from the surface EMG, was less in participants with poor motor function as evaluated with the Gross Motor Functional Classification System (r = 0.72, P < 0.001) and the Functional Mobility Scale (r = −0.82, P < 0.001). These findings demonstrate that in individuals with CP, reduced activation of motoneuron IPSPs by sensory inputs is associated with reduced motor function and may contribute to enhanced reflexes and spasticity in CP.
Monte Carlo calculated correction factors for the PTW microDiamond detector in the Gamma Knife‐Model C
Authors: Barrett J. C. , Knill Cory 
Published: February 2016

Purpose:Accurate dose measurements in small fields require correction factors when sufficient CPE is not present inside of the field. These factors adjust for perturbation, volume averaging, and other effects; as such, they are field size, detector, and phantom dependent. In this work, Monte Carlo (MC) methods were used to calculate correction factors for PTW's microDiamond detector in Elekta's Gamma Knife Model‐C unit. These correction factors allow for accurate measurement of output factors—even in the smallest field sizes where CPE is not present.Methods:The small field correction factors were calculated as correction factors according to the Alfonso formalism. The MC model of the Gamma Knife was built with the EGSnrc code system, using BEAMnrc and DOSRZnrc user codes. Efforts were made to validate the MC model against experimental measurements. Using the model, field output factors and measurement ratios for each of the four helmet sizes were simulated for an ABS plastic phantom and validated against film measurements, detector measurements, and treatment planning system (TPS) data. Once validated against the available ABS phantom, the model was applied to a more waterlike solid water phantom. Using MC results from the solid water phantom, the final k correction factors were determined relative to the machine specific reference field—the 18 mm helmet, which is the largest field size available on the unit.Results:When validating against experimental measurements using the ABS phantom, all MC methods agreed with experiment within the stated uncertainties: MC determined field output factors agreed within 0.6% of the TPS and 1.4% of film; and MC simulated measurement ratios matched physically measured ratios within 1% for all helmet sizes. for the PTW microDiamond in the solid water phantom approached unity to within 0.4% ± 1.7% for all the helmet sizes except the 4 mm; the 4 mm helmet size over‐responded by 3.2% ± 1.7%, resulting in a of 0.969.Conclusions:Similar to what has been found in the Gamma Knife Perfexion, the PTW microDiamond over‐responds in the smallest 4 mm field. The over‐response can be corrected via the Alfonso formalism using the correction factors determined in this work. Using the MC calculated correction factors, the PTW microDiamond detector is an effective dosimeter in all available helmet sizes.
Postoperative 3D spine reconstruction by navigating partitioning manifolds
Authors: Kadoury Samuel , Labelle Hubert , Parent Stefan 
Published: February 2016

Purpose:The postoperative evaluation of scoliosis patients undergoing corrective treatment is an important task to assess the strategy of the spinal surgery. Using accurate 3D geometric models of the patient's spine is essential to measure longitudinal changes in the patient's anatomy. On the other hand, reconstructing the spine in 3D from postoperative radiographs is a challenging problem due to the presence of instrumentation (metallic rods and screws) occluding vertebrae on the spine.Methods:This paper describes the reconstruction problem by searching for the optimal model within a manifold space of articulated spines learned from a training dataset of pathological cases who underwent surgery. The manifold structure is implemented based on a multilevel manifold ensemble to structure the data, incorporating connections between nodes within a single manifold, in addition to connections between different multilevel manifolds, representing subregions with similar characteristics.Results:The reconstruction pipeline was evaluated on x‐ray datasets from both preoperative patients and patients with spinal surgery. By comparing the method to ground‐truth models, a 3D reconstruction accuracy of 2.24 ± 0.90 mm was obtained from 30 postoperative scoliotic patients, while handling patients with highly deformed spines.Conclusions:This paper illustrates how this manifold model can accurately identify similar spine models by navigating in the low‐dimensional space, as well as computing nonlinear charts within local neighborhoods of the embedded space during the testing phase. This technique allows postoperative follow‐ups of spinal surgery using personalized 3D spine models and assess surgical strategies for spinal deformities.
Clinical introduction of image lag correction for a cone beam CT system
Authors: Stankovic Uros , Ploeger Lennert S. , Sonke Jan‐Jakob , van Herk Marcel 
Published: February 2016

Purpose:Image lag in the flat‐panel detector used for Linac integrated cone beam computed tomography (CBCT) has a degrading effect on CBCT image quality. The most prominent visible artifact is the presence of bright semicircular structure in the transverse view of the scans, known also as radar artifact. Several correction strategies have been proposed, but until now the clinical introduction of such corrections remains unreported. In November 2013, the authors have clinically implemented a previously proposed image lag correction on all of their machines at their main site in Amsterdam. The purpose of this study was to retrospectively evaluate the effect of the correction on the quality of CBCT images and evaluate the required calibration frequency.Methods:Image lag was measured in five clinical CBCT systems (Elekta Synergy 4.6) using an in‐house developed beam interrupting device that stops the x‐ray beam midway through the data acquisition of an unattenuated beam for calibration. A triple exponential falling edge response was fitted to the measured data and used to correct image lag from projection images with an infinite response. This filter, including an extrapolation for saturated pixels, was incorporated in the authors' in‐house developed clinical cbct reconstruction software. To investigate the short‐term stability of the lag and associated parameters, a series of five image lag measurement over a period of three months was performed. For quantitative analysis, the authors have retrospectively selected ten patients treated in the pelvic region. The apparent contrast was quantified in polar coordinates for scans reconstructed using the parameters obtained from different dates with and without saturation handling.Results:Visually, the radar artifact was minimal in scans reconstructed using image lag correction especially when saturation handling was used. In patient imaging, there was a significant reduction of the apparent contrast from 43 ± 16.7 to 15.5 ± 11.9 HU without the saturation handling and to 9.6 ± 12.1 HU with the saturation handling, depending on the date of the calibration. The image lag correction parameters were stable over a period of 3 months. The computational load was increased by approximately 10%, not endangering the fast in‐line reconstruction.Conclusions:The lag correction was successfully implemented clinically and removed most image lag artifacts thus improving the image quality. Image lag correction parameters were stable for 3 months indicating low frequency of calibration requirements.
Technical Note: Method to correlate whole‐specimen histopathology of radical prostatectomy with diagnostic MR imaging
Authors: McGrath Deirdre M. , Lee Jenny , Foltz Warren D. , Samavati Navid , Jewett Michael A. S. , van der Kwast Theo , Chung Peter , Ménard Cynthia , Brock Kristy K. 
Published: February 2016

Purpose:Validation of MRI‐guided tumor boundary delineation for targeted prostate cancer therapy is achieved via correlation with gold‐standard histopathology of radical prostatectomy specimens. Challenges to accurate correlation include matching the pathology sectioning plane with the in vivo imaging slice plane and correction for the deformation that occurs between in vivo imaging and histology. A methodology is presented for matching of the histological sectioning angle and position to the in vivo imaging slices.Methods:Patients (n = 4) with biochemical failure following external beam radiotherapy underwent diagnostic MRI to confirm localized recurrence of prostate cancer, followed by salvage radical prostatectomy. High‐resolution 3‐D MRI of the ex vivo specimens was acquired to determine the pathology sectioning angle that best matched the in vivo imaging slice plane, using matching anatomical features and implanted fiducials. A novel sectioning device was developed to guide sectioning at the correct angle, and to assist the insertion of reference dye marks to aid in histopathology reconstruction.Results:The percentage difference in the positioning of the urethra in the ex vivo pathology sections compared to the positioning in in vivo images was reduced from 34% to 7% through slicing at the best match angle. Reference dye marks were generated, which were visible in ex vivo imaging, in the tissue sections before and after processing, and in histology sections.Conclusions:The method achieved an almost fivefold reduction in the slice‐matching error and is readily implementable in combination with standard MRI technology. The technique will be employed to generate datasets for correlation of whole‐specimen prostate histopathology with in vivo diagnostic MRI using 3‐D deformable registration, allowing assessment of the sensitivity and specificity of MRI parameters for prostate cancer. Although developed specifically for prostate, the method is readily adaptable to other types of whole tissue specimen, such as mastectomy or liver resection.
Genetic Stability of Bacterial Artificial Chromosome-Derived Human Cytomegalovirus during Culture
In Vitro
Authors: Murrell Isa , Wilkie Gavin S. , Davison Andrew J. , Statkute Evelina , Fielding Ceri A. , Tomasec Peter , Wilkinson Gavin W. G. , Stanton Richard J. 
Published: February 2016

ABSTRACT

Clinical human cytomegalovirus (HCMV) strains invariably mutate when propagated
in vitro
. Mutations in gene RL13 are selected in all cell types, whereas in fibroblasts mutants in the UL128 locus (UL128L; genes UL128, UL130, and UL131A) are also selected. In addition, sporadic mutations are selected elsewhere in the genome in all cell types. We sought to investigate conditions under which HCMV can be propagated without incurring genetic defects. Bacterial artificial chromosomes (BACs) provide a stable, genetically defined source of viral genome. Viruses were generated from BACs containing the genomes of strains TR, TB40, FIX, and Merlin, as well as from Merlin-BAC recombinants containing variant nucleotides in UL128L from TB40-BAC4 or FIX-BAC. Propagation of viruses derived from TR-BAC, TB40-BAC4, and FIX-BAC in either fibroblast or epithelial cells was associated with the generation of defects around the prokaryotic vector, which is retained in the unique short (U
S
) region of viruses. This was not observed for Merlin-BAC, from which the vector is excised in derived viruses; however, propagation in epithelial cells was consistently associated with mutations in the unique long
b
′ (U
L
/
b
′) region, all impacting on gene UL141. Viruses derived from Merlin-BAC in fibroblasts had mutations in UL128L, but mutations occurred less frequently with recombinants containing UL128L nucleotides from TB40-BAC4 or FIX-BAC. Viruses derived from a Merlin-BAC derivative in which RL13 and UL128L were either mutated or repressed were remarkably stable in fibroblasts. Thus, HCMV containing a wild-type gene complement can be generated
in vitro
by deriving virus from a self-excising BAC in fibroblasts and repressing RL13 and UL128L.

IMPORTANCE
Researchers should aim to study viruses that accurately represent the causative agents of disease. This is problematic for HCMV because clinical strains mutate rapidly when propagated
in vitro
, becoming less cell associated, altered in tropism, more susceptible to natural killer cells, and less pathogenic. Following isolation from clinical material, HCMV genomes can be stabilized by cloning into bacterial artificial chromosomes (BACs), and then virus is regenerated by DNA transfection. However, mutations can occur not only during isolation prior to BAC cloning but also when virus is regenerated. We have identified conditions under which BAC-derived viruses containing an intact, wild-type genome can be propagated
in vitro
with minimal risk of mutants being selected, enabling studies of viruses expressing the gene complement of a clinical strain. However, even under these optimized conditions, sporadic mutations can occur, highlighting the advisability of sequencing the HCMV stocks used in experiments.