bluuebunny/crossref_metadata_2025 huggingface dataset:
3D Blur Discrimination
Authors: Subedar Mahesh M. , Karam Lina J.
Published: April 2016

Blur is an important attribute in the study and modeling of the human visual system. In the blur discrimination experiments, just-noticeable additional blur required to differentiate from the reference blur level is measured. The past studies on blur discrimination have measured the sensitivity of the human visual system to blur using two-dimensional (2D) test patterns. In this study, subjective tests are performed to measure blur discrimination thresholds using stereoscopic 3D test patterns. Specifically, how the binocular disparity affects the blur sensitivity is measured on a passive stereoscopic display. A passive stereoscopic display renders the left and right eye images in a row interleaved format. The subjects have to wear circularly polarized glasses to filter the appropriate images to the left and right eyes. Positive, negative, and zero disparity values are considered in these experiments. A positive disparity value projects the objects behind the display screen, a negative disparity value projects the objects in front of the display screen, and a zero disparity value projects the objects at the display plane. The blur discrimination thresholds are measured for both symmetric and asymmetric stereo viewing cases. In the symmetric viewing case, the same level of additional blur is applied to the left and right eye stimulus. In the asymmetric viewing case, different levels of additional blur are applied to the left and right eye stimuli. The results of this study indicate that, in the symmetric stereo viewing case, binocular disparity does not affect the blur discrimination thresholds for the selected 3D test patterns. As a consequence of these findings, we conclude that the models developed for 2D blur discrimination can be used for 3D blur discrimination. We also show that the Weber model provides a good fit to the blur discrimination threshold measurements for the symmetric stereo viewing case. In the asymmetric viewing case, the blur discrimination thresholds decreased, and the decrease in threshold values is found to be dominated by eye observing the higher blur.
Effects of laryngeal restriction on pharyngeal peristalsis and biomechanics: Clinical implications
Authors: Shaker Reza , Sanvanson Patrick , Balasubramanian Gokulakrishnan , Kern Mark , Wuerl Ashley , Hyngstrom Allison
Published: April 2016

To date, rehabilitative exercises aimed at strengthening the pharyngeal muscles have not been developed due to the inability to successfully overload and fatigue these muscles during their contraction, a necessary requirement for strength training. The purpose of this study was to test the hypothesis that applying resistance against anterosuperior movement of the hyolaryngeal complex will overload the pharyngeal muscles and by repetitive swallowing will result in their fatigue manifested by a reduction in pharyngeal peristaltic amplitude. Studies were done in two groups. In group 1 studies 15 healthy subjects (age: 42 ± 14 yr, 11 females) were studied to determine whether imposing resistance to swallowing using a handmade device can affect the swallow-induced hyolaryngeal excursion and related upper esophageal sphincter (UES) opening. In group 2, an additional 15 healthy subjects (age 56 ± 25 yr, 7 females) were studied to determine whether imposing resistance to the anterosuperior excursion of the hyolaryngeal complex induces fatigue manifested as reduction in pharyngeal contractile pressure during repeated swallowing. Analysis of the video recordings showed significant decrease in maximum deglutitive superior laryngeal excursion and UES opening diameter ( P < 0.01) due to resistive load. Consecutive swallows against the resistive load showed significant decrease in pharyngeal contractile integral (PhCI) values ( P < 0.01). Correlation analysis showed a significant negative correlation between PhCI and successive swallows, suggesting “fatigue” ( P < 0.001). In conclusion, repeated swallows against a resistive load induced by restricting the anterosuperior excursion of the larynx safely induces fatigue in pharyngeal peristalsis and thus has the potential to strengthen the pharyngeal contractile function.
Changes in gluconeogenesis and intracellular lipid accumulation characterize uremic human hepatocytes ex vivo
Authors: Li Meng , Ellis Ewa , Johansson Helene , Nowak Greg , Isaksson Bengt , Gnocchi Davide , Parini Paolo , Axelsson Jonas
Published: April 2016

It is well known that reduced glomerular filtration rate (GFR) leads to an increased risk of dyslipidemia, insulin resistance, and cardiovascular mortality. The liver is a central organ for metabolism, but its function in the uremic setting is still poorly characterized. We used human primary hepatocytes isolated from livers of nine donors with normal renal function to investigate perturbations in key metabolic pathways following exposure to uremic ( n = 8) or healthy ( n = 8) sera, and to serum-free control medium. Both uremic and healthy elicited consistent responses from hepatocytes from multiple donors and compared with serum-free control. However, at physiological insulin concentrations, uremic cells accumulated 56% more intracellular lipids. Also, when comparing uremic with healthy medium after culture, it contained more very-low-density lipoprotein-triglyceride and glucose. These changes were accompanied by decreased phosphorylation of AktS473. mRNA levels of key regulators of gluconeogenesis in uremic sera-treated hepatocytes such as phospho enolpyruvate carboxykinase 1 and glucose 6-phosphate were elevated. We also found increased expression of 11β-hydroxysteroid dehydrogenase mRNA in uremic cells, along with high phosphorylation of downstream p53 and phospholipase C-γ1Y783. Thus our ex vivo data suggest that the uremic hepatocytes rapidly develop a glycogenic and lipogenic condition accompanied by perturbations in a large number of signaling networks.
Impaired sodium-dependent adaptation of arterial stiffness in formerly preeclamptic women: the RETAP-vascular study
Authors: van der Graaf Anne Marijn , Paauw Nina D. , Toering Tsjitske J. , Feelisch Martin , Faas Marijke M. , Sutton Thomas R. , Minnion Magdalena , Lefrandt Joop. D. , Scherjon Sicco A. , Franx Arie , Navis Gerjan , Lely A. Titia
Published: April 2016

Women with a history of preeclampsia have an increased risk for cardiovascular diseases later in life. Persistent vascular alterations in the postpartum period might contribute to this increased risk. The current study assessed arterial stiffness under low sodium (LS) and high sodium (HS) conditions in a well-characterized group of formerly early-onset preeclamptic (fPE) women and formerly pregnant (fHP) women. Eighteen fHP and 18 fPE women were studied at an average of 5 yr after pregnancy on 1 wk of LS (50 mmol Na+/day) and 1 wk of HS (200 mmol Na+/day) intake. Arterial stiffness was measured by pulse-wave analysis (aortic augmentation index, AIx) and carotid-femoral pulse-wave velocity (PWV). Circulating markers of the renin-angiotensin aldosterone system (RAAS), extracellular volume (ECV), nitric oxide (NO), and hydrogen sulfide (H2S) were measured in an effort to identify potential mechanistic elements underlying adaptation of arterial stiffness. AIx was significantly lower in fHP women on LS compared with HS while no difference in AIx was apparent in fPE women. PWV remained unchanged upon different sodium loads in either group. Comparable sodium-dependent changes in RAAS, ECV, and NO/H2S were observed in fHP and fPE women. fPE women have an impaired ability to adapt their arterial stiffness in response to changes in sodium intake, independently of blood pressure, RAAS, ECV, and NO/H2S status. The pathways involved in impaired adaptation of arterial stiffness, and its possible contribution to the increased long-term risk for cardiovascular diseases in fPE women, remain to be investigated.

Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/vascular-health-after-preeclampsia/ .
Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores
Authors: Asson-Batres Mary Ann , Ryzhov Sergey , Tikhomirov Oleg , Duarte Christine W. , Congdon Clare Bates , Lessard Craig R. , McFarland Samuel , Rochette-Egly Cecile , Tran Truc-Linh , Galindo Cristi L. , Favreau-Lessard Amanda J. , Sawyer Douglas B.
Published: April 2016

To determine whether hepatic depletion of vitamin A (VA) stores has an effect on the postnatal heart, studies were carried out with mice lacking liver retinyl ester stores fed either a VA-sufficient (LRVAS) or VA-deficient (LRVAD) diet (to deplete circulating retinol and extrahepatic stores of retinyl esters). There were no observable differences in the weights or gross morphology of hearts from LRVAS or LRVAD mice relative to sex-matched, age-matched, and genetically matched wild-type (WT) controls fed the VAS diet (WTVAS), but changes in the transcription of functionally relevant genes were consistent with a state of VAD in LRVAS and LRVAD ventricles. In silico analysis revealed that 58/67 differentially expressed transcripts identified in a microarray screen are products of genes that have DNA retinoic acid response elements. Flow cytometric analysis revealed a significant and cell-specific increase in the number of proliferating Sca-1 cardiac progenitor cells in LRVAS animals relative to WTVAS controls. Before myocardial infarction, LRVAS and WTVAS mice had similar cardiac systolic function and structure, as measured by echocardiography, but, unexpectedly, repeat echocardiography demonstrated that LRVAS mice had less adverse remodeling by 1 wk after myocardial infarction. Overall, the results demonstrate that the adult heart is responsive to retinoids, and, most notably, reducing hepatic VA stores (while maintaining circulating levels of VA) impacts ventricular gene expression profiles, progenitor cell numbers, and response to injury.
Aerobic exercise augments muscle transcriptome profile of resistance exercise
Authors: Lundberg Tommy R. , Fernandez-Gonzalo Rodrigo , Tesch Per A. , Rullman Eric , Gustafsson Thomas
Published: April 2016

Recent reports suggest that aerobic exercise may boost the hypertrophic response to short-term resistance training. This study explored the effects of an acute aerobic exercise bout on the transcriptional response to subsequent resistance exercise. Ten moderately trained men performed ∼45 min cycling on one leg followed by 4 × 7 maximal knee extensions for each leg, 15 min later. Thus, one limb performed aerobic and resistance exercise (AE + RE) while the opposing leg did resistance exercise only (RE). Biopsies were obtained from the vastus lateralis muscle of each leg 3 h after the resistance exercise bout. Using DNA microarray, we analyzed differences [≥1.5-fold, false discovery rate (FDR) ≤10%] in gene expression profiles for the two modes of exercise. There were 176 genes up (127)- or downregulated (49) by AE + RE compared with RE. Among the most significant differentially expressed genes were established markers for muscle growth and oxidative capacity, novel cytokines, transcription factors, and micro-RNAs (miRNAs). The most enriched functional categories were those linked to carbohydrate metabolism and transcriptional regulation. Upstream analysis revealed that vascular endothelial growth factor, cAMP-response element-binding protein, Tet methylcytosine dioxygenase, and mammalian target of rapamycin were regulators highly activated by AE + RE, whereas JnK, NF-κβ, MAPK, and several miRNAs were inhibited. Thus, aerobic exercise alters the skeletal muscle transcriptional signature of resistance exercise to initiate important gene programs promoting both myofiber growth and improved oxidative capacity. These results provide novel insight into human muscle adaptations to diverse exercise modes and offer the very first genomic basis explaining how aerobic exercise may augment, rather than compromise, muscle growth induced by resistance exercise.
Periods of cardiovascular susceptibility to hypoxia in embryonic american alligators (Alligator mississippiensis)
Authors: Tate Kevin B. , Rhen Turk , Eme John , Kohl Zachary F. , Crossley Janna , Elsey Ruth M. , Crossley Dane A.
Published: April 2016

During embryonic development, environmental perturbations can affect organisms' developing phenotype, a process known as developmental plasticity. Resulting phenotypic changes can occur during discrete, critical windows of development. Critical windows are periods when developing embryos are most susceptible to these perturbations. We have previously documented that hypoxia reduces embryo size and increases relative heart mass in American alligator, and this study identified critical windows when hypoxia altered morphological, cardiovascular function and cardiac gene expression of alligator embryos. We hypothesized that incubation in hypoxia (10% O2) would increase relative cardiac size due to cardiac enlargement rather than suppression of somatic growth. We exposed alligator embryos to hypoxia during discrete incubation periods to target windows where the embryonic phenotype is altered. Hypoxia affected heart growth between 20 and 40% of embryonic incubation, whereas somatic growth was affected between 70 and 90% of incubation. Arterial pressure was depressed by hypoxic exposure during 50–70% of incubation, whereas heart rate was depressed in embryos exposed to hypoxia during a period spanning 70–90% of incubation. Expression of Vegf and PdgfB was increased in certain hypoxia-exposed embryo treatment groups, and hypoxia toward the end of incubation altered β-adrenergic tone for arterial pressure and heart rate. It is well known that hypoxia exposure can alter embryonic development, and in the present study, we have identified brief, discrete windows that alter the morphology, cardiovascular physiology, and gene expression in embryonic American alligator.
Metabolic rate and rates of protein turnover in food-deprived cuttlefish,Sepia officinalis(Linnaeus 1758)
Authors: Lamarre Simon G. , MacCormack Tyson J. , Sykes Antonio V. , Hall Jennifer R. , Speers-Roesch Ben , Callaghan Neal I. , Driedzic William R.
Published: April 2016

To determine the metabolic response to food deprivation, cuttlefish ( Sepia officinalis) juveniles were either fed, fasted (3 to 5 days food deprivation), or starved (12 days food deprivation). Fasting resulted in a decrease in triglyceride levels in the digestive gland, and after 12 days, these lipid reserves were essentially depleted. Oxygen consumption was decreased to 53% and NH4excretion to 36% of the fed group following 3–5 days of food deprivation. Oxygen consumption remained low in the starved group, but NH4excretion returned to the level recorded for fed animals during starvation. The fractional rate of protein synthesis of fasting animals decreased to 25% in both mantle and gill compared with fed animals and remained low in the mantle with the onset of starvation. In gill, however, protein synthesis rate increased to a level that was 45% of the fed group during starvation. In mantle, starvation led to an increase in cathepsin A-, B-, H-, and L-like enzyme activity and a 2.3-fold increase in polyubiquitin mRNA that suggested an increase in ubiquitin-proteasome activity. In gill, there was a transient increase in the polyubiquitin transcript levels in the transition from fed through fasted to the starved state and cathepsin A-, B-, H-, and L-like activity was lower in starved compared with fed animals. The response in gill appears more complex, as they better maintain rates of protein synthesis and show no evidence of enhanced protein breakdown through recognized catabolic processes.
Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway
Authors: Bordicchia M. , Ceresiani M. , Pavani M. , Minardi D. , Polito M. , Wabitsch M. , Cannone V. , Burnett J. C. , Dessì-Fulgheri P. , Sarzani R.
Published: April 2016

Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes.
Extracellular purines' action on glomerular albumin permeability in isolated rat glomeruli: insights into the pathogenesis of albuminuria
Authors: Kasztan Małgorzata , Piwkowska Agnieszka , Kreft Ewelina , Rogacka Dorota , Audzeyenka Irena , Szczepanska-Konkel Mirosława , Jankowski Maciej
Published: April 2016

Purinoceptors (adrengeric receptors and P2 receptors) are expressed on the cellular components of the glomerular filtration barrier, and their activation may affect glomerular permeability to albumin, which may ultimately lead to albuminuria, a well-established risk factor for the progression of chronic kidney disease and development of cardiovascular diseases. We investigated the mechanisms underlying the in vitro and in vivo purinergic actions on glomerular filter permeability to albumin by measuring convectional albumin permeability ( Palb) in a single isolated rat glomerulus based on the video microscopy method. Primary cultured rat podocytes were used for the analysis of Palb, cGMP accumulation, PKG-Iα dimerization, and immunofluorescence. In vitro, natural nucleotides (ATP, ADP, UTP, and UDP) and nonmetabolized ATP analogs (2-meSATP and ATP-γ-S) increased Palbin a time- and concentration-dependent manner. The effects were dependent on P2 receptor activation, nitric oxide synthase, and cytoplasmic guanylate cyclase. ATP analogs significantly increased Palb, cGMP accumulation, and subcortical actin reorganization in a PKG-dependent but nondimer-mediated route in cultured podocytes. In vivo, 2-meSATP and ATP-γ-S increased Palbbut did not significantly affect urinary albumin excretion. Both agonists enhanced the clathrin-mediated endocytosis of albumin in podocytes. A product of adenine nucleotides hydrolysis, adenosine, increased the permeability of the glomerular barrier via adrenergic receptors in a dependent and independent manner. Our results suggest that the extracellular nucleotides that stimulate an increase of glomerular Palbinvolve nitric oxide synthase and cytoplasmic guanylate cyclase with actin reorganization in podocytes.
Accuracy and robustness of a simple algorithm to measure vessel diameter from B-mode ultrasound images
Authors: Hunt Brian E. , Flavin Daniel C. , Bauschatz Emily , Whitney Heather M.
Published: April 2016

Measurement of changes in arterial vessel diameter can be used to assess the state of cardiovascular health, but the use of such measurements as biomarkers is contingent upon the accuracy and robustness of the measurement. This work presents a simple algorithm for measuring diameter from B-mode images derived from vascular ultrasound. The algorithm is based upon Gaussian curve fitting and a Viterbi search process. We assessed the accuracy of the algorithm by measuring the diameter of a digital reference object (DRO) and ultrasound-derived images of a carotid artery. We also assessed the robustness of the algorithm by manipulating the quality of the image. Across a broad range of signal-to-noise ratio and with varying image edge error, the algorithm measured vessel diameter within 0.7% of the creation dimensions of the DRO. This was a similar level of difference (0.8%) to when an ultrasound image was used. When SNR dropped to 18 dB, measurement error increased to 1.3%. When edge position was varied by as much as 10%, measurement error was well maintained between 0.68 and 0.75%. All these errors fall well within the margin of error established by the medical physics community for quantitative ultrasound measurements. We conclude that this simple algorithm provides consistent and accurate measurement of lumen diameter from B-mode images across a broad range of image quality.
Pressure distension in leg vessels as influenced by prolonged bed rest and a pressure habituation regimen
Authors: Eiken Ola , Mekjavic Igor B. , Kounalakis Stylianos N. , Kölegård Roger
Published: April 2016

Bed rest increases pressure distension in arteries, arterioles, and veins of the leg. We hypothesized that bed-rest-induced deconditioning of leg vessels is governed by the removal of the local increments in transmural pressure induced by assuming erect posture and, therefore, can be counteracted by intermittently increasing local transmural pressure during the bed rest. Ten men underwent 5 wk of horizontal bed rest. A subatmospheric pressure (−90 mmHg) was intermittently applied to one lower leg [pressure habituation (PH) leg]. Vascular pressure distension was investigated before and after the bed rest, both in the PH and control (CN) leg by increasing local distending pressure, stepwise up to +200 mmHg. Vessel diameter and blood flow were measured in the posterior tibial artery and vessel diameter in the posterior tibial vein. In the CN leg, bed rest led to 5-fold and 2.7-fold increments ( P < 0.01) in tibial artery pressure-distension and flow responses, respectively, and to a 2-fold increase in tibial vein pressure distension. In the PH leg, arterial pressure-distension and flow responses were unaffected by bed rest, whereas bed rest led to a 1.5-fold increase in venous pressure distension. It thus appears that bed-rest-induced deconditioning of leg arteries, arterioles, and veins is caused by removal of gravity-dependent local pressure loads and may be abolished or alleviated by a local pressure-habituation regimen.
ATM protein is located on presynaptic vesicles and its deficit leads to failures in synaptic plasticity
Authors: Vail Graham , Cheng Aifang , Han Yu Ray , Zhao Teng , Du Shengwang , Loy Michael M. T. , Herrup Karl , Plummer Mark R.
Published: April 2016

Ataxia telangiectasia is a multisystemic disorder that includes a devastating neurodegeneration phenotype. The ATM (ataxia-telangiectasia mutated) protein is well-known for its role in the DNA damage response, yet ATM is also found in association with cytoplasmic vesicular structures: endosomes and lysosomes, as well as neuronal synaptic vesicles. In keeping with this latter association, electrical stimulation of the Schaffer collateral pathway in hippocampal slices from ATM-deficient mice does not elicit normal long-term potentiation (LTP). The current study was undertaken to assess the nature of this deficit. Theta burst-induced LTP was reduced in Atm−/− animals, with the reduction most pronounced at burst stimuli that included 6 or greater trains. To assess whether the deficit was associated with a pre- or postsynaptic failure, we analyzed paired-pulse facilitation and found that it too was significantly reduced in Atm−/− mice. This indicates a deficit in presynaptic function. As further evidence that these synaptic effects of ATM deficiency were presynaptic, we used stochastic optical reconstruction microscopy. Three-dimensional reconstruction revealed that ATM is significantly more closely associated with Piccolo (a presynaptic marker) than with Homer1 (a postsynaptic marker). These results underline how, in addition to its nuclear functions, ATM plays an important functional role in the neuronal synapse where it participates in the regulation of presynaptic vesicle physiology.
Can Impaired Elasticity of Aorta Predict the Success of Vardenafil Treatment in Patients with Erectile Dysfunction?
Authors: Ede Hüseyin , Tanik Serhat , Yaylak Barış , Zengın Kürşad , Albayrak Sebahattin , Akkaya Suleyman , Polat Cegergun , Turan Yaşar , Erbay Alirıza
Published: April 2016

Objective. Vardenafil is used in treatment of erectile dysfunction (ED) but reveals variable clinical outcomes. Here, we aimed to evaluate the role of aortic elasticity in predicting vardenafil success among patients with ED.Methods. Sixty-one consecutive male subjects with primary ED and indication for vardenafil treatment were included. All subjects fulfilled 5-item version of the International Index of Erectile Function (IIEF-5) before the vardenafil treatment. Pretreatment aortic stiffness index (ASI) and aortic distensibility (AD) were obtained echocardiographically. Following two-month vardenafil treatment, the patients were reevaluated with IIEF-5. Pretreatment, posttreatment, and ΔIIEF-5 scores and ASI values were compared.Results. Average age was54±8years. Pretreatment and posttreatment IIEF-5 and ΔIIEF-5 scores were9.1±2.5;18.5±2.3; and9.4±3, respectively. Mean ASI and AD values were3.10±0.54and4.13±2.551/(103  ×  mmHg) accordingly. ASI value of severe pretreatment ED (n=15) was significantly higher than that of mild-moderate pretreatment ED (n=12) (p<0.001). All pretreatment IIEF-5 scores increased significantly compared to posttreatment IIEF-5 scores (p<0.001). ASI values were significantly correlated to pretreatment IIEF-5 scores (p<0.001) and ΔIIEF-5 value (p<0.001) but not to posttreatment IIEF-5 score.Conclusion. Aortic elasticity was impaired in accordance with degree of ED. The subjects with higher ASI values obtained more benefits from vardenafil.
Support Vector Regression and Genetic Algorithm for HVAC Optimal Operation
Authors: Chen Ching-Wei , Chang Yung-Chung
Published: April 2016

This study covers records of various parameters affecting the power consumption of air-conditioning systems. Using the Support Vector Machine (SVM), the chiller power consumption model, secondary chilled water pump power consumption model, air handling unit fan power consumption model, and air handling unit load model were established. In addition, it was found thatR2of the models all reached 0.998, and the training time was far shorter than that of the neural network. Through genetic programming, a combination of operating parameters with the least power consumption of air conditioning operation was searched. Moreover, the air handling unit load in line with the air conditioning cooling load was predicted. The experimental results show that for the combination of operating parameters with the least power consumption in line with the cooling load obtained through genetic algorithm search, the power consumption of the air conditioning systems under said combination of operating parameters was reduced by 22% compared to the fixed operating parameters, thus indicating significant energy efficiency.
Identifying Antioxidant and Antimicrobial Activities of the Phenolic Extracts and Mineral Contents of Virgin Olive Oils (Olea europaeaL. cv. Edincik Su) from Different Regions in Turkey
Authors: Dağdelen Ayhan
Published: April 2016

The objective of this study was to identify the antioxidant and antimicrobial activities of the phenolic extracts and mineral contents of virgin olive oils (Olea europaeaL. cv. Edincik Su) obtained from three different locations, Edincik, Gomec, and Izmir, in Turkey. Antioxidant activity was analysed spectrometrically, antimicrobial effect was evaluated by disc diffusion method, and mineral contents were determined by using Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES). Total phenolic contents and free radical scavenging activities of Edincik Su olive cultivar were found between 159.99 and 189.64 mg gallic acid equivalent/kg and 21.76 and 31.79% inhibition of DPPH•radical values, respectively. Phenolic composition was also varied according to location and hydroxytyrosol and tyrosol were determined as major phenolic compounds. Fourteen pathogenic bacteria and two fungal strains were used to determine the antimicrobial activity. Phenolic extracts showed antimicrobial effect against a wide range of microorganisms and the descending rank of the antimicrobial activities was Gomec, Izmir, and Edincik samples. The highest antimicrobial activities were determined againstClostridium perfringensATCC 13124 andCampylobacter jejuniATCC  33291 in all samples. Sixteen elements were used as standards (eleven of them were heavy metals) to identify mineral contents. Fe, Mg, Sn, K, and Ca were determined in Gomec samples and Mg and K were detected in Edincik samples while no mineral content was detected in Izmir sample.
Improved Survival of HER2+ Breast Cancer Patients Treated with Trastuzumab and Chemotherapy Is Associated with Host Antibody Immunity against the HER2 Intracellular Domain
Authors: Knutson Keith L. , Clynes Raphael , Shreeder Barath , Yeramian Patrick , Kemp Kathleen P. , Ballman Karla , Tenner Kathleen S. , Erskine Courtney L. , Norton Nadine , Northfelt Donald , Tan Winston , Calfa Carmen , Pegram Mark , Mittendorf Elizabeth A. , Perez Edith A.
Published: April 2016

The addition of trastuzumab to chemotherapy extends survival among patients with HER2+ breast cancer. Prior work showed that trastuzumab and chemotherapy augments HER2 extracellular domain (ECD)-specific antibodies. The current study investigated whether combination therapy induced immune responses beyond HER2-ECD and, importantly, whether those immune responses were associated with survival. Pretreatment and posttreatment sera were obtained from 48 women with metastatic HER2+ breast cancer on NCCTG (now Alliance for Clinical Trials in Oncology) studies, N0337 and N983252. IgG to HER2 intracellular domain (ICD), HER2-ECD, p53, IGFBP2, CEA, and tetanus toxoid were examined. Sera from 25 age-matched controls and 26 surgically resected HER2+ patients were also examined. Prior to therapy, some patients with metastatic disease had elevated antibodies to IGFBP2, p53, HER2-ICD, HER2-ECD, and CEA, but not to tetanus toxin, relative to controls and surgically resected patients. Treatment augmented antibody responses to HER2-ICD in 69% of metastatic patients, which was highly associated with improved progression-free survival (PFS; HR = 0.5, P = 0.0042) and overall survival (OS; HR = 0.7, P = 0.038). Augmented antibody responses to HER2-ICD also correlated (P = 0.03) with increased antibody responses to CEA, IGFBP2, and p53, indicating that treatment induces epitope spreading. Paradoxically, patients who already had high preexisting immunity to HER2-ICD did not respond to therapy with increased antibodies to HER2-ICD and demonstrated poorer PFS (HR = 1.6, P < 0.0001) and OS (HR = 1.4, P = 0.0006). Overall, the findings further demonstrate the importance of the adaptive immune system in the efficacy of trastuzumab-containing regimens. Cancer Res; 76(13); 3702–10. ©2016 AACR.
PCBP1/HNRNP E1 Protects Chromosomal Integrity by Translational Regulation of CDC27
Authors: Link Laura A. , Howley Breege V. , Hussey George S. , Howe Philip H.
Published: April 2016

CDC27 is a core component of the anaphase-promoting complex/cyclosome (APC/C), a multisubunit E3 ubiquitin ligase, whose oscillatory activity is responsible for the metaphase-to-anaphase transition and mitotic exit. Here, in normal murine mammary gland epithelial cells (NMuMG), CDC27 expression is controlled posttranscriptionally through the RNA binding protein poly(rC) binding protein 1 (PCBP1)/heterogeneous nuclear ribonucleoprotein E1 (HNRNP E1). shRNA-mediated knockdown of HNRNP E1 abrogates translational silencing of the Cdc27 transcript, resulting in constitutive expression of CDC27. Dysregulated expression of CDC27 leads to premature activation of the G2–M–APC/C–CDC20 complex, resulting in the aberrant degradation of FZR1/CDH1, a cofactor of the G1 and late G2–M–APC/C and a substrate normally reserved for the SCF-βTRCP ligase. Loss of CDH1 expression and of APC/C-CDH1 activity, upon constitutive expression of CDC27, results in mitotic aberrations and aneuploidy in NMuMG cells. Furthermore, tissue microarray of breast cancer patient tumor samples reveals high CDC27 levels compared with nonneoplastic breast tissue and a significant correlation between disease recurrence and CDC27 expression. These results suggest that dysregulation of HNRNP E1-mediated translational regulation of Cdc27 leads to chromosomal instability and aneuploidy and that CDC27 expression represents a significant predictor of breast cancer recurrence.

Implications: The RNA-binding protein HNRNP E1 mediates translational regulation of the cell-cycle regulator CDC27 and that dysregulation of CDC27 leads to aneuploidy. In addition, high CDC27 expression in breast cancer patient tumor specimens significantly predicts disease recurrence, suggesting a novel role for CDC27 as a predictor of relapse. Mol Cancer Res; 14(7); 634–46. ©2016 AACR.
The Dose–Response Effects of Aerobic Exercise on Body Composition and Breast Tissue among Women at High Risk for Breast Cancer: A Randomized Trial
Authors: Brown Justin C. , Kontos Despina , Schnall Mitchell D. , Wu Shandong , Schmitz Kathryn H.
Published: April 2016

Observational data indicate that behaviors that shift energetic homeostasis, such as exercise, may decrease the risk of developing breast cancer by reducing the amount of energy-dense, metabolically active adipose tissue. Between December 2008 and April 2013, we conducted a single-blind, 5-month, clinical trial that randomized premenopausal women at high risk of developing breast cancer to one of three groups: 150 min/wk of aerobic exercise (low dose), 300 min/wk of aerobic exercise (high dose), or control. Body composition was assessed using dual-energy x-ray absorptiometry. Background parenchymal enhancement (BPE) was quantified using computerized algorithms on breast dynamic contrast-enhanced MRI. Over 5 months, compared with the control group: the low-dose and high-dose groups lost −1.5 ± 0.5 and −1.3 ± 0.5 kg of body mass (linear Ptrend = 0.032); −1.5 ± 0.4 and −1.4 ± 0.3 kg of fat mass (linear Ptrend = 0.003); −1.3 ± 0.3 and −1.4 ± 0.3% of body fat (linear Ptrend < 0.001); −15.9 ± 5.4 and −26.6 ± 5.0 cm2 of subcutaneous adipose tissue (linear Ptrend < 0.001); and −6.6 ± 1.9 and −5.0 ± 1.9 cm2 visceral adipose tissue (nonlinear Ptrend = 0.037). For each −1 cm2 reduction in visceral adipose tissue, BPE decreased by −3.43 ± 1.34 cm2 (P = 0.010) and explained 9.7% of the variability in BPE. Changes in other aforementioned body composition outcomes did not significantly correlate with changes in BPE. These mechanistic data support observational evidence that shifting energetic homeostasis through exercise may alter the risk of developing breast cancer. Additional adequately powered studies are needed to confirm and expand upon our findings that changes in body composition are associated with changes in BPE. Cancer Prev Res; 9(7); 581–8. ©2016 AACR.
Current Status of Whole-Slide Imaging in Education
Authors: Saco Adela , Bombi Jose Antoni , Garcia Adriana , Ramírez Jose , Ordi Jaume
Published: April 2016

Conventional light microscopy (CLM) has classically been the basic tool to teach histology and pathology. In recent years, whole-slide imaging (WSI), which consists of generating a high-magnification digital image of an entire histological glass slide, has emerged as a useful alternative to CLM offering a myriad of opportunities for education. Navigation through the digitized slides closely simulates viewing glass slides with a microscope and is also referred to as virtual microscopy. WSI has many advantages for education. Students feel more comfortable with its use, and it can be used in any classroom as it only requires a computer with Internet access and it allows remote access from anywhere and from any device. WSI can be used simultaneously by a large number of people, stimulating cooperation between students and improving the interaction with the teachers. It allows making marks and annotations on specific fields, which enable specific directed questions to the teacher. Finally, WSI supports are cost-effective compared with CLM. Consequently, WSI has begun to replace CLM in many institutions. WSI has shown to be an extremely useful tool for undergraduate education (medical, dental and veterinary schools), for the training of residents of pathology, tele-education and in tumor boards.
Validation of Whole-Slide Imaging for Histolopathogical Diagnosis: Current State
Authors: Saco Adela , Ramírez Jose , Rakislova Natalia , Mira Aurea , Ordi Jaume
Published: April 2016

Rapid advances in informatics and technological improvements have led to the development of high-throughput whole-slide imaging (WSI) scanners able to produce high-quality digital images, which allow achieving a correct diagnosis of the biopsies using virtual viewers. This technology is currently prepared to be introduced in the departments of pathology for routine diagnosis. The aim of this review is to analyze the current evidence regarding the use of WSI in primary or routine diagnosis in the different subspecialties of pathology. An increasing number of studies have shown almost perfect inter- and intraobserver agreement between the diagnoses obtained with WSI and the classical diagnoses based on conventional light microscopy. The only exception seems to be cytology, which still requires some technological development. Although validation studies are needed in some areas of pathology, growing evidence indicates that WSI is a reliable tool for routine diagnosis. Pathologists have a positive perception of the ergonomics of the workstations, the low magnification of WSI and the possibility of making annotations and measurements. WSI can be used from any device and anywhere, thereby providing great opportunities for teleconsultation. New technologies such as the recognition of histopathology patterns using image analysis may facilitate diagnosis and improve the reproducibility among pathologists in the future.
Sites of Successful Ventricular Fibrillation Ablation in Bileaflet Mitral Valve Prolapse Syndrome
Authors: Syed Faisal F. , Ackerman Michael J. , McLeod Christopher J. , Kapa Suraj , Mulpuru Siva K. , Sriram Chenni S. , Cannon Bryan C. , Asirvatham Samuel J. , Noseworthy Peter A.
Published: April 2016

Background—

Although the vast majority of mitral valve prolapse (MVP) is benign, a small subset of patients, predominantly women, with bileaflet prolapse, complex ventricular ectopy (VE), and abnormal T waves comprise the recently described bileaflet MVP syndrome. We compared findings on electrophysiological study in bileaflet MVP syndrome patients with and without cardiac arrest to identify factors that may predispose to malignant ventricular arrhythmia.

Methods and Results—

Fourteen consecutive bileaflet MVP syndrome patients (n=13 women; median [limits], age at index ablation, 33.8 [21.0–58.7] years; ejection fraction, 60% [45%–67%]; all ≤ moderate mitral regurgitation; n=6 with previous cardiac arrest and implantable cardioverter defibrillator shocks for ventricular fibrillation; and n=8 without implantable cardioverter defibrillator although with symptomatic complex VE) were included. The 2 groups had similar baseline echocardiographic and electrocardiographic characteristics. All patients had at least 1 left ventricular papillary or fascicular VE focus. Purkinje origin VE was identified as the ventricular fibrillation trigger in 6 of 6 cardiac arrest patients (4 from papillary muscle) and Purkinje origin of dominant VE was seen in 5 of 8 (3 from papillary muscle) nonarrest patients. Acute success was seen in 17 of 19 procedures, and a ventricular fibrillation storm occurred within 24 hours of ablation in a single patient. Repeat ablation for recurrent symptomatic arrhythmia was performed in 6 patients. At 478 (39–2099) days of follow-up, 2 cardiac arrest patients received appropriate shocks. Symptoms from VE were reduced in 12 of 14.

Conclusions—

Bileaflet MVP syndrome is characterized by fascicular and papillary muscle VE that triggers ventricular fibrillation. Ablation of clinically dominant VE foci improves symptoms and reduces appropriate implantable cardioverter defibrillator shocks.
Two‐Pore K
+
Channel TREK‐1 Regulates Sinoatrial Node Membrane Excitability
Authors: Unudurthi Sathya D. , Wu Xiangqiong , Qian Lan , Amari Foued , Onal Birce , Li Ning , Makara Michael A. , Smith Sakima A. , Snyder Jedidiah , Fedorov Vadim V. , Coppola Vincenzo , Anderson Mark E. , Mohler Peter J. , Hund Thomas J.
Published: April 2016

Background

Two‐pore K
+
channels have emerged as potential targets to selectively regulate cardiac cell membrane excitability; however, lack of specific inhibitors and relevant animal models has impeded the effort to understand the role of 2‐pore K
+
channels in the heart and their potential as a therapeutic target. The objective of this study was to determine the role of mechanosensitive 2‐pore K
+
channel family member
TREK
‐1 in control of cardiac excitability.

Methods and Results

Cardiac‐specific
TREK
‐1–deficient mice (α
MHC
‐
Kcnk
f/f
) were generated and found to have a prevalent sinoatrial phenotype characterized by bradycardia with frequent episodes of sinus pause following stress. Action potential measurements from isolated α
MHC
‐
Kcnk2
f/f
sinoatrial node cells demonstrated decreased background K
+
current and abnormal sinoatrial cell membrane excitability. To identify novel pathways for regulating
TREK
‐1 activity and sinoatrial node excitability, mice expressing a truncated allele of the
TREK
‐1–associated cytoskeletal protein β

IV

‐spectrin (
qv

4J

mice) were analyzed and found to display defects in cell electrophysiology as well as loss of normal
TREK
‐1 membrane localization. Finally, the β

IV

‐spectrin/
TREK
‐1 complex was found to be downregulated in the right atrium from a canine model of sinoatrial node dysfunction and in human cardiac disease.

Conclusions

These findings identify a
TREK
‐1–dependent pathway essential for normal sinoatrial node cell excitability that serves as a potential target for selectively regulating sinoatrial node cell function.
Comparative Effectiveness of Generic Atorvastatin and Lipitor
®
in Patients Hospitalized with an Acute Coronary Syndrome
Authors: Jackevicius Cynthia A. , Tu Jack V. , Krumholz Harlan M. , Austin Peter C. , Ross Joseph S. , Stukel Therese A. , Koh Maria , Chong Alice , Ko Dennis T.
Published: April 2016

Background

Although generic medications are approved based on bioequivalence with brand‐name medications, there remains substantial concern regarding their clinical effectiveness and safety. Lipitor
®
, available as generic atorvastatin, is one of the most commonly prescribed statins. Therefore, we compared the effectiveness of generic atorvastatin products and Lipitor
®
.

Methods and Results

We conducted a population‐based cohort study, using propensity score matching to minimize potential confounding of patients ≥65 years, discharged alive after acute coronary syndrome (
ACS)
hospitalization between 2008 and 2012 in Ontario, Canada, who were prescribed Lipitor
®
or generic atorvastatin within 7 days of discharge. The primary outcome was 1‐year death/recurrent
ACS
hospitalization. Secondary outcomes included hospitalization for heart failure, stroke, new‐onset diabetes, rhabdomyolysis, and renal failure. In the 7863 propensity‐matched pairs (15 726 patients), mean age was 76.9 years, 56.3% were male, 87.6% had myocardial infarction, and all patients had complete follow‐up. At 1 year, 17.7% of those prescribed generic atorvastatin and 17.7% of those prescribed Lipitor
®
experienced death or recurrent
ACS
(hazard ratio, 1.00; 95%
CI
, 0.93–1.08;
P
=0.94). No significant differences in rates of secondary outcomes between groups were observed. Prespecified subgroup analyses by age, sex, diabetes, atorvastatin dose, or admission diagnosis found no outcome difference between groups.

Conclusions

Among older adults discharged alive after
ACS
hospitalization, we found no significant difference in cardiovascular outcomes or serious, infrequent side effects in patients prescribed generic atorvastatin compared with those prescribed Lipitor
®
at 1 year. Our findings support the use of generic atorvastatin in
ACS
, which could lead to substantial cost saving for patients and health care plans without diminishing population clinical effectiveness.
Texts, Themes, and Theologies: A Response to John Goldingay’s The Theology of the Book of Isaiah
Authors: Davies Andrew
Published: April 2016

This review offers a critical reading of John Goldingay’s The Theology of the Book of Isaiah from the author’s perspective as a Pentecostal literary critic and exegete. Focussing on Goldingay’s distinction between meaning and significance, it commends Goldingay’s attention to the difference between the theologies in the book of Isaiah and a variety of theologies which might be seen as arising from the book, and draws out some fundamental questions which Goldingay’s observations pose more broadly for Pentecostal interpreters.
The Ignatian Mystic and the Isaiah Scholar: A Response to John Goldingay’s The Theology of the Book of Isaiah
Authors: Green Chris E.W.
Published: April 2016

In and with the many rich gifts it affords, John Goldingay’s theology of Isaiah forces a series of pressing questions about the nature of Scripture as witness to Christ and the Christian gospel as well as about the character and purpose of Christian readings of the Hebrew Scriptures and the place of Christian doctrine in the practice of faithful interpretation. This paper attempts not only to draw attention to these questions but also to show why they matter and to provide at least the beginnings of an alternative approach to reading Isaiah and other ot texts, largely through appeal to other of Goldingay’s works.
On the Variation of the Effective Breaking Strength in Oceanic Sea States
Authors: Zappa Christopher J. , Banner Michael L. , Morison Russel P. , Brumer Sophia E.
Published: April 2016

A spectral framework for quantifying the geometric/kinematic and dynamic/energetic properties of breaking ocean waves was proposed by Phillips in 1985. Phillips assumed a constant breaking strength coefficient to link the kinematic/geometric breaking crest properties to the associated excess energy and momentum fluxes from the waves to the upper ocean. However, a scale-dependent (spectral) breaking strength coefficient is needed, but is unavailable from measurements. In this paper, the feasibility of a parametric mean effective breaking strength coefficient valid for a wide range of sea states is investigated. All available ocean breaking wave datasets were analyzed and complemented with wave model behavior. Robust evidence is found supporting a single linear parameter relationship between the effective breaking strength and wave age or significant wave steepness. Envisaged applications for the effective breaking strength are described.