Knock-out reactions

International Nuclear Information System (INIS)

de Forest, T. Jr.

1977-01-01

It is pointed out that the primary motivation for performing high energy single nucleon knock-out reactions is based on the concept of quasi-elastic scattering. The validity of and corrections to the partial wave impulse approximation and kinematical invariance of knock-out reactions and tests of the reaction mechanism are treated. The effect of distortions on the momentum distribution in the effective momentum approximation for given parameters are plotted. 12 references

Extracorporeal Cardiopulmonary Resuscitation Among Patients with Structurally Normal Hearts.

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Conrad, Stephanie J; Bridges, Brian C; Kalra, Yuvraj; Pietsch, John B; Smith, Andrew H

Extracorporeal cardiopulmonary resuscitation (eCPR) has been well described as a rescue therapy in refractory cardiac arrest among patients with congenital heart disease. The purpose of this retrospective analysis of data from the Extracorporeal Life Support Organization was to evaluate outcomes of eCPR in patients with structurally normal hearts and to identify risk factors that may contribute to mortality. During the study period, 1,431 patients met inclusion criteria. Median age was 16 years. Overall survival to hospital discharge was 32%. Conditional logistic regression demonstrated an independent survival benefit among smaller patients, patients with a lower partial pressure of carbon dioxide (PaCO2) on cannulation, and those with a shorter duration from intubation to eCPR cannulation. A diagnosis of sepsis was independently associated with a nearly threefold increase in odds of mortality, whereas the diagnosis of myocarditis portended a more favorable outcome. Neurologic complications, pulmonary hemorrhage, disseminated intravascular coagulation, CPR, pH less than 7.20, and hyperbilirubinemia after eCPR cannulation were independently associated with an increase in odds of mortality. When utilizing eCPR in patients with structurally normal hearts, a diagnosis of sepsis is independently associated with mortality, whereas a diagnosis of myocarditis is protective. Neurologic complications and pulmonary hemorrhage while on extracorporeal membrane oxygenation (ECMO) are independently associated with mortality.

The interactions between IC engine thermodynamics and knock

International Nuclear Information System (INIS)

Caton, Jerald A.

2017-01-01

Highlights: • Importance of engine thermodynamics regarding knock was quantified. • Effects of compression ratio, engine speed and EGR on knock was reported. • Retarding combustion to avoid knock resulted in decreases of efficiency. - Abstract: The development of high efficiency spark-ignition internal combustion engines is often constrained by the occurrence of knock. Knock may result in engine damage, lower performance, and lower efficiency. The options for preventing knock often involve lower compression ratios, lower boost, retarded spark timing, and other design choices that are detrimental to engine performance and efficiency. Since knock is largely a function of the thermodynamic state of the unburned zone, the occurrence of knock is expected to be a strong function of the engine thermodynamics. The purpose of the current work is to couple a simple knock model with a comprehensive engine cycle simulation to determine the interactions between the engine thermodynamics and knock. This work has explored the effects of engine parameters such as compression ratio (4–12), engine speed (500–2500 rpm), inlet pressure (50–100 kPa), exhaust gas recirculation (0–25%), combustion duration and heat transfer on knock. In each case, the occurrence of knock is connected to the cylinder pressures and the gas temperatures of the unburned zone. For example for a compression ratio of 12, to avoid knock the brake thermal efficiency decreased from 36.5% to 34% due to retarding the combustion.

Inducible Knock-Down of the Mineralocorticoid Receptor in Mice Disturbs Regulation of the Renin-Angiotensin-Aldosterone System and Attenuates Heart Failure Induced by Pressure Overload.

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Elena Montes-Cobos

Full Text Available Mineralocorticoid receptor (MR inactivation in mice results in early postnatal lethality. Therefore we generated mice in which MR expression can be silenced during adulthood by administration of doxycycline (Dox. Using a lentiviral approach, we obtained two lines of transgenic mice harboring a construct that allows for regulatable MR inactivation by RNAi and concomitant expression of eGFP. MR mRNA levels in heart and kidney of inducible MR knock-down mice were unaltered in the absence of Dox, confirming the tightness of the system. In contrast, two weeks after Dox administration MR expression was significantly diminished in a variety of tissues. In the kidney, this resulted in lower mRNA levels of selected target genes, which was accompanied by strongly increased serum aldosterone and plasma renin levels as well as by elevated sodium excretion. In the healthy heart, gene expression and the amount of collagen were unchanged despite MR levels being significantly reduced. After transverse aortic constriction, however, cardiac hypertrophy and progressive heart failure were attenuated by MR silencing, fibrosis was unaffected and mRNA levels of a subset of genes reduced. Taken together, we believe that this mouse model is a useful tool to investigate the role of the MR in pathophysiological processes.

A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8.

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Bouhy, Delphine; Juneja, Manisha; Katona, Istvan; Holmgren, Anne; Asselbergh, Bob; De Winter, Vicky; Hochepied, Tino; Goossens, Steven; Haigh, Jody J; Libert, Claude; Ceuterick-de Groote, Chantal; Irobi, Joy; Weis, Joachim; Timmerman, Vincent

2018-01-01

Mutations in the small heat shock protein B8 gene (HSPB8/HSP22) have been associated with distal hereditary motor neuropathy, Charcot-Marie-Tooth disease, and recently distal myopathy. It is so far not clear how mutant HSPB8 induces the neuronal and muscular phenotypes and if a common pathogenesis lies behind these diseases. Growing evidence points towards a role of HSPB8 in chaperone-associated autophagy, which has been shown to be a determinant for the clearance of poly-glutamine aggregates in neurodegenerative diseases but also for the maintenance of skeletal muscle myofibrils. To test this hypothesis and better dissect the pathomechanism of mutant HSPB8, we generated a new transgenic mouse model leading to the expression of the mutant protein (knock-in lines) or the loss-of-function (functional knock-out lines) of the endogenous protein Hspb8. While the homozygous knock-in mice developed motor deficits associated with degeneration of peripheral nerves and severe muscle atrophy corroborating patient data, homozygous knock-out mice had locomotor performances equivalent to those of wild-type animals. The distal skeletal muscles of the post-symptomatic homozygous knock-in displayed Z-disk disorganisation, granulofilamentous material accumulation along with Hspb8, αB-crystallin (HSPB5/CRYAB), and desmin aggregates. The presence of the aggregates correlated with reduced markers of effective autophagy. The sciatic nerve of the homozygous knock-in mice was characterized by low autophagy potential in pre-symptomatic and Hspb8 aggregates in post-symptomatic animals. On the other hand, the sciatic nerve of the homozygous knock-out mice presented a normal morphology and their distal muscle displayed accumulation of abnormal mitochondria but intact myofiber and Z-line organisation. Our data, therefore, suggest that toxic gain-of-function of mutant Hspb8 aggregates is a major contributor to the peripheral neuropathy and the myopathy. In addition, mutant Hspb8 induces

THE EFFECT OF WAIST CIRCUMFERENCES MORE THAN NORMAL ON THE INCIDENT OF CORONARY HEART DISEASE

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Pria Wahyu

2017-07-01

Full Text Available Introduction: Coronary heart disease is known as the most common disease that causes mortality in the world, one of the examination to identify the risks of coronary heart disease is measuring waist circumference. The purpose of this study was to identify correlation between large waist circumferences and the incident of coroner heart disease. Method: Design used in this study was analytic observational (retrospective with cross sectional approach. There were 63 respondents which sampling by simple random sampling. The independent variable was waist circumferences and the dependent variable was coronary heart disease. Data were collected by direct observation then analyzed by spearman correlation statistic test with significance level α≤0.05. Result: The result showed that waist circumferences more than normal had significant correlation with the incident of coronary heart disease (p=0.02. Analysis: It can be concluded that there was correlation between waist circumferences more than normal and the incident of coronary heart disease to the clients with coroner cardiac disease. Discussion: Earlier screening and detection is needed to prevent coronary heart disease.

Cardiovascular cast model fabrication and casting effectiveness evaluation in fetus with severe congenital heart disease or normal heart.

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Wang, Yu; Cao, Hai-yan; Xie, Ming-xing; He, Lin; Han, Wei; Hong, Liu; Peng, Yuan; Hu, Yun-fei; Song, Ben-cai; Wang, Jing; Wang, Bin; Deng, Cheng

2016-04-01

To investigate the application and effectiveness of vascular corrosion technique in preparing fetal cardiovascular cast models, 10 normal fetal heart specimens with other congenital disease (control group) and 18 specimens with severe congenital heart disease (case group) from induced abortions were enrolled in this study from March 2013 to June 2015 in our hospital. Cast models were prepared by injecting casting material into vascular lumen to demonstrate real geometries of fetal cardiovascular system. Casting effectiveness was analyzed in terms of local anatomic structures and different anatomical levels (including overall level, atrioventricular and great vascular system, left-sided and right-sided heart), as well as different trimesters of pregnancy. In our study, all specimens were successfully casted. Casting effectiveness analysis of local anatomic structures showed a mean score from 1.90±1.45 to 3.60±0.52, without significant differences between case and control groups in most local anatomic structures except left ventricle, which had a higher score in control group (P=0.027). Inter-group comparison of casting effectiveness in different anatomical levels showed no significant differences between the two groups. Intra-group comparison also revealed undifferentiated casting effectiveness between atrioventricular and great vascular system, or left-sided and right-sided heart in corresponding group. Third-trimester group had a significantly higher perfusion score in great vascular system than second-trimester group (P=0.046), while the other anatomical levels displayed no such difference. Vascular corrosion technique can be successfully used in fabrication of fetal cardiovascular cast model. It is also a reliable method to demonstrate three-dimensional anatomy of severe congenital heart disease and normal heart in fetus.

Knock-in mice harboring a Ca(2+) desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy.

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McConnell, Bradley K; Singh, Sonal; Fan, Qiying; Hernandez, Adriana; Portillo, Jesus P; Reiser, Peter J; Tikunova, Svetlana B

2015-01-01

The physiological consequences of aberrant Ca(2+) binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca(2+) sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca(2+) sensitivity of reconstituted thin filaments by increasing the rate of Ca(2+) dissociation. In addition, the D73N mutation drastically blunted the extent of Ca(2+) desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca(2+) sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was 12 weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction (EF) and fractional shortening (FS), were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to β-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM). In conclusion, our results suggest that decreasing Ca(2+) sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM.

Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock-in mice without or with Aβ accumulation.

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Tong, Leslie M; Djukic, Biljana; Arnold, Christine; Gillespie, Anna K; Yoon, Seo Yeon; Wang, Max M; Zhang, Olivia; Knoferle, Johanna; Rubenstein, John L R; Alvarez-Buylla, Arturo; Huang, Yadong

2014-07-16

Excitatory and inhibitory balance of neuronal network activity is essential for normal brain function and may be of particular importance to memory. Apolipoprotein (apo) E4 and amyloid-β (Aβ) peptides, two major players in Alzheimer's disease (AD), cause inhibitory interneuron impairments and aberrant neuronal activity in the hippocampal dentate gyrus in AD-related mouse models and humans, leading to learning and memory deficits. To determine whether replacing the lost or impaired interneurons rescues neuronal signaling and behavioral deficits, we transplanted embryonic interneuron progenitors into the hippocampal hilus of aged apoE4 knock-in mice without or with Aβ accumulation. In both conditions, the transplanted cells developed into mature interneurons, functionally integrated into the hippocampal circuitry, and restored normal learning and memory. Thus, restricted hilar transplantation of inhibitory interneurons restores normal cognitive function in two widely used AD-related mouse models, highlighting the importance of interneuron impairments in AD pathogenesis and the potential of cell replacement therapy for AD. More broadly, it demonstrates that excitatory and inhibitory balance are crucial for learning and memory, and suggests an avenue for investigating the processes of learning and memory and their alterations in healthy aging and diseases. Copyright © 2014 the authors 0270-6474/14/349506-10$15.00/0.

'Knock, and it shall be opened': knocking out and knocking in to reveal mechanisms of disease and novel therapies.

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Hacking, Douglas F

2008-12-01

Recent significant advances in molecular biology have generated genetically modified bacteria, yeast, nematodes, fruit flies, and fish. However, it is the genetic modification of mammalian model organisms, particularly the mouse, that has the greatest potential to shed light on human development, physiology and pathology in ways that have significant implications for neonatal and paediatric clinical practice. Here, we review some of the techniques for knocking out (inactivating), mutating and knocking in (inserting) selected genes that are important to neonatology and show how this research will lead both to a better understanding of disease and to novel therapies for infants and children.

Coronary heart disease patients transitioning to a normal life: perspectives and stages identified through a grounded theory approach.

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Najafi Ghezeljeh, Tahereh; Yadavar Nikravesh, Mansoureh; Emami, Azita

2014-02-01

To explore how Iranian patients with coronary heart disease experience their lives. Coronary heart disease is a leading cause of death in Iran and worldwide. Understanding qualitatively how patients experience the acute and postacute stages of this chronic condition is essential knowledge for minimising the negative consequences of coronary heart disease. Qualitative study using grounded theory for the data analysis. Data for this study were collected through individual qualitative interviews with 24 patients with coronary heart disease, conducted between January 2009 and January 2011. Patients with angina pectoris were selected for participation through purposive sampling, and sample size was determined by data saturation. Data analysis began with initial coding and continued with focused coding. Categories were determined, and the core category was subsequently developed and finalised. The main categories of the transition from acute phase to a modified or 'new normal' life were: (1) Loss of normal life. Experiencing emotions and consequences of illness; (2) Coming to terms. Using coping strategies; (3) Recreating normal life. Healthcare providers must correctly recognise the stages of transition patients navigate while coping with coronary heart disease to support and educate them appropriately throughout these stages. Patients with coronary heart disease lose their normal lives and must work towards recreating a revised life using coping strategies that enable them to come to terms with their situations. By understanding Iranian patients' experiences, healthcare providers and especially nurses can use the information to support and educate patients with coronary heart disease on how to more effectively deal with their illness and its consequences. © 2013 John Wiley & Sons Ltd.

Quantification of pulmonary thallium-201 activity after upright exercise in normal persons: importance of peak heart rate and propranolol usage in defining normal values

International Nuclear Information System (INIS)

Brown, K.A.; Boucher, C.A.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

1984-01-01

Fifty-nine normal patients (34 angiographically normal and 25 clinically normal by Bayesian analysis) underwent thallium-201 imaging after maximal upright exercise. Lung activity was quantitated relative to myocardial activity and a lung/myocardial activity ratio was determined for each patient. Stepwise regression analysis was then used to examine the influence of patient clinical characteristics and exercise variables on the lung/myocardium ratio. Peak heart rate during exercise and propranolol usage both showed significant negative regression coefficients (p less than 0.001). No other patient data showed a significant relation. Using the regression equation and the estimated variance, a 95% confidence level upper limit of normal could be determined for a give peak heart rate and propranolol status. Sixty-one other patients were studied to validate the predicted upper limits of normal based on this model. None of the 27 patients without coronary artery disease had an elevated lung/myocardial ratio, compared with 1 of 8 with 1-vessel disease (difference not significant), 6 of 14 with 2-vessel disease (p less than 0.005), and 6 of 12 with 3-vessel disease (p less than 0.0001). Thus, lung activity on upright exercise thallium-201 studies can be quantitated relative to myocardial activity, and is inversely related to peak heart rate and propranolol use. Use of a regression analysis allows determination of a 95% confidence upper limit of normal to be anticipated in an individual patient

3D imaging of the mitochondrial redox state of rat hearts under normal and fasting conditions

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He N. Xu

2014-03-01

Full Text Available The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo. Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD+ couple acting as a central electron carrier. We employed the Chance redox scanner — the low-temperature fluorescence scanner to image the three-dimensional (3D spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH (p = 0.038. No significant change in Fp was found (p = 0.4. The NADH/Fp ratio decreased with a marginal p value (0.076. The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the

3D IMAGING OF THE MITOCHONDRIAL REDOX STATE OF RAT HEARTS UNDER NORMAL AND FASTING CONDITIONS.

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Xu, He N; Zhou, Rong; Moon, Lily; Feng, Min; Li, Lin Z

2014-03-01

The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo . Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD + couple acting as a central electron carrier. We employed the Chance redox scanner - the low-temperature fluorescence scanner to image the three-dimensional (3D) spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD)) and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH ( p = 0.038). No significant change in Fp was found ( p = 0.4). The NADH/Fp ratio decreased with a marginal p value (0.076). The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the feasibility of 3D

Effect of Timing and Location of Hotspot on Super Knock during Pre-ignition

KAUST Repository

Jaasim, Mohammed

2017-03-28

Pre-ignition in SI engine is a critical issue that needs addressing as it may lead to super knock event. It is widely accepted that pre-ignition event emanates from hot spot(s) that can be anywhere inside the combustion chamber. The location and timing of hotspot is expected to influence the knock intensity from a pre-ignition event. In this study, we study the effect of location and timing of hot spot inside the combustion chamber using numerical simulations. The simulation is performed using a three-dimensional computational fluid dynamics (CFD) code, CONVERGE™. We simulate 3-D engine geometry coupled with chemistry, turbulence and moving structures (valves, piston). G-equation model for flame tracking coupled with multi-zone model is utilized to capture auto-ignition (knock) and solve gas phase kinetics. A parametric study on the effect of hot spot timing and location inside the combustion chamber is performed. The hot spot timing considered are -180 CAD, -90 CAD and -30 CAD and the locations of the hot spots are in the center and two edges of the piston surfaces. Simulation results for normal combustion cycle are validated against the experimental data. The simulation results show great sensitivity to the hot spot timing, and the influence of local temperature gradient is noted to be significant. In case of early hot spot timing of -180 CAD, the pre-ignition event did not lead to super knock. Nevertheless, at late hot spot timing, super knock was realized. On the other hand, the effect of hot spot location on pre-ignition event depends on the geometry of the combustion chamber.

Computational singular perturbation analysis of super-knock in SI engines

KAUST Repository

Jaasim, Mohammed

2018-04-02

Pre-ignition engine cycles leading to super-knock were simulated with a 48 species skeletal iso-octane mechanism to identify the dominant reaction pathways that are present in super-knock. To mimic pre-ignition, a deflagration front was generated via a hot spot that is placed over the piston at close proximity to the end-wall. Computational singular perturbation (CSP) was used to analyze the chemical dynamics at various in-cylinder locations: a point at the center of the cylinder where the deflagration front consumes the air/fuel mixture and two points located at 3 mm from the end-wall where super-knock and mild knock occur. The CSP analysis of the point at the center of the cylinder reveals weak two-stage ignition-like dynamics with a short second stage. At the other points, a pronounced two-stage ignition is displayed with a long second stage. A distinct contribution of formaldehyde (CHO) at the second stage of ignition that adds to fast explosive modes in the super-knock points is not observed in the point at the center. A comparison between knock and super-knock analysis indicates that a similar set of reactions is responsible for the abnormal behavior but the fast explosive time scales are comparatively slower for knock, indicating lower reactivity, which results in the reduced intensity of knock. The analyzed results decoded important reactions responsible for the occurrence of super-knock.

Catecholaminergic polymorphic ventricular tachycardia. An important diagnosis in children with syncope and normal heart

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Luiz Roberto Leite

2001-01-01

Full Text Available Syncope in children is primarily related to vagal hyperreactivity, but ventricular tachycardia (VT way rarely be seen. Catecholaminergic polymorphic VT is a rare entity that can occur in children without heart disease and with a normal QT interval, which may cause syncope and sudden cardiac death. In this report, we describe the clinical features, treatment, and clinical follow-up of three children with syncope associated with physical effort or emotion and cathecolaminergic polymorphic VT. Symptoms were controlled with beta-blockers, but one patient died suddenly in the fourth year of follow-up. Despite the rare occurrence, catecholaminergic polymorphic VT is an important cause of syncope and sudden death in children with no identified heart disease and normal QT interval.

Pressure indication during knocking conditions; Druckindizierung bei klopfender Verbrennung

Energy Technology Data Exchange (ETDEWEB)

Bertola, A.; Stadler, J.; Walter, T.; Wolfer, P. [Kistler Instrumente AG Winterthur (Switzerland); Gossweiler, C. [Fachhochschule Nordwestschweiz ITFE (Switzerland); Rothe, M. [Karlsruhe Univ. (Germany). Inst. fuer Kolbenmaschinen

2006-07-01

Depending on its frequency and intensity, knocking combustion can cause engine damage due to excessive thermal or mechanical stress on components. During knocking combustion, the cylinder pressure signal is overlaid with high-frequency pressure oscillations. Reliable detection of the knock timing and quantification of the knock intensity based on local measurement of the cylinder pressure demand for particular care, especially when it comes to selecting and adapting the sensor technology and also during the evaluation process using customary knock analysis methods. This publication examines various types of cylinder pressure sensors, how they are installed in the combustion chamber, the effect of sensor positioning and assesses them with regard to accuracy. Finally, on the basis of the test results, recommendations are given for selecting sensors and adapting them within the combustion chamber. A crucial factor for pressure measurement during knocking combustion is the sensor position within the combustion chamber. The sensor type is of secondary importance; at most, cavities between the combustion chamber and the sensor may influence the measuring signal. To assess the sensitivity of the knock evaluation algorithms to various mounting positions and sensor types, it is advisable to carry out comparative measurements between different sensor positions and the measuring spark plug. (orig.)

Theoretical analysis of knock-out release of fission products from nuclear fuels

International Nuclear Information System (INIS)

Yamagishi, S.

1975-01-01

The knock-out release of fission products is studied theoretically. The general equations of knock-out release are derived, assuming that a fission fragment passing through the surface of nuclear fuels knocks out a local region of the surface with an effective thickness and an effective cross-sectional area. Using these equations, the knock-out release of fission gases is calculated for various cases. The conditions under which the knock-out coefficients (the average number of uranium atoms knocked out by one fission fragment) is obtainable are clarified by experiments on the knock-out release of fission gases. A method of determining the effective thickness and the effective cross-sectional area of a knock-out region is proposed. (Auth.)

Efficient gene knock-out and knock-in with transgenic Cas9 in Drosophila.

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Xue, Zhaoyu; Ren, Mengda; Wu, Menghua; Dai, Junbiao; Rong, Yikang S; Gao, Guanjun

2014-03-21

Bacterial Cas9 nuclease induces site-specific DNA breaks using small gRNA as guides. Cas9 has been successfully introduced into Drosophila for genome editing. Here, we improve the versatility of this method by developing a transgenic system that expresses Cas9 in the Drosophila germline. Using this system, we induced inheritable knock-out mutations by injecting only the gRNA into embryos, achieved highly efficient mutagenesis by expressing gRNA from the promoter of a novel non-coding RNA gene, and recovered homologous recombination-based knock-in of a fluorescent marker at a rate of 4.5% by co-injecting gRNA with a circular DNA donor. Copyright © 2014 Xue et al.

Normal cardiac diameters in cine-MRI of the heart

International Nuclear Information System (INIS)

Hergan, K.; Schuster, A.; Mair, M.; Burger, R.; Toepker, M.

2004-01-01

Purpose: To measure the normal diameters of cardiac cavities in standard cardiac views using cine MRI. Materials and Methods: Fifty-six volunteers were examined (27 male, 29 female) on a 1.5 T MR unit with ECG-triggered single shot free precision (SSFP) cine MR sequences and parallel image acquisition. Standardized echocardiographic planes were used to depict the heart of all volunteers (short axis, 4-chamber view, left and right 2-chamber views). The different diameters of the cardiac cavities were measured using a fixed protocol. Results: For the estimation of ventricular dilatation, the important female/male cross diameters of the left ventricle are 45.2±3.4/51.6±4.6 mm diastolic and 30.5±3.5/33.8±3.6 mm systolic, and of the right ventricle 30.7±3.8/37.1±5.9 mm diastolic and 22.3±3.8/28.1±4.4 mm systolic. For the determination of a left ventricular hypertrophy, relevant septal wall thickness measured in the short axis of the left ventricle of female/male volunteers are 8.0±1.0/9.9±1.2 mm diastolic and 10.9±1.4/13.6±1.9 mm systolic. The measured normal values of male volunteers were generally higher than those of female volunteers. The thickness of the ventricular septum correlated well when measured in the short axis and 4-chamber view. When measured in the 4-chamber view, the longitudinal diameter of the ventricles had a higher value in diastole and a lower value in systole, compared to the 2-chamber views of the right and left cardiac cavities. The atrial longitudinal diameters were higher in the 4-chamber view compared to the 2-chamber views, without any difference in systole or diastole. Conclusion: Diameters of cardiac cavities are easily and quickly measured. Using the tables with the normal values published here, it is simple to estimate an abnormal size of the heart. (orig.)

Influence of peak exercise heart rate on normal thallium-201 myocardial clearance

International Nuclear Information System (INIS)

Kaul, S.; Chesler, D.A.; Pohost, G.M.; Strauss, H.W.; Okada, R.D.; Boucher, C.A.

1986-01-01

Measurement of myocardial clearance rates between initial and delayed images is a major justification for adding computer quantification to the interpretation of exercise 201 TI images. To clarify the range of normal thallium clearance and its relationship to the level of exercise achieved, exercise thallium images in 89 normal subjects were analyzed: 45 asymptomatic subjects with less than 1% probability of coronary artery disease (CAD) (Group I), and 44 patients with chest pain found to have no significant CAD on angiography (Group II). Mean initial regional thallium uptake was similar in the two groups, but myocardial thallium clearance (mean +/- 1 s.d.) was slower in Group II, expressed as a longer half-life in the myocardium (8.2 +/- 7.6 hr compared with 3.4 +/- 0.7 hr p less than 0.001). Analysis of variance using ten clinical and exercise variables as covariates showed that the slower clearance in Group II was related to a lower peak exercise heart rate (HR) (154 +/- 27 compared with 183 +/- 11, respectively, p less than 0.001). By linear regression analysis, a decrease in peak HR of 1 beat/min was associated with a slower thallium clearance (longer half-life) of 0.05 hr. Using this formula, the clearance value in each patient was then corrected for peak exercise heart rate by decreasing measured clearance by 0.05 hr multiplied by the amount peak exercise heart rate which was below 183 (the mean value in Group I). There were no differences in the corrected clearance between the two groups. We conclude that thallium myocardial clearance after exercise is related in part to factors other than the presence of CAD, being slower when peak exercise HR is lower. Therefore, thallium clearance rates alone uncorrected for peak exercise heart rate should be used with caution when diagnosing CAD

Oral triiodothyronine normalizes triiodothyronine levels after surgery for pediatric congenital heart disease*.

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Marwali, Eva M; Boom, Cindy E; Sakidjan, Indriwanto; Santoso, Anwar; Fakhri, Dicky; Kartini, Ay; Kekalih, Aria; Schwartz, Steven M; Haas, Nikolaus A

2013-09-01

This study was conducted to determine if oral triiodothyronine supplementation could prevent the decrease of serum triiodothyronine levels that commonly occurs after cardiopulmonary bypass for pediatric congenital heart surgery. Secondary objectives included identifying any significant adverse effects of oral triiodothyronine supplementation, including any effects on the thyroid/pituitary axis. Randomized, placebo-controlled, doubleblind clinical trial Operating room and ICU. Infants and children younger than 2 years of age undergoing congenital heart surgery using cardiopulmonary bypass (n = 43). Subjects were assigned to placebo (n = 15, group A) or one of two treatment groups: a low-dose group (group B, n = 14, 0.5 mcg/kg triiodothyronine orally every 24 hr for 3 d) or a high-dose group (group C, n = 14, 0.5 mcg/kg triiodothyronine orally every 12 hr for 3 d). Thyroid hormone, including total and free triiodothyronine levels at predetermined time points, potential side effects indicating hyperthyroidism, indicators of the thyroid-pituitary axis, and clinical endpoints. Oral triiodothyronine supplementation twice-daily maintained serum triiodothyronine levels within normal limits in group C, whereas serum levels progressively declined in groups A and B. A statistically significant difference in triiodothyronine levels between the treatment groups occurred between 18 and 36 hours post cross-clamp release, with the largest difference in serum levels between group C and group A noted at 36 hours post cross-clamp release (total triiodothyronine, 0.71 ± 0.15 [0.34-1.08] ng/mL [p triiodothyronine, 2.56 ± 0.49 [1.33-3.79] pg/mL [p triiodothyronine supplementation at a dose of 0.5 mcg/kg every 12 hours for 3 days can maintain total and free triiodothyronine levels within normal limits after open-heart surgery using cardiopulmonary bypass for congenital heart disease.

Ionization in the Knock Zone of an Internal-combustion Engine

Science.gov (United States)

Hasting, Charles E

1940-01-01

The ionization in the knock zone of an internal-combustion engine was investigated. A suspected correlation between the intensity of knock and the degree of ionization was verified and an oscillation in the degree of ionization corresponding in frequency to the knock vibrations in the cylinder pressure was observed.

I'll knock you when I'm ready

DEFF Research Database (Denmark)

Rasmussen, Majken Kirkegaard; Krogh, Peter; Lehoux, Natalie

2012-01-01

, and the qualities of suggestive interactions that mediate communication. We introduce Knock-Knock as a novel, shape-changing communication medium, and use it as a rhetorical tool to reflect upon the notion of media richness. In doing so, we highlight the value of meaning and language creation that suggestive...

Surface sensitivity of nuclear-knock-out form factors

International Nuclear Information System (INIS)

Fratamico, G.

1984-01-01

A numerical calculation has been performed to investigate the sensitivity of nuclear-knock-out form factors to nuclear-surface behaviour of bound-state wave functions. The result of our investigation suggests that one can extract the bound-state behaviour at the surface from experimental information on nuclear-knock-out form factors

Proton knock-out in Hall A

International Nuclear Information System (INIS)

Jager, K. de

2003-01-01

Proton knock-out is studied in a broad program in Hall A at Jefferson Lab. The first experiment performed in Hall A studied the 16 O(e,e'p) reaction. Since then proton knock-out experiments have studied a variety of aspects of that reaction, from single-nucleon properties to its mechanism, such as final-state interactions and two-body currents, in nuclei from 2 H to 16 O. In this review the accomplishments of this program will be summarized and an outlook given of expected future results. (orig.)

Knock investigation by flame and radical species detection in spark ignition engine for different fuels

International Nuclear Information System (INIS)

Merola, Simona S.; Vaglieco, Bianca M.

2007-01-01

The present paper aims to evaluate the phenomena of normal combustion and knocking in a single cylinder, ported fuel injection, four-stroke spark-ignition engine with a four-valve production head. All the measurements were realized in an optically accessible engine equipped with a wide quartz window in the bottom of the chamber. The study was carried out using optical techniques based on flame natural emission imaging and spectroscopy from UV to visible. Radical species such as OH and HCO were detected and correlated to the onset and the duration of knock and presence of hot-spots in end-gas. Measurements were carried out at 1000 rpm with wide-open throttle and stoichiometric mixture. Pure iso-octane, suitable mixtures of iso-octane and n-heptane and commercial gasoline were used

Prediction of knock limited operating conditions of a natural gas engine

International Nuclear Information System (INIS)

Soylu, Seref

2005-01-01

Computer models of engine processes are valuable tools for predicting and analyzing engine performance and allow exploration of many engine design alternatives in an inexpensive fashion. In the present work, a zero-dimensional, two zone thermodynamic model was used to determine the knock limited operating conditions of a natural gas engine. Experimentally based burning rate models were used for flame initiation and propagation calculations. A knock model was incorporated with the zero-dimensional model. Comparison of the measured and calculated cylinder pressure data indicated that the model is able to match the measured cylinder pressure data with less than 8% error in magnitudes if the computations are started at the experimental spark timing. The knock predictions agreed with the measurements also. With the established knock model, it is possible not only to investigate whether knock is observed with changing operating and design parameters, but also to evaluate their effects on the maximum possible knock intensity

Clinical Characteristics and Findings of 99mTc-MIBI Heart SPECT in Patients with Acute Myocardial Infarction with Normal Coronary Arteriography

International Nuclear Information System (INIS)

Park, Myung Jae; Choi, Tae Youl; Kim, Deong Yoon; Kang, Heung Sun; Choue, Chung Whee; Kim, Kwon Sam; Kim, Kwang Won; Kim, Myung Shick; Song, Jung Sang; Bae, Jong Hoa

1993-01-01

Among 64 patients with acute myocardial infarction who underwent coronary angiography, 7 patients (10.9%)showed normal coronary artery. Six patients were men and 1 patient was female. The mean age of patients were 31.1 ± 3.9 years. Among the risk factors of coronary heart disease, smoking was most probable factor in patients with acute myocardial infarction with normal coronary angiography. 99m Tc-MIBI heart SPECT performed 5 of 7 patients and showed that it could be used in diagnosis, localization, extent of infarct area in patients with acute myocardial infarction with normal coronary angiography. But follow up 99m Tc-MIBI heart SPECT study will be needed to define the ability of myocardial viability in this patients.

A method of estimating the knock rating of hydrocarbon fuel blend

Science.gov (United States)

Sanders, Newell D

1943-01-01

The usefulness of the knock ratings of pure hydrocarbon compounds would be increased if some reliable method of calculating the knock ratings of fuel blends was known. The purpose of this study was to investigate the possibility of developing a method of predicting the knock ratings of fuel blends.

Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice.

Science.gov (United States)

Beccano-Kelly, Dayne A; Kuhlmann, Naila; Tatarnikov, Igor; Volta, Mattia; Munsie, Lise N; Chou, Patrick; Cao, Li-Ping; Han, Heather; Tapia, Lucia; Farrer, Matthew J; Milnerwood, Austen J

2014-01-01

Mutations in Leucine-Rich Repeat Kinase-2 (LRRK2) result in familial Parkinson's disease and the G2019S mutation alone accounts for up to 30% in some ethnicities. Despite this, the function of LRRK2 is largely undetermined although evidence suggests roles in phosphorylation, protein interactions, autophagy and endocytosis. Emerging reports link loss of LRRK2 to altered synaptic transmission, but the effects of the G2019S mutation upon synaptic release in mammalian neurons are unknown. To assess wild type and mutant LRRK2 in established neuronal networks, we conducted immunocytochemical, electrophysiological and biochemical characterization of >3 week old cortical cultures of LRRK2 knock-out, wild-type overexpressing and G2019S knock-in mice. Synaptic release and synapse numbers were grossly normal in LRRK2 knock-out cells, but discretely reduced glutamatergic activity and reduced synaptic protein levels were observed. Conversely, synapse density was modestly but significantly increased in wild-type LRRK2 overexpressing cultures although event frequency was not. In knock-in cultures, glutamate release was markedly elevated, in the absence of any change to synapse density, indicating that physiological levels of G2019S LRRK2 elevate probability of release. Several pre-synaptic regulatory proteins shown by others to interact with LRRK2 were expressed at normal levels in knock-in cultures; however, synapsin 1 phosphorylation was significantly reduced. Thus, perturbations to the pre-synaptic release machinery and elevated synaptic transmission are early neuronal effects of LRRK2 G2019S. Furthermore, the comparison of knock-in and overexpressing cultures suggests that one copy of the G2019S mutation has a more pronounced effect than an ~3-fold increase in LRRK2 protein. Mutant-induced increases in transmission may convey additional stressors to neuronal physiology that may eventually contribute to the pathogenesis of Parkinson's disease.

[Estimation of the atrioventricular time interval by pulse Doppler in the normal fetal heart].

Science.gov (United States)

Hamela-Olkowska, Anita; Dangel, Joanna

2009-08-01

To assess normative values of the fetal atrioventricular (AV) time interval by pulse-wave Doppler methods on 5-chamber view. Fetal echocardiography exams were performed using Acuson Sequoia 512 in 140 singleton fetuses at 18 to 40 weeks of gestation with sinus rhythm and normal cardiac and extracardiac anatomy. Pulsed Doppler derived AV intervals were measured from left ventricular inflow/outflow view using transabdominal convex 3.5-6 MHz probe. The values of AV time interval ranged from 100 to 150 ms (mean 123 +/- 11.2). The AV interval was negatively correlated with the heart rhythm (page of gestation (p=0.007). However, in the same subgroup of the fetal heart rate there was no relation between AV intervals and gestational age. Therefore, the AV intervals showed only the heart rate dependence. The 95th percentiles of AV intervals according to FHR ranged from 135 to 148 ms. 1. The AV interval duration was negatively correlated with the heart rhythm. 2. Measurement of AV time interval is easy to perform and has a good reproducibility. It may be used for the fetal heart block screening in anti-Ro and anti-La positive pregnancies. 3. Normative values established in the study may help obstetricians in assessing fetal abnormalities of the AV conduction.

Multivariate Normal Tissue Complication Probability Modeling of Heart Valve Dysfunction in Hodgkin Lymphoma Survivors

International Nuclear Information System (INIS)

Cella, Laura; Liuzzi, Raffaele; Conson, Manuel; D’Avino, Vittoria; Salvatore, Marco; Pacelli, Roberto

2013-01-01

Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced asymptomatic heart valvular defects (RVD). Methods and Materials: Fifty-six patients treated with sequential chemoradiation therapy for Hodgkin lymphoma (HL) were retrospectively reviewed for RVD events. Clinical information along with whole heart, cardiac chambers, and lung dose distribution parameters was collected, and the correlations to RVD were analyzed by means of Spearman's rank correlation coefficient (Rs). For the selection of the model order and parameters for NTCP modeling, a multivariate logistic regression method using resampling techniques (bootstrapping) was applied. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: When we analyzed the whole heart, a 3-variable NTCP model including the maximum dose, whole heart volume, and lung volume was shown to be the optimal predictive model for RVD (Rs = 0.573, P<.001, AUC = 0.83). When we analyzed the cardiac chambers individually, for the left atrium and for the left ventricle, an NTCP model based on 3 variables including the percentage volume exceeding 30 Gy (V30), cardiac chamber volume, and lung volume was selected as the most predictive model (Rs = 0.539, P<.001, AUC = 0.83; and Rs = 0.557, P<.001, AUC = 0.82, respectively). The NTCP values increase as heart maximum dose or cardiac chambers V30 increase. They also increase with larger volumes of the heart or cardiac chambers and decrease when lung volume is larger. Conclusions: We propose logistic NTCP models for RVD considering not only heart irradiation dose but also the combined effects of lung and heart volumes. Our study establishes the statistical evidence of the indirect effect of lung size on radio-induced heart toxicity

Gene cassette knock-in in mammalian cells and zygotes by enhanced MMEJ.

Science.gov (United States)

Aida, Tomomi; Nakade, Shota; Sakuma, Tetsushi; Izu, Yayoi; Oishi, Ayu; Mochida, Keiji; Ishikubo, Harumi; Usami, Takako; Aizawa, Hidenori; Yamamoto, Takashi; Tanaka, Kohichi

2016-11-28

Although CRISPR/Cas enables one-step gene cassette knock-in, assembling targeting vectors containing long homology arms is a laborious process for high-throughput knock-in. We recently developed the CRISPR/Cas-based precise integration into the target chromosome (PITCh) system for a gene cassette knock-in without long homology arms mediated by microhomology-mediated end-joining. Here, we identified exonuclease 1 (Exo1) as an enhancer for PITCh in human cells. By combining the Exo1 and PITCh-directed donor vectors, we achieved convenient one-step knock-in of gene cassettes and floxed allele both in human cells and mouse zygotes. Our results provide a technical platform for high-throughput knock-in.

A neuroanatomical and physiological study of the non-image forming visual system of the cone-rod homeobox gene (Crx) knock out mouse

DEFF Research Database (Denmark)

Rovsing, Louise; Rath, Martin F; Lund-Andersen, Casper

2010-01-01

The anatomy and physiology of the non-image forming visual system was investigated in a visually blind cone-rod homeobox gene (Crx) knock-out mouse (Crx(-)(/)(-)), which lacks the outer segments of the photoreceptors. We show that the suprachiasmatic nuclei (SCN) in the Crx(-/-) mouse exhibit...... melanopsin neurons or the SCN may be necessary for a normal function of the non-image forming system of the mouse. However, a change in the SCN of the Crx(-/-) mouse might also explain the observed circadian differences between the knock out mouse and wild type mouse....

A Knock-in Reporter for a Novel AR-Targeted Therapy

Science.gov (United States)

2016-05-01

AWARD NUMBER: W81XWH-15-1-0049 TITLE: A Knock -in Reporter for a Novel AR-Targeted Therapy PRINCIPAL INVESTIGATOR: Chunhong Yan, Ph.D...5a. CONTRACT NUMBER A Knock -in Reporter for a Novel AR-Targeted Therapy 5b. GRANT NUMBER W81XWH-15-1-0049 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...enhancer. While the knock -in reporter is expected to faithfully reproduce chemical responses of the endogenous AR gene, we carried out a pilot screen

Eliminating graphs by means of parallel knock-out schemes

NARCIS (Netherlands)

Broersma, H.J.; Fomin, F.V.; Královic, R.; Woeginger, G.J.

2007-01-01

In 1997 Lampert and Slater introduced parallel knock-out schemes, an iterative process on graphs that goes through several rounds. In each round of this process, every vertex eliminates exactly one of its neighbors. The parallel knock-out number of a graph is the minimum number of rounds after which

Eliminating graphs by means of parallel knock-out schemes

NARCIS (Netherlands)

Broersma, Haitze J.; Fomin, F.V.; Královič, R.; Woeginger, Gerhard

In 1997 Lampert and Slater introduced parallel knock-out schemes, an iterative process on graphs that goes through several rounds. In each round of this process, every vertex eliminates exactly one of its neighbors. The parallel knock-out number of a graph is the minimum number of rounds after which

A predictive model for knock onset in spark-ignition engines with cooled EGR

International Nuclear Information System (INIS)

Chen, Longhua; Li, Tie; Yin, Tao; Zheng, Bin

2014-01-01

Highlights: • Ratio of specific heats should be used as variable in development of knock model. • Increases in EGR or excess air ratio lead to increases in the ratio of specific heats. • The widely-used Douaud–Eyzat correlation fails to predict the knock onset when increasing EGR. • The newly developed model including p, T, EGR and λ as variables predicts the knock onset accurately. • Effect of temperature at intake valve closure on the predicted knock onset is relatively small. - Abstract: A predictive knock model is crucial for one dimensional (1-D) engine cycle simulation that has been proven to be a powerful tool in both optimization of the conceptual design and reduction of calibration efforts in development of spark-ignition (SI) engines. With application of advanced technologies such as exhaust gas recirculation (EGR) in modern SI engines, update of knock model is needed to give an acceptable prediction of knock onset. In this study, bench tests of a turbocharged gasoline SI engine with cooled EGR system operated under knocking conditions were conducted, the cylinder pressure traces were analyzed by the band-pass filtering technique, and the crank angle of knock onset was determined by the signal energy ratio (SER) and image processing method. A knock model considering multi-variable effects including pressure, temperature, EGR ratio and excess air ratio (λ) is formulated and calibrated with the experimental data using the multi-island genetic algorithm (GA). The calculation method of the end gas temperature, the impacts of the ratio of specific heats as well as the temperature at the intake valve closure on the end gas temperature are discussed. The performance of the new model is compared with the widely-used phenomenological knock models such as Douaud–Eyzat model and Hoepke model. While the widely-used knock models fail to give acceptable predictions when increasing EGR with fuel enrichment operations, the new model predicts the knock

The knock study of methanol fuel based on multi-dimensional simulation analysis

International Nuclear Information System (INIS)

Zhen, Xudong; Liu, Daming; Wang, Yang

2017-01-01

Methanol is an alternative fuel, and considered to be one of the most favorable fuels for engines. In this study, knocking combustion in a developed ORCEM (optical rapid compression and expansion machine) is studied based on the multi-dimensional simulation analysis. The LES (large-eddy simulation) models coupled with methanol chemical reaction kinetics (contains 21-species and 84-elementary reactions) is adopted to study knocking combustion. The results showed that the end-gas auto-ignition first occurred in the position near the chamber wall because of the higher temperature and pressure. The H_2O_2 species could be a good flame front indicator. OH radicals played the major role, and the HCO radicals almost could be ignored during knocking combustion. The HCO radicals generated little, so its concentration during knocking combustion almost may be ignored. The mean reaction intensity results of CH_2O, OH, H_2O_2, and CO were higher than others during knocking combustion. Finally, this paper put forward some new suggestions on the weakness in the knocking combustion researches of methanol fuel. - Highlights: • Knocking combustion of methanol was studied in a developed ORCEM. • The LES coupled with detailed chemical kinetics was adopted to simulation study. • The end-gas auto-ignition first occurred in the place near the chamber wall. • OH radical was the predominant species during knocking combustion. • The H_2O_2 species could be a good flame front indicator.

Closed loop statistical performance analysis of N-K knock controllers

Science.gov (United States)

Peyton Jones, James C.; Shayestehmanesh, Saeed; Frey, Jesse

2017-09-01

The closed loop performance of engine knock controllers cannot be rigorously assessed from single experiments or simulations because knock behaves as a random process and therefore the response belongs to a random distribution also. In this work a new method is proposed for computing the distributions and expected values of the closed loop response, both in steady state and in response to disturbances. The method takes as its input the control law, and the knock propensity characteristic of the engine which is mapped from open loop steady state tests. The method is applicable to the 'n-k' class of knock controllers in which the control action is a function only of the number of cycles n since the last control move, and the number k of knock events that have occurred in this time. A Cumulative Summation (CumSum) based controller falls within this category, and the method is used to investigate the performance of the controller in a deeper and more rigorous way than has previously been possible. The results are validated using onerous Monte Carlo simulations, which confirm both the validity of the method and its high computational efficiency.

Knock probability estimation through an in-cylinder temperature model with exogenous noise

Science.gov (United States)

Bares, P.; Selmanaj, D.; Guardiola, C.; Onder, C.

2018-01-01

This paper presents a new knock model which combines a deterministic knock model based on the in-cylinder temperature and an exogenous noise disturbing this temperature. The autoignition of the end-gas is modelled by an Arrhenius-like function and the knock probability is estimated by propagating a virtual error probability distribution. Results show that the random nature of knock can be explained by uncertainties at the in-cylinder temperature estimation. The model only has one parameter for calibration and thus can be easily adapted online. In order to reduce the measurement uncertainties associated with the air mass flow sensor, the trapped mass is derived from the in-cylinder pressure resonance, which improves the knock probability estimation and reduces the number of sensors needed for the model. A four stroke SI engine was used for model validation. By varying the intake temperature, the engine speed, the injected fuel mass, and the spark advance, specific tests were conducted, which furnished data with various knock intensities and probabilities. The new model is able to predict the knock probability within a sufficient range at various operating conditions. The trapped mass obtained by the acoustical model was compared in steady conditions by using a fuel balance and a lambda sensor and differences below 1 % were found.

Knock Prediction Using a Simple Model for Ignition Delay

KAUST Repository

Kalghatgi, Gautam

2016-04-05

An earlier paper has shown the ability to predict the phasing of knock onset in a gasoline PFI engine using a simple ignition delay equation for an appropriate surrogate fuel made up of toluene and PRF (TPRF). The applicability of this approach is confirmed in this paper in a different engine using five different fuels of differing RON, sensitivity, and composition - including ethanol blends. An Arrhenius type equation with a pressure correction for ignition delay can be found from interpolation of previously published data for any gasoline if its RON and sensitivity are known. Then, if the pressure and temperature in the unburned gas can be estimated or measured, the Livengood-Wu integral can be estimated as a function of crank angle to predict the occurrence of knock. Experiments in a single cylinder DISI engine over a wide operating range confirm that this simple approach can predict knock very accurately. The data presented should enable engineers to study knock or other auto-ignition phenomena e.g. in premixed compression ignition (PCI) engines without explicit chemical kinetic calculations. © Copyright 2016 SAE International.

Optimized knock-in of point mutations in zebrafish using CRISPR/Cas9.

Science.gov (United States)

Prykhozhij, Sergey V; Fuller, Charlotte; Steele, Shelby L; Veinotte, Chansey J; Razaghi, Babak; Robitaille, Johane M; McMaster, Christopher R; Shlien, Adam; Malkin, David; Berman, Jason N

2018-06-14

We have optimized point mutation knock-ins into zebrafish genomic sites using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 reagents and single-stranded oligodeoxynucleotides. The efficiency of knock-ins was assessed by a novel application of allele-specific polymerase chain reaction and confirmed by high-throughput sequencing. Anti-sense asymmetric oligo design was found to be the most successful optimization strategy. However, cut site proximity to the mutation and phosphorothioate oligo modifications also greatly improved knock-in efficiency. A previously unrecognized risk of off-target trans knock-ins was identified that we obviated through the development of a workflow for correct knock-in detection. Together these strategies greatly facilitate the study of human genetic diseases in zebrafish, with additional applicability to enhance CRISPR-based approaches in other animal model systems.

A Photographic Study of Combustion and Knock in a Spark-Ignition Engine

Science.gov (United States)

Rothrock, A M; Spencer, R C

1938-01-01

Report presents the results of a photographic study of the combustion in a spark-ignition engine using both Schlieren and flame photographs taken at high rates of speed. Although shock waves are present after knock occurs, there was no evidence of any type of sonic or supersonic compression waves existing in the combustion gases prior to the occurrence of knock. Artificially induced shock waves in the engine did not in themselves cause knock. The photographs also indicate that, although auto-ignition ahead of the flame front may occur in conjunction with knock, it is not necessary for the occurrence of knock. There is also evidence that the reaction is not completed in the flame front but continues for some time after the flame front has passed through the charge.

Characterization of the first knock-out aldh7a1 zebrafish model for pyridoxine-dependent epilepsy using CRISPR-Cas9 technology.

Science.gov (United States)

Zabinyakov, Nikita; Bullivant, Garrett; Cao, Feng; Fernandez Ojeda, Matilde; Jia, Zheng Ping; Wen, Xiao-Yan; Dowling, James J; Salomons, Gajja S; Mercimek-Andrews, Saadet

2017-01-01

Pyridoxine dependent epilepsy (PDE) is caused by likely pathogenic variants in ALDH7A1 (PDE-ALDH7A1) and inherited autosomal recessively. Neurotoxic alpha-amino adipic semialdehyde (alpha-AASA), piperideine 6-carboxylate and pipecolic acid accumulate in body fluids. Neonatal or infantile onset seizures refractory to anti-epileptic medications are clinical features. Treatment with pyridoxine, arginine and lysine-restricted diet does not normalize neurodevelopmental outcome or accumulation of neurotoxic metabolites. There is no animal model for high throughput drug screening. For this reason, we developed and characterized the first knock-out aldh7a1 zebrafish model using CRISPR-Cas9 technology. Zebrafish aldh7a1 mutants were generated by using a vector free method of CRISPR-Cas9 mutagenesis. Genotype analysis of aldh7a1 knock-out zebrafish was performed by high resolution melt analysis, direct sequencing and QIAxcel system. Electroencephalogram was performed. Alpha-AASA, piperideine 6-carboxylate and pipecolic acid, were measured by liquid chromatography-tandem mass spectrometry. Our knock-out aldh7a1 zebrafish has homozygous 5 base pair (bp) mutation in ALDH7A1. Knock-out aldh7a1 embryos have spontaneous rapid increase in locomotion and a rapid circling swim behavior earliest 8-day post fertilization (dpf). Electroencephalogram revealed large amplitude spike discharges compared to wild type. Knock-out aldh7a1 embryos have elevated alpha-AASA, piperideine 6-carboxylate and pipecolic acid compared to wild type embryos at 3 dpf. Knock-out aldh7a1 embryos showed no aldh7a1 protein by western blot compared to wild type. Our knock-out aldh7a1 zebrafish is a well characterized model for large-scale drug screening using behavioral and biochemical features and accurately recapitulates the human PDE-ALDH7A1 disease.

Development of a one-step gene knock-out and knock-in method for metabolic engineering of Aureobasidium pullulans.

Science.gov (United States)

Guo, Jian; Wang, Yuanhua; Li, Baozhong; Huang, Siyao; Chen, Yefu; Guo, Xuewu; Xiao, Dongguang

2017-06-10

Aureobasidium pullulans is an increasingly attractive host for bio-production of pullulan, heavy oil, polymalic acid, and a large spectrum of extracellular enzymes. To date, genetic manipulation of A. pullulans mainly relies on time-consuming conventional restriction enzyme digestion and ligation methods. In this study, we present a one-step homologous recombination-based method for rapid genetic manipulation in A. pullulans. Overlaps measuring >40bp length and 10μg DNA segments for homologous recombination provided maximum benefits to transformation of A. pullulans. This optimized method was successfully applied to PKSIII gene (encodes polyketide synthase) knock-out and gltP gene (encodes glycolipid transfer protein) knock-in. After disruption of PKSIII gene, secretion of melanin decreased slightly. The melanin purified from disruptant showed lower reducing capacity compared with that of the parent strain, leading to a decrease in exopolysaccharide production. Knock-in of gltP gene resulted in at least 4.68-fold increase in heavy oil production depending on the carbon source used, indicating that gltP can regulate heavy oil synthesis in A. pullulans. Copyright © 2017 Elsevier B.V. All rights reserved.

Generation of Knock-in Mouse by Genome Editing.

Science.gov (United States)

Fujii, Wataru

2017-01-01

Knock-in mice are useful for evaluating endogenous gene expressions and functions in vivo. Instead of the conventional gene-targeting method using embryonic stem cells, an exogenous DNA sequence can be inserted into the target locus in the zygote using genome editing technology. In this chapter, I describe the generation of epitope-tagged mice using engineered endonuclease and single-stranded oligodeoxynucleotide through the mouse zygote as an example of how to generate a knock-in mouse by genome editing.

Evaluation of Knock Behavior for Natural Gas - Gasoline Blends in a Light Duty Spark Ignited Engine

Energy Technology Data Exchange (ETDEWEB)

Pamminger, Michael [Argonne National Lab. (ANL), Argonne, IL (United States); Sevik, James [Argonne National Lab. (ANL), Argonne, IL (United States); Scarcelli, Riccardo [Argonne National Lab. (ANL), Argonne, IL (United States); Wallner, Thomas [Argonne National Lab. (ANL), Argonne, IL (United States); Wooldridge, Steven [Ford Motor Co., Detroit, MI (United States); Boyer, Brad [Ford Motor Co., Detroit, MI (United States); Hall, Carrie M. [Illinois Inst. of Technology, Chicago, IL (United States)

2016-10-17

The compression ratio is a strong lever to increase the efficiency of an internal combustion engine. However, among others, it is limited by the knock resistance of the fuel used. Natural gas shows a higher knock resistance compared to gasoline, which makes it very attractive for use in internal combustion engines. The current paper describes the knock behavior of two gasoline fuels, and specific incylinder blend ratios with one of the gasoline fuels and natural gas. The engine used for these investigations is a single cylinder research engine for light duty application which is equipped with two separate fuel systems. Both fuels can be used simultaneously which allows for gasoline to be injected into the intake port and natural gas to be injected directly into the cylinder to overcome the power density loss usually connected with port fuel injection of natural gas. Adding natural gas at wide open throttle helps to reduce knock mitigating measures and increases the efficiency and power density compared to the other gasoline type fuels with lower knock resistance. The used methods, knock intensity and number of pressure waves, do not show significant differences in knock behavior for the natural gas - gasoline blends compared to the gasoline type fuels. A knock integral was used to describe the knock onset location of the fuels tested. Two different approaches were used to determine the experimental knock onset and were compared to the knock onset delivered by the knock integral (chemical knock onset). The gasoline type fuels show good agreement between chemical and experimental knock onset. However, the natural gas -gasoline blends show higher discrepancies comparing chemical and experimental knock onset.

Knock-on electrons in WA98 silicon drift detector

International Nuclear Information System (INIS)

Eliseev, S.

1997-01-01

Silicon Drift Detector is used to estimate production of knock-on electrons created by passage of 158 GeV /u fully stripped Pb ion through thick lead target. Analysed data were collected in 1995 during Pb+Pb run in WA98 heavy ion experiment at CERN SPS. Information from WA98 Cherenkov beam counter makes it possible to classify events according to number of additional Pb ions which have during detector's read-out time passed through the target without nuclear interaction. Events with one and none pile-up ion are used for statistical separation of knock-on electrons from all detected charged particles. Resulting inclusive spectra of knock-on electrons are compared with GRANT simulations and good agreement is found. (author)

Computational singular perturbation analysis of super-knock in SI engines

KAUST Repository

Jaasim, Mohammed; Tingas, Alexandros; Herná ndez Pé rez, Francisco E.; Im, Hong G.

2018-01-01

the deflagration front consumes the air/fuel mixture and two points located at 3 mm from the end-wall where super-knock and mild knock occur. The CSP analysis of the point at the center of the cylinder reveals weak two-stage ignition-like dynamics with a short

Knock knee and the gait of six-year-old children.

Science.gov (United States)

Pretkiewicz-Abacjew, E

2003-06-01

Knock knee (genu valgum) interferes with the locomotive and supporting function of the lower limb. In static conditions the load-bearing axis of the valgus limb is displaced laterally in relation to the middle of the joint, causing the knee joint, the ankle joint, and the foot as a whole to be weighted in the wrong way. The purpose of this work is to examine the influence of knock knee on gait kinematics. The gait of twenty-two 6-year-old children of both sexes in whom knock knee had been medically diagnosed was compared with the gait of 33 children of the same age whose knee joints conformed to the norm in formation and position. Gait was recorded separately for the sagittal and the frontal planes, using a video-computer system. The results of the examination indicated statistically significant differences in the gait of the two groups of children. These differences related mainly to the time features of gait and to data on the angles in the knee and ankle joints. Although the results obtained for other features of gait did not reveal statistical differences, these did indicate that the children with knock knee walked more slowly and with a lower cadence. The results indicate that knock knee in 6-year-old children has an adverse impact on the mechanics of the lower limb joints in gait and causes a deterioration in gait quality. Thus knock knee in children should not be treated merely as a superficial defect but should be subject to therapy and, more importantly, taken into account when introducing children to early sports training.

Partial LVAD restores ventricular outputs and normalizes LV but not RV stress distributions in the acutely failing heart in silico

OpenAIRE

Sack, Kevin L.; Baillargeon, Brian; Acevedo-Bolton, Gabriel; Genet, Martin; Rebelo, Nuno; Kuhl, Ellen; Klein, Liviu; Weiselthaler, Georg M.; Burkhoff, Daniel; Franz, Thomas; Guccione, Julius M.

2016-01-01

Purpose: Heart failure is a worldwide epidemic that is unlikely to change as the population ages and life expectancy increases. We sought to detail significant recent improvements to the Dassault Systèmes Living Heart Model (LHM) and use the LHM to compute left ventricular (LV) and right ventricular (RV) myofiber stress distributions under the following 4 conditions: (1) normal cardiac function; (2) acute left heart failure (ALHF); (3) ALHF treated using an LV assist device (LVAD) flow rate o...

Normal radiographic heart volume in the neonate. Pt. 3

International Nuclear Information System (INIS)

Dahlstroem, A.; Ringertz, H.G.; Sachsska Pediatric Hospital, Stockholm

1985-01-01

The diagnostic power of the heart volume and the cardiothoracic ratio in congenital heart disease in neonates has been compared. A consecutive series of 130 children with suspection of heart disease examined radiologically at between 48 h and 15 days of age were followed for 14+-10 months. Of these, 16 (12%) were diagnosed as having congenital heart disease. The number of false positive and negative diagnoses was less for heart volume than for cardiothoracic ratio using +2 SD as limit for pathology. Accuracy, sensitivity and specificity was 84, 75, and 85% respectively for heart volume and 73, 57, and 75% for cardiothoracic ratio. Cases that were false positive with both methods were significantly more often examined between 48 and 72 hours of age indicating that the explanation might be a somewhat late closure of the ductus arteriosus. (orig.)

RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency.

Science.gov (United States)

Song, Jun; Yang, Dongshan; Xu, Jie; Zhu, Tianqing; Chen, Y Eugene; Zhang, Jifeng

2016-01-28

Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells.

RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency

Science.gov (United States)

Song, Jun; Yang, Dongshan; Xu, Jie; Zhu, Tianqing; Chen, Y. Eugene; Zhang, Jifeng

2016-01-01

Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells. PMID:26817820

Motor Deficits and Cerebellar Atrophy in Elovl5 Knock Out Mice.

Science.gov (United States)

Hoxha, Eriola; Gabriele, Rebecca M C; Balbo, Ilaria; Ravera, Francesco; Masante, Linda; Zambelli, Vanessa; Albergo, Cristian; Mitro, Nico; Caruso, Donatella; Di Gregorio, Eleonora; Brusco, Alfredo; Borroni, Barbara; Tempia, Filippo

2017-01-01

Spino-Cerebellar-Ataxia type 38 (SCA38) is caused by missense mutations in the very long chain fatty acid elongase 5 gene, ELOVL5 . The main clinical findings in this disease are ataxia, hyposmia and cerebellar atrophy. Mice in which Elovl5 has been knocked out represent a model of the loss of function hypothesis of SCA38. In agreement with this hypothesis, Elovl5 knock out mice reproduced the main symptoms of patients, motor deficits at the beam balance test and hyposmia. The cerebellar cortex of Elovl5 knock out mice showed a reduction of thickness of the molecular layer, already detectable at 6 months of age, confirmed at 12 and 18 months. The total perimeter length of the Purkinje cell (PC) layer was also reduced in Elovl5 knock out mice. Since Elovl5 transcripts are expressed by PCs, whose dendrites are a major component of the molecular layer, we hypothesized that an alteration of their dendrites might be responsible for the reduced thickness of this layer. Reconstruction of the dendritic tree of biocytin-filled PCs, followed by Sholl analysis, showed that the distribution of distal dendrites was significantly reduced in Elovl5 knock out mice. Dendritic spine density was conserved. These results suggest that Elovl5 knock out mice recapitulate SCA38 symptoms and that their cerebellar atrophy is due, at least in part, to a reduced extension of PC dendritic arborization.

Staggering but not knocked out

Energy Technology Data Exchange (ETDEWEB)

Anon.

2012-11-01

Italy's PV market is staggering like a boxer almost knocked out. It has been hit hard by the country's deep economic recession. Conto Energia V has been yet another blow with cuts of up to 40 % in the solar feed-in tariffs. But the situation is not hopeless.

Performance and emission characteristics of turpentine-diesel dual fuel engine and knock suppression using water diluents

Energy Technology Data Exchange (ETDEWEB)

Karthikeyan, R. [Adhiparasakthi Engineering College, Tamil Nadu (India); Mahalakshmi, N.V. [College of Engineering Guindy, Tamil Nadu (India). Dept. of Mechanical Engineering

2007-08-15

In the present work, a normal diesel engine was modified to work in a dual fuel (DF) mode with turpentine and diesel as primary and pilot fuels, respectively. The resulting homogeneous mixture was compressed to a temperature below the self-ignition point. The pilot fuel was injected through the standard injection system and initiated the combustion in the primary-fuel air mixture. The primary fuel (turpentine) has supplied most of the heat energy. Usually, in all DF engines, low-cetane fuels are preferred as a primary fuel. Therefore, at higher loads these fuels start knocking and deteriorating in performances. Usually, DF operators suppress the knock by adding more pilot-fuel quantity. But in the present work, a minimum pilot-fuel quantity was maintained constant throughout the test and a required quantity of diluent (water) was added into the combustion at the time of knocking. The advantages of this method of knock suppression are restoration of performance at full load, maintenance of the same pilot quantity through the load range and reduction in the fuel consumption at full load. From the results, it was found that all performance and emission parameters of turpentine, except volumetric efficiency, are better than those of diesel fuel. The emissions like CO, UBHC are higher than those of the diesel baseline (DBL) and around 40-45% reduction of smoke was observed at 100% of full load. The major pollutant of diesel engine, NO{sub x}, was found to be equal to that of DBL. From the above experiment, it was proved that approximately 80% replacement of diesel with turpentine is quite possible. (author)

Acromegaly with Normal Insulin-Like Growth Factor-1 Levels and Congestive Heart Failure as the First Clinical Manifestation

Directory of Open Access Journals (Sweden)

Hyae Min Lee

2015-09-01

Full Text Available The leading cause of morbidity and mortality in patients with acromegaly is cardiovascular complications. Myocardial exposure to excessive growth hormone can cause ventricular hypertrophy, hypertension, arrhythmia, and diastolic dysfunction. However, congestive heart failure as a result of systolic dysfunction is observed only rarely in patients with acromegaly. Most cases of acromegaly exhibit high levels of serum insulin-like growth factor-1 (IGF-1. Acromegaly with normal IGF-1 levels is rare and difficult to diagnose. Here, we report a rare case of an acromegalic patient whose first clinical manifestation was severe congestive heart failure, despite normal IGF-1 levels. We diagnosed acromegaly using a glucose-loading growth hormone suppression test. Cardiac function and myocardial hypertrophy improved 6 months after transsphenoidal resection of a pituitary adenoma.

Anatomy of the normal fetal heart: The basis for understanding fetal echocardiography

Directory of Open Access Journals (Sweden)

Beatriz Picazo-Angelin

2018-01-01

Full Text Available The rapid changes that have taken place in recent years in relation to techniques used to image the fetal heart have emphasized the need to have a detailed knowledge ofnormal cardiac anatomy. Without such knowledge, it is difficult, if not impossible, to recognize the multiple facets of congenital cardiac disease. From the inception of fetal echocardiographic screening, the importance of basic knowledge of cardiac anatomy has been well recognized. The current machines used for imaging, however, now make it possible potentially to recognize features not appreciated at the start of the specialty. So as to match the advances made in imaging, we have now revisited our understanding of normal cardiac anatomy in the mid-gestational fetus. This was made possible by our dissection of 10 fetal hearts, followed by production of addition histological sections that mimic the standard ultrasound views. The fetuses ranged in gestational age from between 20 and 28 weeks. We then correlated the obtained anatomic images with the corresponding ultrasonic images used in the standard fetal screening scan. We also interrogated the anatomic sections so as to clarify ongoing controversies regarding detailed features of the normal cardiac anatomy. We have been able to show that the views now obtained using current technology reveal many details of anatomy not always appreciated at earlier times. Knowledge of these features should now permit diagnosis of most congenital cardiac malformations. The anatomic-echocardiographic correlations additionally provide a valuable resource for both the understanding and teaching of fetal echocardiography.

Impact of age and sex on normal left heart structure and function.

Science.gov (United States)

Hagström, Linn; Henein, Michael Y; Karp, Kjell; Waldenström, Anders; Lindqvist, Per

2017-11-01

Accurate age- and sex-related normal reference values of ventricular structure and function are important to determine the level of dysfunction in patients. The aim of this study therefore was to document normal age range sex-related measurements of LV structural and functional measurements to serve such purpose. We evaluated left ventricular structure and function in 293 healthy subjects between 20 and 90 years with equally distributed gender. Doppler echocardiography was used including measure of both systolic and diastolic functions. Due to systolic LV function, only long axis function correlated with age (r = 0·55, P<0·01) and the correlation was stronger in females. Concerning diastolic function, there was a strong age correlation in all parameters used (r = 0·40-0·74, P<0·001). Due to LV structural changes over age, females showed a larger reduction in end-diastolic volumes, but no or trivial difference in wall thickness after the age of 60 years. Age is associated with significant normal changes in left ventricular structure and function, which should be considered when deciding on normality. These changes are related to systemic arterial changes as well as body stature, thus reflecting overall body ageing process. Furthermore, normal cardiac ageing in females might partly explain the higher prevalence of heart failure with preserved ejection in females. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Knock down of the myostatin gene by RNA interference increased body weight in chicken.

Science.gov (United States)

Bhattacharya, T K; Shukla, R; Chatterjee, R N; Dushyanth, K

2017-01-10

Myostatin is a negative regulator of muscular growth in poultry and other animals. Of several approaches, knocking down the negative regulator is an important aspect to augment muscular growth in chicken. Knock down of myostatin gene has been performed by shRNA acting against the expression of gene in animals. Two methods of knock down of gene in chicken such as embryo manipulation and sperm mediated method have been performed. The hatching percentage in embryo manipulation and sperm mediated method of knock down was 58.0 and 41.5%, respectively. The shRNA in knock down chicken enhanced body weight at 6 weeks by 26.9%. The dressing percentage and serum biochemical parameters such as SGPT and alkaline phosphatase differed significantly (Pknock down and control birds. It is concluded that knocking down the myostatin gene successfully augmented growth in chicken. Copyright © 2016 Elsevier B.V. All rights reserved.

System and method for controlling engine knock using electro-hydraulic valve actuation

Science.gov (United States)

Brennan, Daniel G

2013-12-10

A control system for an engine includes a knock control module and a valve control module. The knock control module adjusts a period that one or more of an intake valve and an exhaust valve of a cylinder are open based on engine knock corresponding to the cylinder. The valve control module, based on the adjusted period, controls the one or more of the intake valve and the exhaust valve using one or more hydraulic actuators.

Development and evaluation of an efficient heterologous gene knock-in reporter system in Lactococcus lactis.

Science.gov (United States)

Lu, Yifei; Yan, Hongxiang; Deng, Jiezhong; Huang, Zhigang; Jin, Xurui; Yu, Yanlan; Hu, Qiwen; Hu, Fuquan; Wang, Jing

2017-09-18

Lactococcus lactis is a food grade probiotics and widely used to express heterologous proteins. Generally, target genes are knocked into the L. lactis genome through double-crossover recombination to express heterologous proteins stably. However, creating marker-less heterologous genes knocked-in clones is laborious. In this study, an efficient heterologous gene knock-in reporter system was developed in L. lactis NZ9000. Our knock-in reporter system consists of a temperature-sensitive plasmid pJW and a recombinant L. lactis strain named NZB. The pJW contains homologous arms, and was constructed to knock-in heterologous genes at a fixed locus of NZ9000 genome. lacZ (β-galactosidase) gene was knocked into the chromosome of NZ9000 as a counter-selective marker through the plasmid pJW to generate NZB. The engineered NZB strain formed blue colonies on X-Gal plate. The desired double-crossover mutants formed white colonies distinctive from the predominantly blue colonies (parental and plasmid-integrated clones) when the embedded lacZ was replaced with the target heterologous genes carried by pJW in NZB. By using the system, the heterologous gene knocked-in clones are screened by colony phenotype change rather than by checking colonies individually. Our new knock-in reporter system provides an efficient method to create heterologous genes knocked-in clones.

Experimental investigation on the knocking combustion characteristics of n-butanol gasoline blends in a DISI engine

International Nuclear Information System (INIS)

Wei, Haiqiao; Feng, Dengquan; Pan, Mingzhang; Pan, JiaYing; Rao, XiaoKang; Gao, Dongzhi

2016-01-01

Highlights: • N-butanol shows better knock resistance characterized by improved KLST. • Bu20 blend fuel slightly degrades the knock resistance compared with gasoline. • Knock oscillation frequency depends on combustion chamber resonance modes. • Probability distribution is applied to evaluate variation of knock intensity. - Abstract: n-Butanol is a very competitive alternative biofuel for spark ignition (SI) engines given its many advantages. Current researches are mainly concentrated on the overall combustion and emissions performance concerning the feasibility of n-butanol gasoline blends in SI engines. In this work, focus was given on the knocking combustion characteristics of operation with pure n-butanol as well as a blend fuel with 20% volume content of n-butanol (Bu20), which was investigated experimentally in a direct-injection spark ignition (DISI) single cylinder engine. Operation condition is fixed at a constant engine speed of 1500 r/min, using three throttle openings with stoichiometric air–fuel ratio. Spark timing was swept to achieve different knocking levels. The results of n-butanol and Bu20 were benchmarked against those obtained by the research octane number (RON) 92 commercial gasoline. Compared with the baseline fuel gasoline, neat n-butanol shows better anti-knock ability with more advanced knock limited spark timing, whereas slightly deteriorative knock resistance can be found for Bu20. It is hypothesized Bu20 has higher end gas temperature due to its higher brake mean effective pressure (BMEP) and faster burning rate compared with gasoline, which indicates the knock tendency depends not only on the fuel octane number, but also on the factors that affect the end gas thermodynamic state. The heavier knock propensity of Bu20 is furthermore confirmed by its more advanced knock onset and higher peak oscillation pressure. Results of fast fourier transform (FFT) indicate the knocking oscillation frequencies are mainly determined by the

Dimensional analysis of heart rate variability in heart transplant recipients

Energy Technology Data Exchange (ETDEWEB)

Zbilut, J.P.; Mayer-Kress, G.; Geist, K.

1987-01-01

We discuss periodicities in the heart rate in normal and transplanted hearts. We then consider the possibility of dimensional analysis of these periodicities in transplanted hearts and problems associated with the record.

Development of versatile non-homologous end joining-based knock-in module for genome editing.

Science.gov (United States)

Sawatsubashi, Shun; Joko, Yudai; Fukumoto, Seiji; Matsumoto, Toshio; Sugano, Shigeo S

2018-01-12

CRISPR/Cas9-based genome editing has dramatically accelerated genome engineering. An important aspect of genome engineering is efficient knock-in technology. For improved knock-in efficiency, the non-homologous end joining (NHEJ) repair pathway has been used over the homology-dependent repair pathway, but there remains a need to reduce the complexity of the preparation of donor vectors. We developed the versatile NHEJ-based knock-in module for genome editing (VIKING). Using the consensus sequence of the time-honored pUC vector to cut donor vectors, any vector with a pUC backbone could be used as the donor vector without customization. Conditions required to minimize random integration rates of the donor vector were also investigated. We attempted to isolate null lines of the VDR gene in human HaCaT keratinocytes using knock-in/knock-out with a selection marker cassette, and found 75% of clones isolated were successfully knocked-in. Although HaCaT cells have hypotetraploid genome composition, the results suggest multiple clones have VDR null phenotypes. VIKING modules enabled highly efficient knock-in of any vectors harboring pUC vectors. Users now can insert various existing vectors into an arbitrary locus in the genome. VIKING will contribute to low-cost genome engineering.

The Science of Hard Knocks

Science.gov (United States)

Vance, Erik

2007-01-01

Head injuries in sports are nothing new, but in recent years, college athletes have reported a steady rise in concussions. Football players still get the most knocks to the head. Women have managed to keep up with, and often surpass, men in sports-related concussions in the last few years. In basketball, women reported 24 percent more concussions…

Factors related to outcome in heart failure with a preserved (or normal) left ventricular ejection fraction.

Science.gov (United States)

Sanderson, John E

2016-07-01

Heart failure with a preserved ejection faction (HFpEF) is a growing and expensive cause of heart failure (HF) affecting particularly the elderly. It differs in substantial ways in addition to the normal left ventricular ejection fraction, from the more easily recognized form of heart failure with a reduced ejection fraction (HFrEF or 'systolic heart failure') and unlike HFrEF there have been little advances in treatment. In part, this relates to the complexity of the pathophysiology and identifying the correct targets. In HFpEF, there appears to be widespread stiffening of the vasculature and the myocardium affecting ventricular function (both systolic and diastolic), impeding ventricular suction, and thus early diastolic filling leading to breathlessness on exertion and later atrial failure and fibrillation. Left ventricular ejection fraction tends to gradually decline and some evolve into HFrEF. Most patients also have a mixture of several co-morbidities including hypertension, diabetes, obesity, poor renal function, lack of fitness, and often poor social conditions. Therefore, many factors may influence outcome in an individual patient. In this review, the epidemiology, possible causation, pathophysiology, the influence of co-morbidities and some of the many potential predictors of outcome will be considered.

Dynamic knock detection and quantification in a spark ignition engine by means of a pressure based method

International Nuclear Information System (INIS)

Galloni, Enzo

2012-01-01

Highlights: ► Experimental data have been analyzed by a pressure based method. ► Knock intensity level depends on a threshold varying with the engine operating point. ► A dynamic method is proposed to overcome the definition of a predetermined threshold. ► The knock intensity of each operating point is quantified by a dimensionless index. ► The knock limited spark advance can be detected by means of this index. - Abstract: In spark ignition engines, knock onset limits the maximum spark advance. An inaccurate identification of this limit penalises the fuel conversion efficiency. Thus it is very important to define a knock detection method able to assess the knock intensity of an engine operating point. Usually, in engine development, knock event is evaluated by analysing the in-cylinder pressure trace. Data are filtered and processed in order to obtain some indices correlated to the knock intensity, then the calculated value is compared to a predetermined threshold. The calibration of this threshold is complex and difficult; statistical approach should be used, but often empirical values are considered. In this paper a method that dynamically calculates the knock threshold necessary to determine the knock event is proposed. The purpose is to resolve cycle by cycle the knock intensity related to an individual engine cycle without setting a predetermined threshold. The method has been applied to an extensive set of experimental data relative to a gasoline spark-ignition engine. Results are correlated to those obtained considering a traditional method, where a statistical approach has been used to detect knock.

Source characteristics of the underwater knocking displays of a male Pacific walrus (Odobenus rosmarus divergens)

DEFF Research Database (Denmark)

Hughes, William R.; Reichmuth, Colleen; Mulsow, Jason L.

2011-01-01

"knocks"’ punctuated by occasional metallic "bells." The source characteristics of the knocking sounds that were regularly emitted by a male walrus raised in captivity were examined. Knocks were produced as single 20 ms pulses, or as doublets and triplets, and were typically repeated at rates of 0.8/s...... to 1.2/s. These were loud sounds with greater bandwidth than previously reported: mean source levels were 186 dB pk-pk re 1 Pa at 1 m (range 164-196) with maximum frequency >24 kHz. Production of each knock was associated with visible impulsive movement of the forehead. During rut, this walrus had...... difficulty inhibiting sound production and would often continue to emit knocks in air during haul-out and even while eating, suggesting an endogenous component to this behavior. A strong correlation between his seasonal testosterone levels and the persistence of knocking displays was confirmed. Captive...

Establishment of expanded and streamlined pipeline of PITCh knock-in - a web-based design tool for MMEJ-mediated gene knock-in, PITCh designer, and the variations of PITCh, PITCh-TG and PITCh-KIKO.

Science.gov (United States)

Nakamae, Kazuki; Nishimura, Yuki; Takenaga, Mitsumasa; Nakade, Shota; Sakamoto, Naoaki; Ide, Hiroshi; Sakuma, Tetsushi; Yamamoto, Takashi

2017-05-04

The emerging genome editing technology has enabled the creation of gene knock-in cells easily, efficiently, and rapidly, which has dramatically accelerated research in the field of mammalian functional genomics, including in humans. We recently developed a microhomology-mediated end-joining-based gene knock-in method, termed the PITCh system, and presented various examples of its application. Since the PITCh system only requires very short microhomologies (up to 40 bp) and single-guide RNA target sites on the donor vector, the targeting construct can be rapidly prepared compared with the conventional targeting vector for homologous recombination-based knock-in. Here, we established a streamlined pipeline to design and perform PITCh knock-in to further expand the availability of this method by creating web-based design software, PITCh designer ( http://www.mls.sci.hiroshima-u.ac.jp/smg/PITChdesigner/index.html ), as well as presenting an experimental example of versatile gene cassette knock-in. PITCh designer can automatically design not only the appropriate microhomologies but also the primers to construct locus-specific donor vectors for PITCh knock-in. By using our newly established pipeline, a reporter cell line for monitoring endogenous gene expression, and transgenesis (TG) or knock-in/knockout (KIKO) cell line can be produced systematically. Using these new variations of PITCh, an exogenous promoter-driven gene cassette expressing fluorescent protein gene and drug resistance gene can be integrated into a safe harbor or a specific gene locus to create transgenic reporter cells (PITCh-TG) or knockout cells with reporter knock-in (PITCh-KIKO), respectively.

Global Bi-ventricular endocardial distribution of activation rate during long duration ventricular fibrillation in normal and heart failure canines.

Science.gov (United States)

Luo, Qingzhi; Jin, Qi; Zhang, Ning; Han, Yanxin; Wang, Yilong; Huang, Shangwei; Lin, Changjian; Ling, Tianyou; Chen, Kang; Pan, Wenqi; Wu, Liqun

2017-04-13

The objective of this study was to detect differences in the distribution of the left and right ventricle (LV & RV) activation rate (AR) during short-duration ventricular fibrillation (SDVF, 1 min) in normal and heart failure (HF) canine hearts. Ventricular fibrillation (VF) was electrically induced in six healthy dogs (control group) and six dogs with right ventricular pacing-induced congestive HF (HF group). Two 64-electrode basket catheters deployed in the LV and RV were used for global endocardium electrical mapping. The AR of VF was estimated by fast Fourier transform analysis from each electrode. In the control group, the LV was activated faster than the RV in the first 20 s, after which there was no detectable difference in the AR between them. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the posterior LV was activated fastest, while the anterior was slowest. In the HF group, a detectable AR gradient existed between the two ventricles within 3 min of VF, with the LV activating more quickly than the RV. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the septum of the LV was activated fastest, while the anterior was activated slowest. A global bi-ventricular endocardial AR gradient existed within the first 20 s of VF but disappeared in the LDVF in healthy hearts. However, the AR gradient was always observed in both SDVF and LDVF in HF hearts. The findings of this study suggest that LDVF in HF hearts can be maintained differently from normal hearts, which accordingly should lead to the development of different management strategies for LDVF resuscitation.

Is "treat your child normally" helpful advice for parents of survivors of treatment of hypoplastic left heart syndrome?

Science.gov (United States)

Rempel, Gwen R; Harrison, Margaret J; Williamson, Deanna L

2009-04-01

Developing technology affords children with complex congenitally malformed hearts a chance for survival. Parents gratefully pursue life-saving options on behalf of their children, despite the risks to the life of their child, and uncertainty about outcomes. Little is known about how mothers and fathers experience parenting a child whose new state as a survivor may include less than optimal developmental sequels. Our study involved multiple interactive interviews with 9 mothers and 7 fathers of infants and preschool children with hypoplastic left heart syndrome who had survived the Norwood surgical approach. Qualitative methodology included grounded theory methods of simultaneous collection and analysis of data, and we used open and selective coding of transcribed interviews. Parents used normalization in the context of uncertainty regarding the ongoing survival of their child. Parents described their underweight children as being on their own growth curve, and viewed their developmental progress, however delayed, as reason for celebration, as they had been prepared for their child to die. There is growing evidence that children with congenitally malformed hearts who require surgical intervention during the first year of life may experience developmental delay. The use of normalization by their parents may be effective in decreasing their worry regarding the uncertain future faced by their child, but may negatively affect the developmental progress of the child if they do not seek resources to assist development. Advice from paediatric specialists for parents to view their children as normal needs to be balanced with assistance for parents to access services to support optimal growth and development of their child.

Metaiodobenzylguanidine and heart rate variability in heart failure

International Nuclear Information System (INIS)

Kurata, Chinori; Shouda, Sakae; Mikami, Tadashi; Uehara, Akihiko; Ishikawa, Keiko; Tawarahara, Kei; Nakano, Tomoyasu; Matoh, Fumitaka; Takeuchi, Kazuhiko

1998-01-01

It is assumed that the low-frequency power (LF) of heart rate variability (HRV) increases with progress of congestive heart failure (CHF), therefore positively correlating with cardiac 123 I-metaiodobenzylguanidine (MIBG) washout. It is demonstrated here that HRV, including normalized LF, correlated inversely with MIBG washout and positively with the ratio of heart-to-mediastinum MIBG activity in controls and CHF patients, whereas these correlations were not observed within CHF patients. Thus MIBG washout may increase and HRV including normalized LF may decrease with CHF, although the HRV and MIBG measures may not similarly change in proportion to the severity of the cardiac autonomic dysfunction in CHF. (author)

Metaiodobenzylguanidine and heart rate variability in heart failure

Energy Technology Data Exchange (ETDEWEB)

Kurata, Chinori; Shouda, Sakae; Mikami, Tadashi; Uehara, Akihiko; Ishikawa, Keiko [Hamamatsu Univ., Shizuoka (Japan). School of Medicine; Tawarahara, Kei; Nakano, Tomoyasu; Matoh, Fumitaka; Takeuchi, Kazuhiko

1998-10-01

It is assumed that the low-frequency power (LF) of heart rate variability (HRV) increases with progress of congestive heart failure (CHF), therefore positively correlating with cardiac {sup 123}I-metaiodobenzylguanidine (MIBG) washout. It is demonstrated here that HRV, including normalized LF, correlated inversely with MIBG washout and positively with the ratio of heart-to-mediastinum MIBG activity in controls and CHF patients, whereas these correlations were not observed within CHF patients. Thus MIBG washout may increase and HRV including normalized LF may decrease with CHF, although the HRV and MIBG measures may not similarly change in proportion to the severity of the cardiac autonomic dysfunction in CHF. (author)

Brain catecholamine depletion and motor impairment in a Th knock-in mouse with type B tyrosine hydroxylase deficiency.

Science.gov (United States)

Korner, Germaine; Noain, Daniela; Ying, Ming; Hole, Magnus; Flydal, Marte I; Scherer, Tanja; Allegri, Gabriella; Rassi, Anahita; Fingerhut, Ralph; Becu-Villalobos, Damasia; Pillai, Samyuktha; Wueest, Stephan; Konrad, Daniel; Lauber-Biason, Anna; Baumann, Christian R; Bindoff, Laurence A; Martinez, Aurora; Thöny, Beat

2015-10-01

Tyrosine hydroxylase catalyses the hydroxylation of L-tyrosine to l-DOPA, the rate-limiting step in the synthesis of catecholamines. Mutations in the TH gene encoding tyrosine hydroxylase are associated with the autosomal recessive disorder tyrosine hydroxylase deficiency, which manifests phenotypes varying from infantile parkinsonism and DOPA-responsive dystonia, also termed type A, to complex encephalopathy with perinatal onset, termed type B. We generated homozygous Th knock-in mice with the mutation Th-p.R203H, equivalent to the most recurrent human mutation associated with type B tyrosine hydroxylase deficiency (TH-p.R233H), often unresponsive to l-DOPA treatment. The Th knock-in mice showed normal survival and food intake, but hypotension, hypokinesia, reduced motor coordination, wide-based gate and catalepsy. This phenotype was associated with a gradual loss of central catecholamines and the serious manifestations of motor impairment presented diurnal fluctuation but did not improve with standard l-DOPA treatment. The mutant tyrosine hydroxylase enzyme was unstable and exhibited deficient stabilization by catecholamines, leading to decline of brain tyrosine hydroxylase-immunoreactivity in the Th knock-in mice. In fact the substantia nigra presented an almost normal level of mutant tyrosine hydroxylase protein but distinct absence of the enzyme was observed in the striatum, indicating a mutation-associated mislocalization of tyrosine hydroxylase in the nigrostriatal pathway. This hypomorphic mouse model thus provides understanding on pathomechanisms in type B tyrosine hydroxylase deficiency and a platform for the evaluation of novel therapeutics for movement disorders with loss of dopaminergic input to the striatum. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Correcting human heart 31P NMR spectra for partial saturation. Evidence that saturation factors for PCr/ATP are homogeneous in normal and disease states

Science.gov (United States)

Bottomley, Paul A.; Hardy, Christopher J.; Weiss, Robert G.

Heart PCr/ATP ratios measured from spatially localized 31P NMR spectra can be corrected for partial saturation effects using saturation factors derived from unlocalized chest surface-coil spectra acquired at the heart rate and approximate Ernst angle for phosphor creatine (PCr) and again under fully relaxed conditions during each 31P exam. To validate this approach in studies of normal and disease states where the possibility of heterogeneity in metabolite T1 values between both chest muscle and heart and normal and disease states exists, the properties of saturation factors for metabolite ratios were investigated theoretically under conditions applicable in typical cardiac spectroscopy exams and empirically using data from 82 cardiac 31P exams in six study groups comprising normal controls ( n = 19) and patients with dilated ( n = 20) and hypertrophic ( n = 5) cardiomyopathy, coronary artery disease ( n = 16), heart transplants ( n = 19), and valvular heart disease ( n = 3). When TR ≪ T1,(PCr), with T1(PCr) ⩾ T1(ATP), the saturation factor for PCr/ATP lies in the range 1.5 ± 0.5, regardless of the T1 values. The precise value depends on the ratio of metabolite T1 values rather than their absolute values and is insensitive to modest changes in TR. Published data suggest that the metabolite T1 ratio is the same in heart and muscle. Our empirical data reveal that the saturation factors do not vary significantly with disease state, nor with the relative fractions of muscle and heart contributing to the chest surface-coil spectra. Also, the corrected myocardial PCr/ATP ratios in each normal or disease state bear no correlation with the corresponding saturation factors nor the fraction of muscle in the unlocalized chest spectra. However, application of the saturation correction (mean value, 1.36 ± 0.03 SE) significantly reduced scatter in myocardial PCr/ATP data by 14 ± 11% (SD) ( p ⩽ 0.05). The findings suggest that the relative T1 values of PCr and ATP are

Sensitivity of dual fuel engine combustion and knocking limits to gaseous fuel composition

Energy Technology Data Exchange (ETDEWEB)

Selim, M.Y.E. [United Arab Emirates University, Al-Ain (United Arab Emirates). Dept. of Mechanical Engineering

2004-02-01

Combustion noise, knock and ignition limits data are measured and presented for a dual fuel engine running on dual fuels of Diesel and three gaseous fuels separately. The gaseous fuels used are liquefied petroleum gas, pure methane and compressed natural gas mixture. The maximum pressure rise rate during combustion is presented as a measure of combustion noise, and the knocking and ignition limits are presented as torque output at the onset of knocking and ignition failure. Experimental investigation on the dual fuel engine revealed the noise generated from combustion, knocking and ignition limits for all gases at different design and operating conditions. A Ricardo E6 Diesel version engine is converted to run on dual fuel of Diesel and the tested gaseous fuel and is used throughout the work. The engine is fully computerized, and the cylinder pressure data, crank angle data and engine operating variables are stored in a PC for off line analysis. The effects of engine speeds, loads, pilot injection angle, pilot fuel quantity and compression ratio on combustion noise, knocking torque, thermal efficiency and maximum pressure are examined for the dual engine running on the three gaseous fuels separately. The combustion noise, knocking and ignition limits are found to relate to the type of gaseous fuels and to the engine design and operating parameters. (author)

Sensitivity of dual fuel engine combustion and knocking limits to gaseous fuel composition

International Nuclear Information System (INIS)

Selim, Mohamed Y.E.

2004-01-01

Combustion noise, knock and ignition limits data are measured and presented for a dual fuel engine running on dual fuels of Diesel and three gaseous fuels separately. The gaseous fuels used are liquefied petroleum gas, pure methane and compressed natural gas mixture. The maximum pressure rise rate during combustion is presented as a measure of combustion noise, and the knocking and ignition limits are presented as torque output at the onset of knocking and ignition failure. Experimental investigation on the dual fuel engine revealed the noise generated from combustion, knocking and ignition limits for all gases at different design and operating conditions. A Ricardo E6 Diesel version engine is converted to run on dual fuel of Diesel and the tested gaseous fuel and is used throughout the work. The engine is fully computerized, and the cylinder pressure data, crank angle data and engine operating variables are stored in a PC for off line analysis. The effects of engine speeds, loads, pilot injection angle, pilot fuel quantity and compression ratio on combustion noise, knocking torque, thermal efficiency and maximum pressure are examined for the dual engine running on the three gaseous fuels separately. The combustion noise, knocking and ignition limits are found to relate to the type of gaseous fuels and to the engine design and operating parameters

Profile of Cardiovascular Risk Factors in Patients with Coronary Heart Disease, Normal and Impaired Carbohydrate Metabolism

Directory of Open Access Journals (Sweden)

І.V. Cherniavska

2015-11-01

Full Text Available The aim of research was to conduct the comparative analysis of the profile of cardiovascular risk factors in patients with coronary heart disease (CHD and normal either impaired carbohydrate metabolism. Materials and methods. One hundred and forty two patients were observed. In order to estimate the rate of different forms of CHD depending on the state of carbohydrate metabolism such groups were formed: the first group consisted of 83 patients with type 2 diabetes mellitus (DM, the second group involved 34 patients with impaired glucose tolerance (IGT, the third group consisted of 25 patients with normal carbohydrate metabolism. The ischemic changes of myocardium were detected by ambulatory ECG monitoring with the obligatory achievement of submaximal heart rate during the research. Results. Silent myocardial ischemia was educed in 19 (22.9 % patients with type 2 DM, in 3 (8.8 % persons with IGT and in 2 (8.0 % patients with normal carbohydrate metabolism. Smoking, burdened heredity, violation in the haemostatic system more often occurred in the group of patients with type 2 DM and silent myocardial ischemia in comparison with the patients with type 2 DM without CHD. The profile of general population cardiovascular risk factors in patients with CHD and type 2 DM belongs to the most unfavorable. At the same time for patients with early violations of carbohydrate metabolism and normal carbohydrate metabolism such profile statistically does not differentiate meaningfully. Conclusions. Patients with type 2 DM and silent myocardial ischemia as compared to patients with type 2 DM without CHD have more expressed violations of indexes of general population cardiovascular risk factors for certain.

Establishment of expanded and streamlined pipeline of PITCh knock-in – a web-based design tool for MMEJ-mediated gene knock-in, PITCh designer, and the variations of PITCh, PITCh-TG and PITCh-KIKO

Science.gov (United States)

Nakamae, Kazuki; Nishimura, Yuki; Takenaga, Mitsumasa; Sakamoto, Naoaki; Ide, Hiroshi; Sakuma, Tetsushi; Yamamoto, Takashi

2017-01-01

ABSTRACT The emerging genome editing technology has enabled the creation of gene knock-in cells easily, efficiently, and rapidly, which has dramatically accelerated research in the field of mammalian functional genomics, including in humans. We recently developed a microhomology-mediated end-joining-based gene knock-in method, termed the PITCh system, and presented various examples of its application. Since the PITCh system only requires very short microhomologies (up to 40 bp) and single-guide RNA target sites on the donor vector, the targeting construct can be rapidly prepared compared with the conventional targeting vector for homologous recombination-based knock-in. Here, we established a streamlined pipeline to design and perform PITCh knock-in to further expand the availability of this method by creating web-based design software, PITCh designer (http://www.mls.sci.hiroshima-u.ac.jp/smg/PITChdesigner/index.html), as well as presenting an experimental example of versatile gene cassette knock-in. PITCh designer can automatically design not only the appropriate microhomologies but also the primers to construct locus-specific donor vectors for PITCh knock-in. By using our newly established pipeline, a reporter cell line for monitoring endogenous gene expression, and transgenesis (TG) or knock-in/knockout (KIKO) cell line can be produced systematically. Using these new variations of PITCh, an exogenous promoter-driven gene cassette expressing fluorescent protein gene and drug resistance gene can be integrated into a safe harbor or a specific gene locus to create transgenic reporter cells (PITCh-TG) or knockout cells with reporter knock-in (PITCh-KIKO), respectively. PMID:28453368

DJ-1 KNOCK-DOWN IMPAIRS ASTROCYTE MITOCHONDRIAL FUNCTION

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LARSEN, N. J.; AMBROSI, G.; MULLETT, S. J.; BERMAN, S. B.; HINKLE, D. A.

2012-01-01

Mitochondrial dysfunction has long been implicated in the pathogenesis of Parkinson’s disease (PD). PD brain tissues show evidence for mitochondrial respiratory chain Complex I deficiency. Pharmacological inhibitors of Complex I, such as rotenone, cause experimental parkinsonism. The cytoprotective protein DJ-1, whose deletion is sufficient to cause genetic PD, is also known to have mitochondria-stabilizing properties. We have previously shown that DJ-1 is over-expressed in PD astrocytes, and that DJ-1 deficiency impairs the capacity of astrocytes to protect co-cultured neurons against rotenone. Since DJ-1 modulated, astrocyte-mediated neuroprotection against rotenone may depend upon proper astrocytic mitochondrial functioning, we hypothesized that DJ-1 deficiency would impair astrocyte mitochondrial motility, fission/fusion dynamics, membrane potential maintenance, and respiration, both at baseline and as an enhancement of rotenone-induced mitochondrial dysfunction. In astrocyte-enriched cultures, we observed that DJ-1 knock-down reduced mitochondrial motility primarily in the cellular processes of both untreated and rotenone treated cells. In these same cultures, DJ-1 knock-down did not appreciably affect mitochondrial fission, fusion, or respiration, but did enhance rotenone-induced reductions in the mitochondrial membrane potential. In neuron–astrocyte co-cultures, astrocytic DJ-1 knock-down reduced astrocyte process mitochondrial motility in untreated cells, but this effect was not maintained in the presence of rotenone. In the same co-cultures, astrocytic DJ-1 knock-down significantly reduced mitochondrial fusion in the astrocyte cell bodies, but not the processes, under the same conditions of rotenone treatment in which DJ-1 deficiency is known to impair astrocyte-mediated neuroprotection. Our studies therefore demonstrated the following new findings: (i) DJ-1 deficiency can impair astrocyte mitochondrial physiology at multiple levels, (ii) astrocyte

Parallel knock-out schemes in networks

NARCIS (Netherlands)

Broersma, H.J.; Fomin, F.V.; Woeginger, G.J.

2004-01-01

We consider parallel knock-out schemes, a procedure on graphs introduced by Lampert and Slater in 1997 in which each vertex eliminates exactly one of its neighbors in each round. We are considering cases in which after a finite number of rounds, where the minimimum number is called the parallel

Improved motor performance in Dyt1 ΔGAG heterozygous knock-in mice by cerebellar Purkinje-cell specific Dyt1 conditional knocking-out.

Science.gov (United States)

Yokoi, Fumiaki; Dang, Mai Tu; Li, Yuqing

2012-05-01

Early-onset generalized torsion dystonia (dystonia 1) is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most patients have a 3-base pair deletion (ΔGAG) in one allele of DYT1, corresponding to a loss of a glutamic acid residue (ΔE) in the C-terminal region of the protein. Functional alterations in basal ganglia circuits and the cerebellum have been reported in dystonia. Pharmacological manipulations or mutations in genes that result in functional alterations of the cerebellum have been reported to have dystonic symptoms and have been used as phenotypic rodent models. Additionally, structural lesions in the abnormal cerebellar circuits, such as cerebellectomy, have therapeutic effects in these models. A previous study has shown that the Dyt1 ΔGAG heterozygous knock-in (KI) mice exhibit motor deficits in the beam-walking test. Both Dyt1 ΔGAG heterozygous knock-in (KI) and Dyt1 Purkinje cell-specific knockout (Dyt1 pKO) mice exhibit dendritic alterations of cerebellar Purkinje cells. Here, Dyt1 pKO mice exhibited significantly less slip numbers in the beam-walking test, suggesting better motor performance than control littermates, and normal gait. Furthermore, Dyt1 ΔGAG KI/Dyt1 pKO double mutant mice exhibited significantly lower numbers of slips than Dyt1 ΔGAG heterozygous KI mice, suggesting Purkinje-cell specific knockout of Dyt1 wild-type (WT) allele in Dyt1 ΔGAG heterozygous KI mice rescued the motor deficits. The results suggest that molecular lesions of torsinA in Purkinje cells by gene therapy or intervening in the signaling pathway downstream of the cerebellar Purkinje cells may rescue motor symptoms in dystonia 1. Copyright © 2012 Elsevier B.V. All rights reserved.

The kick-in system: a novel rapid knock-in strategy.

Science.gov (United States)

Tomonoh, Yuko; Deshimaru, Masanobu; Araki, Kimi; Miyazaki, Yasuhiro; Arasaki, Tomoko; Tanaka, Yasuyoshi; Kitamura, Haruna; Mori, Fumiaki; Wakabayashi, Koichi; Yamashita, Sayaka; Saito, Ryo; Itoh, Masayuki; Uchida, Taku; Yamada, Junko; Migita, Keisuke; Ueno, Shinya; Kitaura, Hiroki; Kakita, Akiyoshi; Lossin, Christoph; Takano, Yukio; Hirose, Shinichi

2014-01-01

Knock-in mouse models have contributed tremendously to our understanding of human disorders. However, generation of knock-in animals requires a significant investment of time and effort. We addressed this problem by developing a novel knock-in system that circumvents several traditional challenges by establishing stem cells with acceptor elements enveloping a particular genomic target. Once established, these acceptor embryonic stem (ES) cells are efficient at directionally incorporating mutated target DNA using modified Cre/lox technology. This is advantageous, because knock-ins are not restricted to one a priori selected variation. Rather, it is possible to generate several mutant animal lines harboring desired alterations in the targeted area. Acceptor ES cell generation is the rate-limiting step, lasting approximately 2 months. Subsequent manipulations toward animal production require an additional 8 weeks, but this delimits the full period from conception of the genetic alteration to its animal incorporation. We call this system a "kick-in" to emphasize its unique characteristics of speed and convenience. To demonstrate the functionality of the kick-in methodology, we generated two mouse lines with separate mutant versions of the voltage-dependent potassium channel Kv7.2 (Kcnq2): p.Tyr284Cys (Y284C) and p.Ala306Thr (A306T); both variations have been associated with benign familial neonatal epilepsy. Adult mice homozygous for Y284C, heretofore unexamined in animals, presented with spontaneous seizures, whereas A306T homozygotes died early. Heterozygous mice of both lines showed increased sensitivity to pentylenetetrazole, possibly due to a reduction in M-current in CA1 hippocampal pyramidal neurons. Our observations for the A306T animals match those obtained with traditional knock-in technology, demonstrating that the kick-in system can readily generate mice bearing various mutations, making it a suitable feeder technology toward streamlined phenotyping.

Computer simulation of energy dissipation from near threshold knock-ons in Fe3Al

International Nuclear Information System (INIS)

Schade, G.; Leighly, H.P. Jr.; Edwards, D.R.

1976-01-01

A computer program has been developed and used to model a series of knock-ons near the damage energy threshold in a micro-crystallite of the ordered alloy Fe 3 Al. The primary paths of energy removal from the knock-on site were found to be along the [100] and [111] directions by means of focusing type collision chains. The relative importance of either direction as an energy removal path varied with the initial knock-on direction and also changed with time during the course of the knock-on event. The time rate of energy removal was found to be greatest in the [111] direction due to the shorter interatomic distances between atoms along this direction

Evolution and development of ventricular septation in the amniote heart.

Directory of Open Access Journals (Sweden)

Robert E Poelmann

Full Text Available During cardiogenesis the epicardium, covering the surface of the myocardial tube, has been ascribed several functions essential for normal heart development of vertebrates from lampreys to mammals. We investigated a novel function of the epicardium in ventricular development in species with partial and complete septation. These species include reptiles, birds and mammals. Adult turtles, lizards and snakes have a complex ventricle with three cava, partially separated by the horizontal and vertical septa. The crocodilians, birds and mammals with origins some 100 million years apart, however, have a left and right ventricle that are completely separated, being a clear example of convergent evolution. In specific embryonic stages these species show similarities in development, prompting us to investigate the mechanisms underlying epicardial involvement. The primitive ventricle of early embryos becomes septated by folding and fusion of the anterior ventricular wall, trapping epicardium in its core. This folding septum develops as the horizontal septum in reptiles and the anterior part of the interventricular septum in the other taxa. The mechanism of folding is confirmed using DiI tattoos of the ventricular surface. Trapping of epicardium-derived cells is studied by transplanting embryonic quail pro-epicardial organ into chicken hosts. The effect of decreased epicardium involvement is studied in knock-out mice, and pro-epicardium ablated chicken, resulting in diminished and even absent septum formation. Proper folding followed by diminished ventricular fusion may explain the deep interventricular cleft observed in elephants. The vertical septum, although indistinct in most reptiles except in crocodilians and pythonidsis apparently homologous to the inlet septum. Eventually the various septal components merge to form the completely septated heart. In our attempt to discover homologies between the various septum components we aim to elucidate the

Knock out for subthreshold pion production

International Nuclear Information System (INIS)

Guet, C.; Prakash, M.

1984-05-01

The contribution of nucleon-nucleon-single collisions to subthreshold pion production in hadron-nucleus and nucleus-nucleus collisions, Esub(Lab) < 300 A MeV is investigated within a knock-out type model. This contribution might be important for energies higher than about 150 MeV/nucleon but decrease strongly with decreasing beam energy

Expression of Id2 in the Second Heart Field and Cardiac Defects in Id2 Knock-Out Mice

NARCIS (Netherlands)

Jongbloed, M. R. M.; Vicente-Steijn, R.; Douglas, Y. L.; Wisse, L. J.; Mori, K.; Yokota, Y.; Bartelings, M. M.; Schalij, M. J.; Mahtab, E. A.; Poelmann, R. E.; Gittenberger-De Groot, A. C.

2011-01-01

The inhibitor of differentiation Id2 is expressed in mesoderm of the second heart field, which contributes myocardial and mesenchymal cells to the primary heart tube. The role of Id2 in cardiac development is insufficiently known. Heart development was studied in sequential developmental stages in

Post-irradiation studies on knock-out and pseudo-recoil releases of fission products from fissioning UO2

International Nuclear Information System (INIS)

Yamagishi, S.; Tanifuji, T.

1976-01-01

By using post-irradiation techniques, in-pile releases of 133 Xe, sup(85m)Kr, 88 Kr, 87 Kr and 138 Xe from UO 2 fissioning at low temperatures below about 200 0 C are studied: these are analyzed into a time-dependent knock-out and time-independent pseudo-recoil releases. For the latter, a 'self knock-out' mechanism is proposed: when a fission fragment loses thoroughly its energy near the UO 2 surface and stops there, it will knock out the surface substances and accordingly the fragment (i.e. the fission product) will be released. The effective thickness of the layer where the self knock-out occurs is found to be approximately 7A. As for the knock-out release, the following is estimated from its dependence on various factors: the knock-out release of fission products occurs from the surface layer with the effective thickness of approximately 20A: the shape of UO 2 matrix knocked out by one fission fragment passing through the surface is equivalent to a cylinder approximately 32A diameter by approximately 27A thick, (i.e. the knock-out coefficient for UO 2 is approximately 660 uranium atoms per knock-out event). On the basis of the above estimations, the conclusions derived from the past in-pile studies of fission gas releases are evaluated. (Auth.)

Simulation research on the effect of cooled EGR, supercharging and compression ratio on downsized SI engine knock

Science.gov (United States)

Shu, Gequn; Pan, Jiaying; Wei, Haiqiao; Shi, Ning

2013-03-01

Knock in spark-ignition(SI) engines severely limits engine performance and thermal efficiency. The researches on knock of downsized SI engine have mainly focused on structural design, performance optimization and advanced combustion modes, however there is little for simulation study on the effect of cooled exhaust gas recirculation(EGR) combined with downsizing technologies on SI engine performance. On the basis of mean pressure and oscillating pressure during combustion process, the effect of different levels of cooled EGR ratio, supercharging and compression ratio on engine dynamic and knock characteristic is researched with three-dimensional KIVA-3V program coupled with pressure wave equation. The cylinder pressure, combustion temperature, ignition delay timing, combustion duration, maximum mean pressure, and maximum oscillating pressure at different initial conditions are discussed and analyzed to investigate potential approaches to inhibiting engine knock while improving power output. The calculation results of the effect of just cooled EGR on knock characteristic show that appropriate levels of cooled EGR ratio can effectively suppress cylinder high-frequency pressure oscillations without obvious decrease in mean pressure. Analysis of the synergistic effect of cooled EGR, supercharging and compression ratio on knock characteristic indicates that under the condition of high supercharging and compression ratio, several times more cooled EGR ratio than that under the original condition is necessarily utilized to suppress knock occurrence effectively. The proposed method of synergistic effect of cooled EGR and downsizing technologies on knock characteristic, analyzed from the aspects of mean pressure and oscillating pressure, is an effective way to study downsized SI engine knock and provides knock inhibition approaches in practical engineering.

A human pericardium biopolymeric scaffold for autologous heart valve tissue engineering: cellular and extracellular matrix structure and biomechanical properties in comparison with a normal aortic heart valve.

Science.gov (United States)

Straka, Frantisek; Schornik, David; Masin, Jaroslav; Filova, Elena; Mirejovsky, Tomas; Burdikova, Zuzana; Svindrych, Zdenek; Chlup, Hynek; Horny, Lukas; Daniel, Matej; Machac, Jiri; Skibová, Jelena; Pirk, Jan; Bacakova, Lucie

2018-04-01

The objective of our study was to compare the cellular and extracellular matrix (ECM) structure and the biomechanical properties of human pericardium (HP) with the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV samples (from 5 patients) were harvested during heart surgery. The main cells in HP were pericardial interstitial cells, which are fibroblast-like cells of mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The ECM of HP had a statistically significantly (p structures of the two tissues, the dense part of fibrous HP (49 ± 2%) and the lamina fibrosa of NAV (47 ± 4%), was similar. In both tissues, the secant elastic modulus (Es) was significantly lower in the transversal direction (p structure and has the biomechanical properties required for a tissue from which an autologous heart valve replacement may be constructed.

Frequency domain analysis of knock images

Science.gov (United States)

Qi, Yunliang; He, Xin; Wang, Zhi; Wang, Jianxin

2014-12-01

High speed imaging-based knock analysis has mainly focused on time domain information, e.g. the spark triggered flame speed, the time when end gas auto-ignition occurs and the end gas flame speed after auto-ignition. This study presents a frequency domain analysis on the knock images recorded using a high speed camera with direct photography in a rapid compression machine (RCM). To clearly visualize the pressure wave oscillation in the combustion chamber, the images were high-pass-filtered to extract the luminosity oscillation. The luminosity spectrum was then obtained by applying fast Fourier transform (FFT) to three basic colour components (red, green and blue) of the high-pass-filtered images. Compared to the pressure spectrum, the luminosity spectra better identify the resonant modes of pressure wave oscillation. More importantly, the resonant mode shapes can be clearly visualized by reconstructing the images based on the amplitudes of luminosity spectra at the corresponding resonant frequencies, which agree well with the analytical solutions for mode shapes of gas vibration in a cylindrical cavity.

Heart Valve Diseases

Science.gov (United States)

Your heart has four valves. Normally, these valves open to let blood flow through or out of your heart, and then shut to keep it from flowing ... close tightly. It's one of the most common heart valve conditions. Sometimes it causes regurgitation. Stenosis - when ...

Prognostic significance of hemoglobin level in patients with congestive heart failure and normal ejection fraction.

Science.gov (United States)

Varadarajan, Padmini; Gandhi, Siddharth; Sharma, Sanjay; Umakanthan, Branavan; Pai, Ramdas G

2006-10-01

Previous studies have shown low hemoglobin (Hb) to have an adverse effect on survival in patients with congestive heart failure (CHF) and reduced left ventricular (LV) ejection fraction (EF); but its effect on survival in patients with CHF and normal EF is not known. This study sought to determine whether low Hb has an effect on survival in patients with both CHF and normal EF. Detailed chart reviews were performed by medical residents on 2,246 patients (48% with normal EF) with a discharge diagnosis of CHF in a large tertiary care hospital from 1990 to 1999. The CHF diagnosis was validated using the Framingham criteria. Mortality data were obtained from the National Death Index. Survival analysis was performed using Kaplan-Meier and Cox regression models. By Kaplan-Meier analysis, low Hb (< 12 gm/dl) compared with normal hemoglobin was associated with a lower 5-year survival in patients with CHF and both normal (38 vs. 50%, p = 0.0008) and reduced (35 vs. 48%, p = 0.0009) EF. Using the Cox regression model, low Hb was an independent predictor of mortality after adjusting for age, gender, renal dysfunction, diabetes mellitus, hypertension, and EF in both groups of patients. Low Hb has an independent adverse effect on survival in patients with CHF and both normal and reduced EF in both groups of patients.

Knock-on accident prevention in a chemical cluster

NARCIS (Netherlands)

Reniers, Genserik L L; Dullaert, W.

Empirical research has revealed that safety managers acknowledge the importance of cross-company cooperation for knock-on risk reduction. This paper presents a decision support software tool, called DomPrevPlanning

In vitro cultured progenitors and precursors of cardiac cell lineages from human normal and post-ischemic hearts

Directory of Open Access Journals (Sweden)

F Di Meglio

2009-08-01

Full Text Available The demonstration of the presence of dividing primitive cells in damaged hearts has sparked increased interest about myocardium regenerative processes. We examined the rate and the differentiation of in vitro cultured resident cardiac primitive cells obtained from pathological and normal human hearts in order to evaluate the activation of progenitors and precursors of cardiac cell lineages in post-ischemic human hearts. The precursors and progenitors of cardiomyocyte, smooth muscle and endothelial lineage were identified by immunocytochemistry and the expression of characteristic markers was studied by western blot and RT-PCR. The amount of proteins characteristic for cardiac cells (a-SA and MHC, VEGFR-2 and FVIII, SMA for the precursors of cardiomyocytes, endothelial and smooth muscle cells, respectively inclines toward an increase in both a-SA and MHC. The increased levels of FVIII and VEGFR2 are statistically significant, suggesting an important re-activation of neoangiogenesis. At the same time, the augmented expression of mRNA for Nkx 2.5, the trascriptional factor for cardiomyocyte differentiation, confirms the persistence of differentiative processes in terminally injured hearts. Our study would appear to confirm the activation of human heart regeneration potential in pathological conditions and the ability of its primitive cells to maintain their proliferative capability in vitro. The cardiac cell isolation method we used could be useful in the future for studying modifications to the microenvironment that positively influence cardiac primitive cell differentiation or inhibit, or retard, the pathological remodeling and functional degradation of the heart.

Knocking in an Internal-combustion Engine

Science.gov (United States)

Sokolik, A; Voinov, A

1940-01-01

The question remains open of the relation between the phenomena of knocking in the engine and the explosion wave. The solution of this problem is the object of this paper. The tests were conducted on an aircraft engine with a pyrex glass window in the cylinder head. Photographs were then taken of various combinations of fuels and conditions.

Highly efficient CRISPR/HDR-mediated knock-in for mouse embryonic stem cells and zygotes.

Science.gov (United States)

Wang, Bangmei; Li, Kunyu; Wang, Amy; Reiser, Michelle; Saunders, Thom; Lockey, Richard F; Wang, Jia-Wang

2015-10-01

The clustered regularly interspaced short palindromic repeat (CRISPR) gene editing technique, based on the non-homologous end-joining (NHEJ) repair pathway, has been used to generate gene knock-outs with variable sizes of small insertion/deletions with high efficiency. More precise genome editing, either the insertion or deletion of a desired fragment, can be done by combining the homology-directed-repair (HDR) pathway with CRISPR cleavage. However, HDR-mediated gene knock-in experiments are typically inefficient, and there have been no reports of successful gene knock-in with DNA fragments larger than 4 kb. Here, we describe the targeted insertion of large DNA fragments (7.4 and 5.8 kb) into the genomes of mouse embryonic stem (ES) cells and zygotes, respectively, using the CRISPR/HDR technique without NHEJ inhibitors. Our data show that CRISPR/HDR without NHEJ inhibitors can result in highly efficient gene knock-in, equivalent to CRISPR/HDR with NHEJ inhibitors. Although NHEJ is the dominant repair pathway associated with CRISPR-mediated double-strand breaks (DSBs), and biallelic gene knock-ins are common, NHEJ and biallelic gene knock-ins were not detected. Our results demonstrate that efficient targeted insertion of large DNA fragments without NHEJ inhibitors is possible, a result that should stimulate interest in understanding the mechanisms of high efficiency CRISPR targeting in general.

Autophagy and UPR in alpha-crystallin mutant knock-in mouse models of hereditary cataracts.

Science.gov (United States)

Andley, Usha P; Goldman, Joshua W

2016-01-01

Knock-in mice provide useful models of congenital and age-related cataracts caused by α-crystallin mutations. R49C αA-crystallin and R120G αB-crystallin mutations are linked with hereditary cataracts. Knock-in αA-R49C+/- heterozygotes develop cataracts by 1-2months, whereas homozygote mice have cataracts at birth. The R49C mutation drastically reduces lens protein water solubility and causes cell death in knock-in mouse lenses. Mutant crystallin cannot function as a chaperone, which leads to protein aggregation and lens opacity. Protein aggregation disrupts the lens fiber cell structure and normal development and causes cell death in epithelial and fiber cells. We determined what aspects of the wild-type phenotype are age-dependently altered in the mutant lens. Wild-type, heterozygote (αA-R49C+/-), and homozygote (αA-R49C+/+) mouse lenses were assessed pre- and postnatally for lens morphology (electron microscopy, immunohistochemistry), and autophagy or unfolded protein response markers (immunoblotting). Morphology was altered by embryonic day 17 in R49C+/+ lenses; R49C+/- lens morphology was unaffected at this stage. Active autophagy in the lens epithelium of mutant lenses was indicated by the presence of autophagosomes using electron microscopy. Protein p62 levels, which are degraded specifically by autophagy, increased in αA-R49C mutant versus wild-type lenses, suggesting autophagy inhibition in the mutant lenses. The unfolded protein response marker XBP-1 was upregulated in adult lenses of αB-R120G+/+ mice, suggesting its role in lens opacification. Mutated crystallins alter lens morphology, autophagy, and stress responses. Therapeutic modulation of autophagic pathways may improve protein degradation in cataractous lenses and reduce lens opacity. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Low Left Atrial Compliance Contributes to the Clinical Recurrence of Atrial Fibrillation after Catheter Ablation in Patients with Structurally and Functionally Normal Heart.

Science.gov (United States)

Park, Junbeom; Yang, Pil-sung; Kim, Tae-Hoon; Uhm, Jae-Sun; Kim, Joung-Youn; Joung, Boyoung; Lee, Moon-Hyoung; Hwang, Chun; Pak, Hui-Nam

2015-01-01

Stiff left atrial (LA) syndrome was initially reported in post-cardiac surgery patients and known to be associated with low LA compliance. We investigated the physiological and clinical implications of LA compliance by estimating LA pulse pressure (LApp) among patients with atrial fibrillation (AF) and structurally and functionally normal heart. Among 1038 consecutive patients with LA pressure measurements before AF ablation, we included 334 patients with structurally and functionally normal heart (81.7% male, 54.1±10.6 years, 77.0% paroxysmal AF) after excluding those with hypertension, diabetes, and previous ablation or cardiac surgery. We measured LApp (peak-nadir LA pressure) at the beginning of the ablation procedure and compared the values with clinical parameters and the AF recurrence rate. AF patients with normal heart were younger and more frequently male and had paroxysmal AF, a lower body mass index, and a lower LApp compared to others (all p<0.05). Based on the median value, the low LA compliance group (LApp≥13 mmHg) had a smaller LA volume index and lower LA voltage (all p<0.05) compared to the high LA compliance group. During a mean follow-up of 16.7±11.8 months, low LA compliance was independently associated with two fold-higher risk of clinical AF recurrence (HR:2.202; 95%CI:1.077-4.503; p = 0.031). Low LA compliance, as determined by an elevated LApp, was associated with a smaller LA volume index and lower LA voltage and independently associated with higher clinical recurrence after catheter ablation in AF patients with structurally and functionally normal heart.

[RS-1 enhanced the efficiency of CRISPR-Cas9 mediated knock-in of human lactoferrin].

Science.gov (United States)

Zhou, Wenjun; Guo, Rihong; Deng, Mingtian; Wang, Feng; Zhang, Yanli

2017-08-25

This study aims to knock out the goat β-lactoglobulin (BLG) gene using CRISPR-Cas9 system and knock in human lactoferrin (hLF) at the BLG locus, and further study the effect of RAD51 stimulatory compound (RS-1) on homologous recombination efficiency. First, we designed an sgRNA targeting the first exon of goat BLG gene and constructed a co-expression vector pCas9-sgBLG. This sgRNA vector was then transfected into goat ear fibroblasts (GEFs), and the target region was examined by T7EN1 assay and sequencing. Second, we constructed a targeting vector pBHA-hLF-NIE including NEO and EGFP genes based on BLG gene locus. This targeting vector together with pCas9-sgBLG expression vector was co-transfected into GEFs. Transfected cells were then treated with 0, 5, 10 and 20 μmol/L RS-1 for 72 h to analyse the EGFP expression efficiency. Next, we used 800 μg/mL G418 to screen G418-resistent cell clones, and studied hLF site-specific knock-in cell clones by PCR and sequencing. The editing efficiency of sgBLG was between 25% and 31%. The EGFP expression efficiency indicated that the gene knock-in efficiency was improved by RS-1 in a dose-dependent manner, which could reach 3.5-fold compared to the control group. The percentage of positive cells with hLF knock-in was increased to 32.61% when 10 μmol/L RS-1 was used. However, when the concentration of RS-1 increased to 20 μmol/L, the percentage of positive cells decreased to 22.22% and resulted in an increase of senescent cell clone number. These results suggested that hLF knock-in and BLG knock-out in GEFs were achieved by using CRISPR/Cas9 system, and optimum concentration of RS-1 could improve knock-in efficiency, which provides a reference for efficiently obtaining gene knock-in cells using CRISPR/Cas9 in the future.

Evaluation of Anti-Knock Quality of Dicyclopentadiene-Gasoline Blends

KAUST Repository

Al-Khodaier, Mohannad

2017-03-28

Increasing the anti-knock quality of gasoline fuels can enable higher efficiency in spark ignition engines. In this study, the blending anti-knock quality of dicyclopentadiene (DCPD), a by-product of ethylene production from naphtha cracking, with various gasoline fuels is explored. The blends were tested in an ignition quality tester (IQT) and a modified cooperative fuel research (CFR) engine operating under homogenous charge compression ignition (HCCI) and knock limited spark advance (KLSA) conditions. Due to current fuel regulations, ethanol is widely used as a gasoline blending component in many markets. In addition, ethanol is widely used as a fuel and literature verifying its performance. Moreover, because ethanol exhibits synergistic effects, the test results of DCPD-gasoline blends were compared to those of ethanol-gasoline blends. The experiments conducted in this work enabled the screening of DCPD auto-ignition characteristics across a range of combustion modes. The synergistic blending nature of DCPD was apparent and appeared to be greater than that of ethanol. The data presented suggests that DCPD has the potential to be a high octane blending component in gasoline; one which can substitute alkylates, isomerates, reformates, and oxygenates.

Evaluation of Anti-Knock Quality of Dicyclopentadiene-Gasoline Blends

KAUST Repository

Al-Khodaier, Mohannad; Bhavani Shankar, Vijai Shankar; Waqas, Muhammad; Naser, Nimal; Sarathy, Mani; Johansson, Bengt

2017-01-01

Increasing the anti-knock quality of gasoline fuels can enable higher efficiency in spark ignition engines. In this study, the blending anti-knock quality of dicyclopentadiene (DCPD), a by-product of ethylene production from naphtha cracking, with various gasoline fuels is explored. The blends were tested in an ignition quality tester (IQT) and a modified cooperative fuel research (CFR) engine operating under homogenous charge compression ignition (HCCI) and knock limited spark advance (KLSA) conditions. Due to current fuel regulations, ethanol is widely used as a gasoline blending component in many markets. In addition, ethanol is widely used as a fuel and literature verifying its performance. Moreover, because ethanol exhibits synergistic effects, the test results of DCPD-gasoline blends were compared to those of ethanol-gasoline blends. The experiments conducted in this work enabled the screening of DCPD auto-ignition characteristics across a range of combustion modes. The synergistic blending nature of DCPD was apparent and appeared to be greater than that of ethanol. The data presented suggests that DCPD has the potential to be a high octane blending component in gasoline; one which can substitute alkylates, isomerates, reformates, and oxygenates.

Blood pressure and heart rate variability analysis of orthostatic challenge in normal human pregnancies.

Science.gov (United States)

Heiskanen, Nonna; Saarelainen, Heli; Valtonen, Pirjo; Lyyra-Laitinen, Tiina; Laitinen, Tomi; Vanninen, Esko; Heinonen, Seppo

2008-11-01

The aim of the present study was to evaluate pregnancy-related changes in autonomic regulatory functions in healthy subjects. We studied cardiovascular autonomic responses to head-up tilt (HUT) in 28 pregnant women during the third trimester of pregnancy and 3 months after parturition. The maternal ECG and non-invasive beat-to-beat blood pressure were recorded in the horizontal position (left-lateral position) and during HUT in the upright position. Stroke volume was assessed from blood pressure signal by using the arterial pulse contour method. Heart rate variability (HRV) was analysed in frequency domain, and baroreflex sensitivity by the cross-spectral and the sequence methods. In the horizontal position, all frequency components of HRV were lower during pregnancy than 3 months after parturition (P pregnancy had no influence on normalized low frequency and high frequency powers. During pregnancy haemodynamics was well balanced with only minor changes in response to postural change while haemodynamic responses to HUT were more remarkable after parturition. In pregnant women HRV and especially its very low frequency component increased in response to HUT, whereas at 3 months after parturition the direction of these changes was opposite. Parasympathetic deactivation towards term is likely to contribute to increased heart rate and cardiac output at rest, whereas restored sympathetic modulation with modest responses may contribute stable peripheral resistance and sufficient placental blood supply under stimulated conditions. It is important to understand cardiovascular autonomic nervous system and haemodynamic control in normal pregnancy before being able to judge whether they are dysregulated in complicated pregnancies.

Generation of an allelic series of knock-in mice using recombinase-mediated cassette exchange (RMCE).

Science.gov (United States)

Roebroek, Anton J M; Van Gool, Bart

2014-01-01

Molecular genetic strategies applying embryonic stem cell (ES cell) technologies to study the function of a gene in mice or to generate a mouse model for a human disease are continuously under development. Next to (conditional) inactivation of genes the application and importance of approaches to generate knock-in mutations are increasing. In this chapter the principle and application of recombinase-mediated cassette exchange (RMCE) are discussed as being a new emerging knock-in strategy, which enables easy generation of a series of different knock-in mutations within one gene. An RMCE protocol, which was used to generate a series of different knock-in mutations in the Lrp1 gene of ES cells, is described in detail as an example of how RMCE can be used to generate highly efficiently an allelic series of differently modified ES cell clones from a parental modified ES cell clone. Subsequently the differently modified ES cell clones can be used to generate an allelic series of mutant knock-in mice.

Non-invasive estimation of myocardial efficiency using positron emission tomography and carbon-11 acetate - comparison between the normal and failing human heart

International Nuclear Information System (INIS)

Bengel, F.M.; Nekolla, S.; Schwaiger, M.; Ungerer, M.

2000-01-01

We studied ten patients with idiopathic dilated cardiomyopathy (DCM) and 11 healthy normals by dynamic PET with 11 C-acetate and either tomographic radionuclide ventriculography or cine magnetic resonance imaging. A ''stroke work index'' (SWI) was calculated by: SWI = systolic blood pressure x stroke volume/body surface area. To estimate myocardial efficiency, a ''work-metabolic index'' (WMI) was then obtained as follows: WMI = SWI x heart rate/k(mono), where k(mono) is the washout constant for 11 C-acetate derived from mono-exponential fitting. In DCM patients, left ventricular ejection fraction was 19%±10% and end-diastolic volume was 92±28 ml/m 2 (vs 64%±7% and 55±8 ml/m 2 in normals, P 2 ; P 6 mmHg x ml/m 2 ; P<0.001) were lower in DCM patients, too. Overall, the WMI correlated positively with ejection parameters (r=0.73, P<0.001 for ejection fraction; r=0.93, P<0.001 for stroke volume), and inversely with systemic vascular resistance (r=-0.77; P<0.001). There was a weak positive correlation between WMI and end-diastolic volume in normals (r=0.45; P=0.17), while in DCM patients, a non-significant negative correlation coefficient (r=-0.21; P=0.57) was obtained. In conclusion non-invasive estimates of oxygen consumption and efficiency in the failing heart were reduced compared with those in normals. Estimates of efficiency increased with increasing contractile performance, and decreased with increasing ventricular afterload. In contrast to normals, the failing heart was not able to respond with an increase in efficiency to increasing ventricular volume.(orig./MG) (orig.)

Hearts of dystonia musculorum mice display normal morphological and histological features but show signs of cardiac stress.

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Justin G Boyer

2010-03-01

Full Text Available Dystonin is a giant cytoskeletal protein belonging to the plakin protein family and is believed to crosslink the major filament systems in contractile cells. Previous work has demonstrated skeletal muscle defects in dystonin-deficient dystonia musculorum (dt mice. In this study, we show that the dystonin muscle isoform is localized at the Z-disc, the H zone, the sarcolemma and intercalated discs in cardiac tissue. Based on this localization pattern, we tested whether dystonin-deficiency leads to structural defects in cardiac muscle. Desmin intermediate filament, microfilament, and microtubule subcellular organization appeared normal in dt hearts. Nevertheless, increased transcript levels of atrial natriuretic factor (ANF, 66% beta-myosin heavy chain (beta-MHC, 95% and decreased levels of sarcoplasmic reticulum calcium pump isoform 2A (SERCA2a, 26%, all signs of cardiac muscle stress, were noted in dt hearts. Hearts from two-week old dt mice were assessed for the presence of morphological and histological alterations. Heart to body weight ratios as well as left ventricular wall thickness and left chamber volume measurements were similar between dt and wild-type control mice. Hearts from dt mice also displayed no signs of fibrosis or calcification. Taken together, our data provide new insights into the intricate structure of the sarcomere by situating dystonin in cardiac muscle fibers and suggest that dystonin does not significantly influence the structural organization of cardiac muscle fibers during early postnatal development.

Hyperactivity of newborn Pten knock-out neurons results from increased excitatory synaptic drive.

Science.gov (United States)

Williams, Michael R; DeSpenza, Tyrone; Li, Meijie; Gulledge, Allan T; Luikart, Bryan W

2015-01-21

Developing neurons must regulate morphology, intrinsic excitability, and synaptogenesis to form neural circuits. When these processes go awry, disorders, including autism spectrum disorder (ASD) or epilepsy, may result. The phosphatase Pten is mutated in some patients having ASD and seizures, suggesting that its mutation disrupts neurological function in part through increasing neuronal activity. Supporting this idea, neuronal knock-out of Pten in mice can cause macrocephaly, behavioral changes similar to ASD, and seizures. However, the mechanisms through which excitability is enhanced following Pten depletion are unclear. Previous studies have separately shown that Pten-depleted neurons can drive seizures, receive elevated excitatory synaptic input, and have abnormal dendrites. We therefore tested the hypothesis that developing Pten-depleted neurons are hyperactive due to increased excitatory synaptogenesis using electrophysiology, calcium imaging, morphological analyses, and modeling. This was accomplished by coinjecting retroviruses to either "birthdate" or birthdate and knock-out Pten in granule neurons of the murine neonatal dentate gyrus. We found that Pten knock-out neurons, despite a rapid onset of hypertrophy, were more active in vivo. Pten knock-out neurons fired at more hyperpolarized membrane potentials, displayed greater peak spike rates, and were more sensitive to depolarizing synaptic input. The increased sensitivity of Pten knock-out neurons was due, in part, to a higher density of synapses located more proximal to the soma. We determined that increased synaptic drive was sufficient to drive hypertrophic Pten knock-out neurons beyond their altered action potential threshold. Thus, our work contributes a developmental mechanism for the increased activity of Pten-depleted neurons. Copyright © 2015 the authors 0270-6474/15/350943-17$15.00/0.

Effects of Hyponatremia Normalization on the Short-Term Mortality and Rehospitalizations in Patients with Recent Acute Decompensated Heart Failure: A Retrospective Study

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Renato De Vecchis

2016-10-01

Full Text Available Background: Several studies have shown that hyponatremia is associated with increased risk of rehospitalization and death in patients with heart failure. In these studies, chronic heart failure (CHF patients with persistent hyponatremia were compared only with CHF patients with a normal sodium level at hospital admission. Aims: In the present retrospective study, conducted in a cohort of patients with recent acute decompensated heart failure (ADHF, all with hyponatremia ascertained at the time of hospital admission, we aimed to evaluate the effect of the normalization of serum sodium on the composite endpoint of short-term rehospitalization and mortality. Methods: A retrospective study centered on medical records of patients hospitalized for ADHF in the period April 2013 to April 2016 was performed. Data regarding serum sodium measurements had to be collected from medical records of cardiology wards of two hospitals, and were then processed for statistical analysis. As an inclusion criterion for enrollment, patients had to be suffering from heart failure that had required at least one hospitalization. Moreover, they had to be suffering from a state of hyponatremia (serum sodium < 135 mEq/L at admission on the occasion of the index hospitalization. Patients with hyponatremia at admission were divided into two groups, one comprising patients with hyponatremia that persisted at the time of discharge (persistent hyponatremia and a second including patients who had achieved normalization of their serum sodium levels (serum Na+ ≥ 135 mEq/L during hospitalization until discharge. For both groups, the risk of mortality and rehospitalization during a 30-day follow-up was assessed. Results: One hundred and sixty CHF patients with various degrees of functional impairment were enrolled in the study. Among them, 56 (35% had persistent hyponatremia over the course of hospitalization. At multivariable Cox proportional-hazards regression analysis, the risk of

Knocking Down Snrnp200 Initiates Demorphogenesis of Rod Photoreceptors in Zebrafish

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Yuan Liu

2015-01-01

Full Text Available Purpose. The small nuclear ribonucleoprotein 200 kDa (SNRNP200 gene is a fundamental component for precursor message RNA (pre-mRNA splicing and has been implicated in the etiology of autosomal dominant retinitis pigmentosa (adRP. This study aims to determine the consequences of knocking down Snrnp200 in zebrafish. Methods. Expression of the Snrnp200 transcript in zebrafish was determined via whole mount in situ hybridization. Morpholino oligonucleotide (MO aiming to knock down the expression of Snrnp200 was injected into zebrafish embryos, followed by analyses of aberrant splicing and expression of the U4/U6-U5 tri-small nuclear ribonucleoproteins (snRNPs components and retina-specific transcripts. Systemic changes and retinal phenotypes were further characterized by histological study and immunofluorescence staining. Results. Snrnp200 was ubiquitously expressed in zebrafish. Knocking down Snrnp200 in zebrafish triggered aberrant splicing of the cbln1 gene, upregulation of other U4/U6-U5 tri-snRNP components, and downregulation of a panel of retina-specific transcripts. Systemic defects were found correlated with knockdown of Snrnp200 in zebrafish. Only demorphogenesis of rod photoreceptors was detected in the initial stage, mimicking the disease characteristics of RP. Conclusions. We conclude that knocking down Snrnp200 in zebrafish could alter regular splicing and expression of a panel of genes, which may eventually trigger rod defects.

Effects of Heat of Vaporization and Octane Sensitivity on Knock-Limited Spark Ignition Engine Performance

Energy Technology Data Exchange (ETDEWEB)

Ratcliff, Matthew A [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Burton, Jonathan L [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Sindler, Petr [National Renewable Energy Laboratory (NREL), Golden, CO (United States); McCormick, Robert L [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Christensen, Earl D [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Fouts, Lisa A [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

2018-04-03

Knock-limited loads for a set of surrogate gasolines all having nominal 100 research octane number (RON), approximately 11 octane sensitivity (S), and a heat of vaporization (HOV) range of 390 to 595 kJ/kg at 25 degrees C were investigated. A single-cylinder spark-ignition engine derived from a General Motors Ecotec direct injection (DI) engine was used to perform load sweeps at a fixed intake air temperature (IAT) of 50 degrees C, as well as knock-limited load measurements across a range of IATs up to 90 degrees C. Both DI and pre-vaporized fuel (supplied by a fuel injector mounted far upstream of the intake valves and heated intake runner walls) experiments were performed to separate the chemical and thermal effects of the fuels' knock resistance. The DI load sweeps at 50 degrees C intake air temperature showed no effect of HOV on the knock-limited performance. The data suggest that HOV acts as a thermal contributor to S under the conditions studied. Measurement of knock-limited loads from the IAT sweeps for DI at late combustion phasing showed that a 40 vol% ethanol (E40) blend provided additional knock resistance at the highest temperatures, compared to a 20 vol% ethanol blend and hydrocarbon fuel with similar RON and S. Using the pre-vaporized fuel system, all the high S fuels produced nearly identical knock-limited loads at each temperature across the range of IATs studied. For these fuels RON ranged from 99.2 to 101.1 and S ranged from 9.4 to 12.2, with E40 having the lowest RON and highest S. The higher knock-limited loads for E40 at the highest IATs examined were consistent with the slightly higher S for this fuel, and the lower engine operating condition K values arising from use of this fuel. The study highlights how fuel HOV can affect the temperature at intake valve closing, and consequently the pressure-temperature history of the end gas leading to more negative values of K, thereby enhancing the effect of S on knock resistance.

Determination of knock characteristics in spark ignition engines: an approach based on ensemble empirical mode decomposition

International Nuclear Information System (INIS)

Li, Ning; Liang, Caiping; Yang, Jianguo; Zhou, Rui

2016-01-01

Knock is one of the major constraints to improve the performance and thermal efficiency of spark ignition (SI) engines. It can also result in severe permanent engine damage under certain operating conditions. Based on the ensemble empirical mode decomposition (EEMD), this paper proposes a new approach to determine the knock characteristics in SI engines. By adding a uniformly distributed and finite white Gaussian noise, the EEMD can preserve signal continuity in different scales and therefore alleviates the mode-mixing problem occurring in the classic empirical mode decomposition (EMD). The feasibilities of applying the EEMD to detect the knock signatures of a test SI engine via the pressure signal measured from combustion chamber and the vibration signal measured from cylinder head are investigated. Experimental results show that the EEMD-based method is able to detect the knock signatures from both the pressure signal and vibration signal, even in initial stage of knock. Finally, by comparing the application results with those obtained by short-time Fourier transform (STFT), Wigner–Ville distribution (WVD) and discrete wavelet transform (DWT), the superiority of the EEMD method in determining knock characteristics is demonstrated. (paper)

MMEJ-assisted gene knock-in using TALENs and CRISPR-Cas9 with the PITCh systems.

Science.gov (United States)

Sakuma, Tetsushi; Nakade, Shota; Sakane, Yuto; Suzuki, Ken-Ichi T; Yamamoto, Takashi

2016-01-01

Programmable nucleases enable engineering of the genome by utilizing endogenous DNA double-strand break (DSB) repair pathways. Although homologous recombination (HR)-mediated gene knock-in is well established, it cannot necessarily be applied in every cell type and organism because of variable HR frequencies. We recently reported an alternative method of gene knock-in, named the PITCh (Precise Integration into Target Chromosome) system, assisted by microhomology-mediated end-joining (MMEJ). MMEJ harnesses independent machinery from HR, and it requires an extremely short homologous sequence (5-25 bp) for DSB repair, resulting in precise gene knock-in with a more easily constructed donor vector. Here we describe a streamlined protocol for PITCh knock-in, including the design and construction of the PITCh vectors, and their delivery to either human cell lines by transfection or to frog embryos by microinjection. The construction of the PITCh vectors requires only a few days, and the entire process takes ∼ 1.5 months to establish knocked-in cells or ∼ 1 week from injection to early genotyping in frog embryos.

Quantitative assessment of thallium myocardial washout rate: Importance of peak heart rate and lung thallium uptake in defining normal values

International Nuclear Information System (INIS)

Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kohei; Kozuka, Takahiro; Saito, Muneyasu; Sumiyoshi, Tetsuya; National Cardiovascular Center, Suita, Osaka

1987-01-01

Traditionally, the results of exercise thallium scintigraphy were interpreted by transient defect analysis using initial and delayed images. Recently, washout rate analysis has been used for the relative quantification of exercise thallium scintigraphy. A diffuse slow washout from all myocardial regions has been defined as the indicator of extensive coronary artery disease. However, slow washout has occasionally been observed in normal cases and in healthy myocardial segments which are not supplied by a stenosed artery in patients with single or double vessel disease. We evaluate the factors influencing washout rate in 100 normal patients and 63 patients with angina pectoris (33 cases of single vessel disease and 30 cases of double vessel disease). The washout rates were calculated using circumferential profile analysis. In normal patients, washout rate was closely related to peak heart rate (r=0.72) and inversely related to lung thallium uptake (r=-0.56). A diffuse slow washout was observed in seven (7%) of 100 normal patients, six (18%) of 33 cases of single vessel disease and eight (24%) of 30 cases of double vessel disease. The patients with diffuse slow washout showed significantly higher lung thallium uptake values and lower peak heart rates than those without diffuse slow washout (P<0.01). Thus, this false positive slow washout should be considered in the interpretation of quantitative exercise thallium scintigraphy. (orig.)

Analysis of knocking combustion with the aid of pressure sensors; Einsatz von Drucksensoren zur Beurteilung klopfender Verbrennung

Energy Technology Data Exchange (ETDEWEB)

Stadler, J.; Walter, T. [Kistler AG, Winterthur (Switzerland); Bertola, A.; Wolfer, P.; Hoewing, J. [Kistler Instrumente GmbH, Ostfildern (Germany); Gossweiler, C. [Fachhochschule Nordwestschweiz (Switzerland). ITFE; Rothe, M.; Spicher, U. [Karlsruhe Univ. (T.H.) (Germany). Inst. fuer Kolbenmaschinen

2006-07-01

Depending on its frequency and intensity, knocking combustion can cause engine damage due to excessive thermal or mechanical stress on components. During knocking combustion, the cylinder pressure signal is overlaid with high-frequency pressure oscillations. Reliable detection of the knock timing and quantification of the knock intensity based on local measurement of the cylinder pressure demand for particular care, especially when it comes to selecting and adapting the sensor technology and also during the evaluation process using customary knock analysis methods. This publication examines various types of cylinder pressure sensors, how they are installed in the combustion chamber, the effect of sensor positioning and assesses them with regard to accuracy. Finally, on the basis of the test results, recommendations are given for selecting sensors and adapting them within the combustion chamber. A crucial factor for pressure measurement during knocking combustion is the sensor position within the combustion chamber. The sensor type is of secondary importance; at most, cavities between the combustion chamber and the sensor may influence the measuring signal. To assess the sensitivity of the knock evaluation algorithms to various mounting positions and sensor types, it is advisable to carry out comparative measurements between different sensor positions and the measuring spark plug. (orig.)

A kinase-dead knock-in mutation in mTOR leads to early embryonic lethality and is dispensable for the immune system in heterozygous mice

Directory of Open Access Journals (Sweden)

Cavender Druie

2009-05-01

Full Text Available Abstract Background The mammalian target of rapamycin protein (mTOR is an evolutionarily conserved kinase that regulates protein synthesis, cell cycle progression and proliferation in response to various environmental cues. As a critical downstream mediator of PI3K signaling, mTOR is important for lymphocyte development and function of mature T and B-cells. Most studies of mTOR in immune responses have relied on the use of pharmacological inhibitors, such as rapamycin. Rapamycin-FKBP12 complex exerts its immunosuppressive and anti-proliferative effect by binding outside the kinase domain of mTOR, and subsequently inhibiting downstream mTOR signaling. Results To determine the requirement for mTOR kinase activity in the immune system function, we generated knock-in mice carrying a mutation (D2338 in the catalytic domain of mTOR. While homozygous mTOR kd/kd embryos died before embryonic day 6.5, heterozygous mTOR+/kd mice appeared entirely normal and are fertile. mTOR +/kd mice exhibited normal T and B cell development and unaltered proliferative responses of splenocytes to IL-2 and TCR/CD28. In addition, heterozygousity for the mTOR kinase-dead allele did not sensitize T cells to rapamycin in a CD3-mediated proliferation assay. Unexpectedly, mTOR kinase activity towards its substrate 4E-BP1 was not decreased in hearts and livers from heterozygous animals. Conclusion Altogether, our findings indicate that mTOR kinase activity is indispensable for the early development of mouse embryos. Moreover, a single wild type mTOR allele is sufficient to maintain normal postnatal growth and lymphocyte development and proliferation.

On a calculation of nucleon knock-out cross sections in a collision of relativistic nuclei

International Nuclear Information System (INIS)

Goryachev, B.I.; Lin'kova, N.V.

1985-01-01

It is shown that in the framework of the two-stage model one can obtain knock-out cross sections of the given number of nucleons from the nucleus-target at a certain number of nucleons knocked out from the nucleus-projectile. The first stage is considered as a fast process of nucleon collisions of interacting nuclei which is completed with knock out of one or several nucleons. The second stage-comparatively slow - is related to de-excitation of nuclei-fragments

Fuel effects on knock, heat releases and CARS temperatures in a spark ignition engine

NARCIS (Netherlands)

Kalghatgi, G.T.; Golombok, M.; Snowdon, P.

1995-01-01

Net heat release, knock characteristics and temperature were derived from in-cylinder pressure and end-gas CARS measurements for different fuels in a single-cylinder engine. The maximum net heat release rate resulting from the final phase of autoignition is closely associated with knock intensity.

Bex1 knock out mice show altered skeletal muscle regeneration

International Nuclear Information System (INIS)

Koo, Jae Hyung; Smiley, Mark A.; Lovering, Richard M.; Margolis, Frank L.

2007-01-01

Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca 2+ /CaM may be involved in skeletal muscle regeneration

knock characteristics analysis of a supercharged spark ignition

African Journals Online (AJOL)

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The power output of a spark ignition engine could be improved by boosting the ... that the presence of aromatics was responsible for the better anti-knock ..... System, a Master's Thesis in the Institutionen för ... Maintenance and Reliability, Vol.

A New MRI-Based Model of Heart Function with Coupled Hemodynamics and Application to Normal and Diseased Canine Left Ventricles

Science.gov (United States)

Choi, Young Joon; Constantino, Jason; Vedula, Vijay; Trayanova, Natalia; Mittal, Rajat

2015-01-01

A methodology for the simulation of heart function that combines an MRI-based model of cardiac electromechanics (CE) with a Navier–Stokes-based hemodynamics model is presented. The CE model consists of two coupled components that simulate the electrical and the mechanical functions of the heart. Accurate representations of ventricular geometry and fiber orientations are constructed from the structural magnetic resonance and the diffusion tensor MR images, respectively. The deformation of the ventricle obtained from the electromechanical model serves as input to the hemodynamics model in this one-way coupled approach via imposed kinematic wall velocity boundary conditions and at the same time, governs the blood flow into and out of the ventricular volume. The time-dependent endocardial surfaces are registered using a diffeomorphic mapping algorithm, while the intraventricular blood flow patterns are simulated using a sharp-interface immersed boundary method-based flow solver. The utility of the combined heart-function model is demonstrated by comparing the hemodynamic characteristics of a normal canine heart beating in sinus rhythm against that of the dyssynchronously beating failing heart. We also discuss the potential of coupled CE and hemodynamics models for various clinical applications. PMID:26442254

Potential fields on the ventricular surface of the exposed dog heart during normal excitation.

Science.gov (United States)

Arisi, G; Macchi, E; Baruffi, S; Spaggiari, S; Taccardi, B

1983-06-01

We studied the normal spread of excitation on the anterior and posterior ventricular surface of open-chest dogs by recording unipolar electrograms from an array of 1124 electrodes spaced 2 mm apart. The array had the shape of the ventricular surface of the heart. The electrograms were processed by a computer and displayed as epicardial equipotential maps at 1-msec intervals. Isochrone maps also were drawn. Several new features of epicardial potential fields were identified: (1) a high number of breakthrough points; (2) the topography, apparent widths, velocities of the wavefronts and the related potential drop; (3) the topography of positive potential peaks in relation to the wavefronts. Fifteen to 24 breakthrough points were located on the anterior, and 10 to 13 on the posterior ventricular surface. Some were in previously described locations and many others in new locations. Specifically, 3 to 5 breakthrough points appeared close to the atrioventricular groove on the anterior right ventricle and 2 to 4 on the posterior heart aspect; these basal breakthrough points appeared when a large portion of ventricular surface was still unexcited. Due to the presence of numerous breakthrough points on the anterior and posterior aspect of the heart which had not previously been described, the spread of excitation on the ventricular surface was "mosaic-like," with activation wavefronts spreading in all directions, rather than radially from the two breakthrough points, as traditionally described. The positive potential peaks which lay ahead of the expanding wavefronts moved along preferential directions which were probably related to the myocardial fiber direction.

On the interpretation of (e,e'p) knock-out reaction

International Nuclear Information System (INIS)

Dieperink, A.E.L.

The basic physics in (e,e'p) knock-out reactions is illustrated assuming that the knocked-out proton can be treated as a plane wave (PWIA). Corrections for distortion and absorption of the outgoing proton can, in principle, be calculated to a good approximation with an optical potential. The spectral function is characterized in terms of its energy moments, the lowest of which can be incorporated in an independent particle shell model (IPSM): occupatiomn probability (zeroth moment) and the mean removal energy (centroid energy). Deviations from IPSM are discussed: binding energy sum rule, A=3 nuclei, 6 Li, and fragmentation of single-particle strength

High-temperature expansion and knock-out properties of moulding sands with water glass

Directory of Open Access Journals (Sweden)

Major-Gabryś K.

2007-01-01

Full Text Available The article focuses on the topic of improving the knock-out properties of moulding sand with water glass and ester hardener. It is settled that the cause of worse knock-out properties of moulding sand can be brought by their thermal expansion in increased temperatures. There is a presentation of the influence of different additives, containing Al2O3, on moulding sands’ expansion in increased temperatures. Within the frames of research, there was an elaboration of the influence of authors own additive- Glassex, on the expansion phenomenon of moulding sands with water glass and ester hardener. It is concluded, that the new additive stops the expansion of moulding sands and as well it improves their knock-out properties.

Normal values for myocardial deformation within the right heart measured by feature-tracking cardiovascular magnetic resonance imaging.

Science.gov (United States)

Liu, Boyang; Dardeer, Ahmed M; Moody, William E; Edwards, Nicola C; Hudsmith, Lucy E; Steeds, Richard P

2018-02-01

Reproducible and repeatable assessment of right heart function is vital for monitoring congenital and acquired heart disease. There is increasing evidence for the additional value of myocardial deformation (strain and strain rate) in determining prognosis. This study aims to determine the reproducibility of deformation analyses in the right heart using cardiovascular magnetic resonance feature tracking (FT-CMR); and to establish normal ranges within an adult population. A cohort of 100 healthy subjects containing 10 males and 10 females from each decade of life between the ages of 20 and 70 without known congenital or acquired cardiovascular disease, hypertension, diabetes, dyslipidaemia or renal, hepatic, haematologic and systemic inflammatory disorders underwent FT-CMR assessment of right ventricular (RV) and right atrial (RA) myocardial strain and strain rate. RV longitudinal strain (Ell) was -21.9±3.24% (FW+S Ell) and -24.2±3.59% (FW-Ell). Peak systolic strain rate (S') was -1.45±0.39s -1 (FW+S) and -1.54±0.41s -1 (FW). Early diastolic strain rate (E') was 1.04±0.26s -1 (FW+S) and 1.04±0.33s -1 (FW). Late diastolic strain rate (A') was 0.94±0.33s -1 (FW+S) and 1.08±0.33s -1 (FW). RA peak strain was -21.1±3.76%. The intra- and inter-observer ICC for RV Ell (FW+S) was 0.92 and 0.80 respectively, while for RA peak strain was 0.92 and 0.89 respectively. Normal values of RV & RA deformation for healthy individuals using FT-CMR are provided with good RV Ell and RA peak strain reproducibility. Strain rate suffered from sub-optimal reproducibility and may not be satisfactory for clinical use. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Combined heart-kidney transplantation after total artificial heart insertion.

Science.gov (United States)

Ruzza, A; Czer, L S C; Ihnken, K A; Sasevich, M; Trento, A; Ramzy, D; Esmailian, F; Moriguchi, J; Kobashigawa, J; Arabia, F

2015-01-01

We present the first single-center report of 2 consecutive cases of combined heart and kidney transplantation after insertion of a total artificial heart (TAH). Both patients had advanced heart failure and developed dialysis-dependent renal failure after implantation of the TAH. The 2 patients underwent successful heart and kidney transplantation, with restoration of normal heart and kidney function. On the basis of this limited experience, we consider TAH a safe and feasible option for bridging carefully selected patients with heart and kidney failure to combined heart and kidney transplantation. Recent FDA approval of the Freedom driver may allow outpatient management at substantial cost savings. The TAH, by virtue of its capability of providing pulsatile flow at 6 to 10 L/min, may be the mechanical circulatory support device most likely to recover patients with marginal renal function and advanced heart failure. Copyright © 2015 Elsevier Inc. All rights reserved.

Glucagon-like peptide-1 reduces contractile function and fails to boost glucose utilization in normal hearts in the presence of fatty acids.

Science.gov (United States)

Nguyen, T Dung; Shingu, Yasushige; Amorim, Paulo A; Schwarzer, Michael; Doenst, Torsten

2013-10-09

GLP-1 and exendin-4, which are used as insulin sensitizers or weight reducing drugs, were shown to improve glucose uptake in the heart. However, the direct effects of GLP-1 or exendin-4 on normal hearts in the presence of fatty acids, the main cardiac substrates, have never been investigated. We therefore assessed the effects of GLP-1 or exendin-4 on myocardial glucose uptake (GU), glucose oxidation (GO) and cardiac performance (CP) under conditions of fatty acid utilization. Rat hearts were perfused with only glucose (5 mM) or glucose (5 mM) plus oleate (0.4 mM) as substrates for 60 min. After 30 min, GLP-1 or exendin-4 (0.5 nM or 5 nM) was added. In the absence of oleate, GLP-1 increased both GU and GO. Exendin-4 increased GO but showed no effect on GU. Neither GLP-1 nor exendin-4 affected CP. However, when oleate was present, GLP-1 failed to stimulate glucose utilization and exendin-4 even decreased GU. Furthermore, now GLP-1 reduced CP. In contrast to prior reports, this negative inotropic effect could not be blocked by the protein kinase A inhibitor H-89. We then measured myocardial GO and CP in rats receiving a 4-week GLP-1 infusion. Interestingly, this chronic treatment resulted in a significant reduction in both GO and CP. Under the influence of oleate, GLP-1 reduces contractile function and fails to stimulate glucose utilization in normal hearts. Exendin-4 may acutely reduce cardiac glucose uptake but not contractility. We suggest advanced investigation of heart function and metabolism in patients treating with these peptides. © 2013.

Automatic heart rate normalization for accurate energy expenditure normalization : an analysis of activities of daily living and heart rate features

NARCIS (Netherlands)

Altini, M.; Penders, J.; Vullers, R.J.M.; Amft, O.D.

2014-01-01

Introduction: This article is part of the Focus Theme of Methods of Information in Medicine on "Pervasive Intelligent Technologies for Health". Background: Energy Expenditure (EE) estimation algorithms using Heart Rate (HR) or a combination of accelerometer and HR data suffer from large error due to

Nonlinear and Stochastic Dynamics in the Heart

Science.gov (United States)

Qu, Zhilin; Hu, Gang; Garfinkel, Alan; Weiss, James N.

2014-01-01

In a normal human life span, the heart beats about 2 to 3 billion times. Under diseased conditions, a heart may lose its normal rhythm and degenerate suddenly into much faster and irregular rhythms, called arrhythmias, which may lead to sudden death. The transition from a normal rhythm to an arrhythmia is a transition from regular electrical wave conduction to irregular or turbulent wave conduction in the heart, and thus this medical problem is also a problem of physics and mathematics. In the last century, clinical, experimental, and theoretical studies have shown that dynamical theories play fundamental roles in understanding the mechanisms of the genesis of the normal heart rhythm as well as lethal arrhythmias. In this article, we summarize in detail the nonlinear and stochastic dynamics occurring in the heart and their links to normal cardiac functions and arrhythmias, providing a holistic view through integrating dynamics from the molecular (microscopic) scale, to the organelle (mesoscopic) scale, to the cellular, tissue, and organ (macroscopic) scales. We discuss what existing problems and challenges are waiting to be solved and how multi-scale mathematical modeling and nonlinear dynamics may be helpful for solving these problems. PMID:25267872

Nonlinear and stochastic dynamics in the heart

Energy Technology Data Exchange (ETDEWEB)

Qu, Zhilin, E-mail: zqu@mednet.ucla.edu [Department of Medicine (Cardiology), David Geffen School of Medicine, University of California, Los Angeles, CA 90095 (United States); Hu, Gang [Department of Physics, Beijing Normal University, Beijing 100875 (China); Garfinkel, Alan [Department of Medicine (Cardiology), David Geffen School of Medicine, University of California, Los Angeles, CA 90095 (United States); Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095 (United States); Weiss, James N. [Department of Medicine (Cardiology), David Geffen School of Medicine, University of California, Los Angeles, CA 90095 (United States); Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 (United States)

2014-10-10

In a normal human life span, the heart beats about 2–3 billion times. Under diseased conditions, a heart may lose its normal rhythm and degenerate suddenly into much faster and irregular rhythms, called arrhythmias, which may lead to sudden death. The transition from a normal rhythm to an arrhythmia is a transition from regular electrical wave conduction to irregular or turbulent wave conduction in the heart, and thus this medical problem is also a problem of physics and mathematics. In the last century, clinical, experimental, and theoretical studies have shown that dynamical theories play fundamental roles in understanding the mechanisms of the genesis of the normal heart rhythm as well as lethal arrhythmias. In this article, we summarize in detail the nonlinear and stochastic dynamics occurring in the heart and their links to normal cardiac functions and arrhythmias, providing a holistic view through integrating dynamics from the molecular (microscopic) scale, to the organelle (mesoscopic) scale, to the cellular, tissue, and organ (macroscopic) scales. We discuss what existing problems and challenges are waiting to be solved and how multi-scale mathematical modeling and nonlinear dynamics may be helpful for solving these problems.

Nonlinear and stochastic dynamics in the heart

International Nuclear Information System (INIS)

Qu, Zhilin; Hu, Gang; Garfinkel, Alan; Weiss, James N.

2014-01-01

In a normal human life span, the heart beats about 2–3 billion times. Under diseased conditions, a heart may lose its normal rhythm and degenerate suddenly into much faster and irregular rhythms, called arrhythmias, which may lead to sudden death. The transition from a normal rhythm to an arrhythmia is a transition from regular electrical wave conduction to irregular or turbulent wave conduction in the heart, and thus this medical problem is also a problem of physics and mathematics. In the last century, clinical, experimental, and theoretical studies have shown that dynamical theories play fundamental roles in understanding the mechanisms of the genesis of the normal heart rhythm as well as lethal arrhythmias. In this article, we summarize in detail the nonlinear and stochastic dynamics occurring in the heart and their links to normal cardiac functions and arrhythmias, providing a holistic view through integrating dynamics from the molecular (microscopic) scale, to the organelle (mesoscopic) scale, to the cellular, tissue, and organ (macroscopic) scales. We discuss what existing problems and challenges are waiting to be solved and how multi-scale mathematical modeling and nonlinear dynamics may be helpful for solving these problems

Fokker-Planck simulations of knock-on electron runaway avalanche and bursts in tokamaks

International Nuclear Information System (INIS)

Chiu, S.C.; Rosenbluth, M.N.; Harvey, R.W.; Chan, V.S.

1998-01-01

The avalanche of runaway electrons in an ohmic tokamak plasma triggered by knock-on collisions of traces of energetic electrons with the bulk electrons is simulated by the bounce averaged Fokker-Planck code, CQL3D. It is shown that even when the electric field is small for the production of Dreicer runaways, the knock-on collisions can produce significant runaway electrons in a fraction of a second at typical reactor parameters. The energy spectrum of these knock-on runaways has a characteristic temperature. The growth rate and temperature of the runaway distribution are determined and compared with theory. In simulations of pellet injection into high temperature plasmas, it is shown that a burst of Dreicer runaways may also occur depending on the cooling rate due to the pellet injection. Implications of these phenomena on disruption control in reactor plasmas are discussed. (author)

Spark ignition engine performance and emissions in a high compression engine using biogas and methane mixtures without knock occurrence

Directory of Open Access Journals (Sweden)

Gómez Montoya Juan Pablo

2015-01-01

Full Text Available With the purpose to use biogas in an internal combustion engine with high compression ratio and in order to get a high output thermal efficiency, this investigation used a diesel engine with a maximum output power 8.5 kW, which was converted to spark ignition mode to use it with gaseous fuels. Three fuels were used: Simulated biogas, biogas enriched with 25% and 50% methane by volume. After conversion, the output power of the engine decreased by 17.64% when using only biogas, where 7 kW was the new maximum output power of the engine. The compression ratio was kept at 15.5:1, and knocking did not occur during engine operation. Output thermal efficiency operating the engine in SI mode with biogas enriched with 50% methane was almost the same compared with the engine running in diesel-biogas dual mode at full load and was greater at part loads. The dependence of the diesel pilot was eliminated when biogas was used in the engine converted in SI mode. The optimum condition of experiment for the engine without knocking was using biogas enriched with 50% methane, with 12 degrees of spark timing advance and equivalence ratio of 0.95, larger output powers and higher values of methane concentration lead the engine to knock operation. The presence of CO2 allows operating engines at high compression ratios with normal combustion conditions. Emissions of nitrogen oxides, carbon monoxide and unburnt methane all in g/kWh decreased when the biogas was enriched with 50% methane.

Study on the knock tendency and cyclical variations of a HCCI engine fueled with n-butanol/n-heptane blends

International Nuclear Information System (INIS)

Li, Gang; Zhang, Chunhua; Zhou, Jiawang

2017-01-01

Highlights: • The HCCI combustion was achieved on an engine fueled by n-butanol/n-heptane blends. • The knock tendency and cyclical variation of the HCCI combustion were studied. • The knock tendency can be weakened by increasing the blending ratio of n-butanol. • The knock tendency and cyclical variation are sensitive to the combustion phasing. • Cyclical variation always shows an opposite trend with the knock tendency. - Abstract: The homogeneous charge compression ignition (HCCI) combustion operation is conducted in the 2nd cylinder of a natural-aspirated four-stroke diesel engine. In the HCCI combustion mode, the n-butanol, n-heptane and their blends are injected into the intake port to form a lean homogeneous air-fuel mixture, which is consumed by the autoignition after compression. The objective of this study is to investigate the knock tendency and the cyclical variations of the HCCI engine. Experimental results show that the volume fraction of n-butanol affects the knock tendency greatly, which obviously decreases as the n-butanol volume fraction increases. The knocking combustion in the HCCI combustion is characterized by the high heat release rate (HRR). Both elevating the engine speed and raising the intake temperature contributes to an obvious increase in HRR and the knock tendency. But the HRR and knock tendency may slightly decrease when the engine speed reaches to 1400 rev/min and intake temperature reaches to 160 °C. Furthermore, the knock tendency can be weakened by increasing the excess air-fuel ratio. Cyclical variations of the HCCI engine are quantified by the coefficient of variation for the peak pressure (COV_P_m_a_x) and it exhibits an almost opposite trend to the knock tendency. The COV_P_m_a_x may considerably increase along with either increasing the blending ratio of n-butanol or increasing the excess air-fuel ratio. Moreover, it is reveled that the COV_P_m_a_x is sensitive to the relative position of peak HRR. The cyclical

Knock-on type exchange and the density dependence of an effective interaction

International Nuclear Information System (INIS)

Jeukenne, J.P.; Mahaux, C.

1981-01-01

We investigate the origin of the density-dependence of the strength of an effective interaction previously derived from a Brueckner-Hartree-Fock calculation of the optical-model potential in nuclear matter. From the analysis of a model based on the Hartree-Fock approximation and on a Yukawa interaction with a Majorana exchange component, we study to what extent this dependence derives from the momentum-dependence of the exchange contribution of the knock-on type. The model is also used to discuss zero-range pseudopotential methods for including this knock-on contribution. (orig.)

Contribution of the Arterial System and the Heart to Blood Pressure during Normal Aging - A Simulation Study.

Science.gov (United States)

Maksuti, Elira; Westerhof, Nico; Westerhof, Berend E; Broomé, Michael; Stergiopulos, Nikos

2016-01-01

During aging, systolic blood pressure continuously increases over time, whereas diastolic pressure first increases and then slightly decreases after middle age. These pressure changes are usually explained by changes of the arterial system alone (increase in arterial stiffness and vascular resistance). However, we hypothesise that the heart contributes to the age-related blood pressure progression as well. In the present study we quantified the blood pressure changes in normal aging by using a Windkessel model for the arterial system and the time-varying elastance model for the heart, and compared the simulation results with data from the Framingham Heart Study. Parameters representing arterial changes (resistance and stiffness) during aging were based on literature values, whereas parameters representing cardiac changes were computed through physiological rules (compensated hypertrophy and preservation of end-diastolic volume). When taking into account arterial changes only, the systolic and diastolic pressure did not agree well with the population data. Between 20 and 80 years, systolic pressure increased from 100 to 122 mmHg, and diastolic pressure decreased from 76 to 55 mmHg. When taking cardiac adaptations into account as well, systolic and diastolic pressure increased from 100 to 151 mmHg and decreased from 76 to 69 mmHg, respectively. Our results show that not only the arterial system, but also the heart, contributes to the changes in blood pressure during aging. The changes in arterial properties initiate a systolic pressure increase, which in turn initiates a cardiac remodelling process that further augments systolic pressure and mitigates the decrease in diastolic pressure.

AcvR1-mediated BMP signaling in second heart field is required for arterial pole development: implications for myocardial differentiation and regional identity.

Science.gov (United States)

Thomas, Penny S; Rajderkar, Sudha; Lane, Jamie; Mishina, Yuji; Kaartinen, Vesa

2014-06-15

BMP signaling plays an essential role in second heart field-derived heart and arterial trunk development, including myocardial differentiation, right ventricular growth, and interventricular, outflow tract and aortico-pulmonary septation. It is mediated by a number of different BMP ligands, and receptors, many of which are present simultaneously. The mechanisms by which they regulate morphogenetic events and degree of redundancy amongst them have still to be elucidated. We therefore assessed the role of BMP Type I receptor AcvR1 in anterior second heart field-derived cell development, and compared it with that of BmpR1a. By removing Acvr1 using the driver Mef2c[AHF]-Cre, we show that AcvR1 plays an essential role in arterial pole morphogenesis, identifying defects in outflow tract wall and cushion morphology that preceded a spectrum of septation defects from double outlet right ventricle to common arterial trunk in mutants. Its absence caused dysregulation in gene expression important for myocardial differentiation (Isl1, Fgf8) and regional identity (Tbx2, Tbx3, Tbx20, Tgfb2). Although these defects resemble to some degree those in the equivalent Bmpr1a mutant, a novel gene knock-in model in which Bmpr1a was expressed in the Acvr1 locus only partially restored septation in Acvr1 mutants. These data show that both BmpR1a and AcvR1 are needed for normal heart development, in which they play some non-redundant roles, and refine our understanding of the genetic and morphogenetic processes underlying Bmp-mediated heart development important in human congenital heart disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Normal position and malposition of the heart

International Nuclear Information System (INIS)

Andresen, J.H.; Eggert Hansen, T.

1980-01-01

The main types of heart positions and the malpositions are described as demonstrated on plain films of the thorax. Special attention is drawn to the situs ambiguous with the poly- or asplenia which may be recognized from hypoarterial or epiarterial position of the main bronchi and their equal lengths and courses. This diagnosis is important because of the frequent accompanying congenital cardiac malformations and in respect to the planning of angiocardiography. (orig.) [de

31P MR spectroscopic measurement of intracellular pH in normal human hearts

International Nuclear Information System (INIS)

Kwon, Jae Hyun; Lee, Hui Joong; Jang, Yong Min

2002-01-01

To assess the usefulness of intracellular pH (pHi), calculated by determining the shift of a high-energy metabolite such as inorganic phosphate (Pi) of γ-ATP after performing MRS with ECG-gated two-dimensional 31 P CSI (chemical shift imaging), as a parameter for the overall state of the intracellular milieu. Proto decoupled 31 P CSI was performed on a 1.5-T scanner using a 1 H 31 P dual-tuned surface coil. Cardiac MRS data were obtained from eight normal volunteers aged 24-32 years with no history of heart disease. From the spectra obtained from several regions of the heart, peack position and peak area were estimated. The metabolic ratios of α-, β-, γ-ATP, PCr, Pi, phosphodiester and diphosphoglycerate were calculated, and pHi was estimated from the chemical shift of Pi and γ-ATP resonance. We then compared the data for the anterior myocardium with those previously published. The major phosphorous metabolites identified in these human hearts were as follows: PCr, at -0.1 to +0.1 ppm; three phosphate peaks from ATP, with a chemical shift centered at about -2.7 ppm (γ-ATP), -7.8 ppm (α-ATP), and -16.3 ppm (β-ATP); and phosphodiester (PDE) at 2-3 ppm, inorganic phosphate (Pi) at 4.5-5.4 ppm, and diphosphoglycerate (DPG) at 5.4-6.3 ppm. The PCr/β-ATP ratio was 2.20±0.17 and the PDE/β-ATP ratio, 1.04±0.09 pHi readings were 7.31±0.23 (calculated by the shift of Pi) and 6.81±0.20 (calculated by the shift of γ-ATP). Pi/PCR was 0.539, a ratio higher than that mentioned in previously published reports. The measurement of intracellular metabolism was affected by various kinds of factors. We believe, however, that pHi readings indicate the overall state of the cardiac intracellular milieu. An unexpected pHi readings, seen at MRS, may reflect errors in the MR procedure itself and, or in the analytical method

Knock Prediction Using a Simple Model for Ignition Delay

KAUST Repository

Kalghatgi, Gautam; Morganti, Kai; Algunaibet, Ibrahim; Sarathy, Mani; Dibble, Robert W.

2016-01-01

An earlier paper has shown the ability to predict the phasing of knock onset in a gasoline PFI engine using a simple ignition delay equation for an appropriate surrogate fuel made up of toluene and PRF (TPRF). The applicability of this approach

Atrial and Ventricular Electrocardiographic Dromotropic Disturbances in Down Syndrome Patients with Structurally Normal Heart: A Cross-Sectional Study

Directory of Open Access Journals (Sweden)

Yazdan Ghandi

2018-03-01

Full Text Available Background: We designed a cross-sectional study to determine electrocardiographic disorders in Down syndrome patients with congenitally normal hearts in a bid to predict fatal cardiac arrhythmia in the future. Materials and Methods: We investigated 60 children with DS without congenital abnormal hearts. Sixty healthy juveniles were also included in the study as a control group. Physical examination, electrocardiography, and echocardiography were performed in all subjects. Corrected QT interval (QTc was measured according to Bazett’s formula. Results: Patients with DS consisted of 32 males (53.33%, and 28 females (46.66%, aged 6–13 (9.21 ± 6.24 years old. Healthy subjects comprised 31 males (51.66%, and 29 females (48.33% with a mean age of 9.15 ± 5.01. The two groups were significantly different in terms of heart rate (P=0.006, maximum P-wave duration (P=0.001, and P-wave dispersion (PWd, P=0.0001. There was no statistically significant difference regarding minimum P-wave duration (P=0.176. The patients with DS had a greater maximum QTc interval, QT dispersion, and corrected QT interval dispersion (QTc-d than the healthy control subjects (P=0.001. However, there was no difference in maximum QT interval and minimum QTc interval between the two groups (P=0.67 and P=0.553, respectively. A positive correlation was found between age, heart rate, and all electrocardiographic variables. Conclusion: All DS patients, even in the absence of concomitant congenital heart disease should be followed up carefully by electrocardiography, looking for increased PWd and QTc-d to detect predisposed cases to arrhythmia.

Computer simulation of the spatial distribution of optical radiation arising from knocked-out excited particles

International Nuclear Information System (INIS)

Gokov, S.P.; Gritsyna, V.V.; Koval', A.G.; Kovtunenko, Yu.I.; Shevchenko, D.I.

2004-01-01

The new approach for the explanation of the spatial distribution of the optical radiation arising from knocked-out excited particles is given. Calculated and experimental data for Al (λ=396.1 nm) and Mg (λ=383.8 nm) knocked-out by Ar + (20 keV) beam from MgAl 2 O 4 surface are compared [ru

Signal Transducer and Activator of Transcription 1 (STAT1) Knock-down Induces Apoptosis in Malignant Pleural Mesothelioma.

Science.gov (United States)

Arzt, Lisa; Halbwedl, Iris; Gogg-Kamerer, Margit; Popper, Helmut H

2017-07-01

Malignant pleural mesothelioma (MPM) is the most common primary tumor of the pleura. Its incidence is still increasing in Europe and the prognosis remains poor. We investigated the oncogenic function of signal transducer and activator of transcription 1 (STAT1) in MPM in more detail. A miRNA profiling was performed on 52 MPM tissue samples. Upregulated miRNAs (targeting SOCS1/3) were knocked-down using miRNA inhibitors. mRNA expression levels of STAT1/3, SOCS1/3 were detected in MPM cell lines. STAT1 has been knocked-down using siRNA and qPCR was used to detect mRNA expression levels of all JAK/STAT family members and genes that regulate them. An immunohistochemical staining was performed to detect the expression of caspases. STAT1 was upregulated and STAT3 was downregulated, SOCS1/3 protein was not detected but it was possible to detect SOCS1/3 mRNA in MPM cell lines. The upregulated miRNAs were successfully knocked-down, however the expected effect on SOCS1 expression was not detected. STAT1 knock-down had different effects on STAT3/5 expression. Caspase 3a and 8 expression was found to be increased after STAT1 knock-down. The physiologic regulation of STAT1 via SOCS1 is completely lost in MPM and it does not seem that the miRNAs identified by now, do inhibit the expression of SOCS1. MPM cell lines compensate STAT1 knock-down by increasing the expression of STAT3 or STAT5a, two genes which are generally considered to be oncogenes. And much more important, STAT1 knock-down induces apoptosis in MPM cell lines and STAT1 might therefore be a target for therapeutic intervention.

Analysis of Knock Phenomenon Induced in a Constant Volume Chamber by Local Gas Temperature Measurement and Visualization

Science.gov (United States)

Moriyoshi, Yasuo; Kobayashi, Shigemi; Enomoto, Yoshiteru

Knock phenomenon in SI engines is regarded as an auto-ignition of unburned end-gas, and it has been widely examined by using rapid compression machines (RCM), shock-tubes or test engines. Recent researches point out the importance of the low temperature chemical reaction and the negative temperature coefficient (NTC). To investigate the effects, analyses of instantaneous local gas temperature, flow visualization and gaseous pressure were conducted in this study. As measurements using real engines are too difficult to analyze, the authors aimed to make measurements using a constant volume vessel under knock conditions where propagating flame exists during the induction time of auto-ignition. Adopting the two-wire thermocouple method enabled us to measure the instantaneous local gas temperature until the moment when the flame front passes by. High-speed images inside the unburned region were also recorded simultaneously using an endoscope. As a result, it was found that when knock occurs, the auto-ignition initiation time seems slightly early compared to the results without knock. This causes a higher volume ratio of unburned mixture and existence of many hot spots and stochastically leads to an initiation of knock.

Single proton knock-out from 24F

International Nuclear Information System (INIS)

Thoennessen, M.; Baumann, T.; Brown, B.A.; Enders, J.; Frank, N.H.; Hansen, P.G.; Heckman, P.; Luther, B.A.; Seitz, J.P.; Stolz, A.; Tryggestad, E.

2004-01-01

The measurement of the single proton knock-out reaction from 24 F on a 12 C target at 46.7 MeV/nucleon yielded a 23 O ground state population of (6.6+/-1.0) mb. The data were compared to calculations based on the many-body shell model and the eikonal theory. The results are consistent with a [0d5/26]-bar 1s1/2 configuration of 23 O

Characterization of a knock-in mouse model of the homozygous p.V37I variant in Gjb2.

Science.gov (United States)

Chen, Ying; Hu, Lingxiang; Wang, Xueling; Sun, Changling; Lin, Xin; Li, Lei; Mei, Ling; Huang, Zhiwu; Yang, Tao; Wu, Hao

2016-09-13

The homozygous p.V37I variant in GJB2 is prevalent in East and Southeast Asians and may lead to mild-to-moderate hearing loss with reduced penetrance. To investigate the pathogenic mechanism underlying this variant, we generated a knock-in mouse model of homozygous p.V37I by an embryonic stem cell gene targeting method. Auditory brainstem response test showed that the knock-in mice developed progressive, mild-to-moderate hearing loss over the first 4-9 months. Overall no significant developmental and morphological abnormality was observed in the knock-in mouse cochlea, while confocal immunostaining and electron microscopic scanning revealed minor loss of the outer hair cells. Gene expression microarray analysis identified 105 up-regulated and 43 down-regulated genes in P5 knock-in mouse cochleae (P knock-in mouse modeled the hearing phenotype of the human patients and can serve as a useful animal model for further studies. The differentially expressed genes identified in this study may shed new insights into the understanding of the pathogenic mechanism and the phenotypic modification of homozygous p.V37I.

Genetic Contributors to Intergenerational CAG Repeat Instability in Huntington's Disease Knock-In Mice.

Science.gov (United States)

Neto, João Luís; Lee, Jong-Min; Afridi, Ali; Gillis, Tammy; Guide, Jolene R; Dempsey, Stephani; Lager, Brenda; Alonso, Isabel; Wheeler, Vanessa C; Pinto, Ricardo Mouro

2017-02-01

Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in exon 1 of the HTT gene. Longer repeat sizes are associated with increased disease penetrance and earlier ages of onset. Intergenerationally unstable transmissions are common in HD families, partly underlying the genetic anticipation seen in this disorder. HD CAG knock-in mouse models also exhibit a propensity for intergenerational repeat size changes. In this work, we examine intergenerational instability of the CAG repeat in over 20,000 transmissions in the largest HD knock-in mouse model breeding datasets reported to date. We confirmed previous observations that parental sex drives the relative ratio of expansions and contractions. The large datasets further allowed us to distinguish effects of paternal CAG repeat length on the magnitude and frequency of expansions and contractions, as well as the identification of large repeat size jumps in the knock-in models. Distinct degrees of intergenerational instability were observed between knock-in mice of six background strains, indicating the occurrence of trans-acting genetic modifiers. We also found that lines harboring a neomycin resistance cassette upstream of Htt showed reduced expansion frequency, indicative of a contributing role for sequences in cis, with the expanded repeat as modifiers of intergenerational instability. These results provide a basis for further understanding of the mechanisms underlying intergenerational repeat instability. Copyright © 2017 by the Genetics Society of America.

Knock-out of a mitochondrial sirtuin protects neurons from degeneration in Caenorhabditis elegans.

Science.gov (United States)

Sangaletti, Rachele; D'Amico, Massimo; Grant, Jeff; Della-Morte, David; Bianchi, Laura

2017-08-01

Sirtuins are NAD⁺-dependent deacetylases, lipoamidases, and ADP-ribosyltransferases that link cellular metabolism to multiple intracellular pathways that influence processes as diverse as cell survival, longevity, and cancer growth. Sirtuins influence the extent of neuronal death in stroke. However, different sirtuins appear to have opposite roles in neuronal protection. In Caenorhabditis elegans, we found that knock-out of mitochondrial sirtuin sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis. Furthermore, the protective effect of sir-2.3 knock-out is enhanced by block of glycolysis and eliminated by a null mutation in daf-16/FOXO transcription factor, supporting the involvement of the insulin/IGF pathway. However, data in Caenorhabditis elegans cell culture suggest that the effects of sir-2.3 knock-out act downstream of the DAF-2/IGF-1 receptor. Analysis of ROS in sir-2.3 knock-out reveals that ROS become elevated in this mutant under ischemic conditions in dietary deprivation (DD), but to a lesser extent than in wild type, suggesting more robust activation of a ROS scavenging system in this mutant in the absence of food. This work suggests a deleterious role of SIRT4 during ischemic processes in mammals that must be further investigated and reveals a novel pathway that can be targeted for the design of therapies aimed at protecting neurons from death in ischemic conditions.

Visibility graph analysis of heart rate time series and bio-marker of congestive heart failure

Science.gov (United States)

Bhaduri, Anirban; Bhaduri, Susmita; Ghosh, Dipak

2017-09-01

Study of RR interval time series for Congestive Heart Failure had been an area of study with different methods including non-linear methods. In this article the cardiac dynamics of heart beat are explored in the light of complex network analysis, viz. visibility graph method. Heart beat (RR Interval) time series data taken from Physionet database [46, 47] belonging to two groups of subjects, diseased (congestive heart failure) (29 in number) and normal (54 in number) are analyzed with the technique. The overall results show that a quantitative parameter can significantly differentiate between the diseased subjects and the normal subjects as well as different stages of the disease. Further, the data when split into periods of around 1 hour each and analyzed separately, also shows the same consistent differences. This quantitative parameter obtained using the visibility graph analysis thereby can be used as a potential bio-marker as well as a subsequent alarm generation mechanism for predicting the onset of Congestive Heart Failure.

Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart

NARCIS (Netherlands)

Schultz, D; Mikala, G; Yatani, A; Engle, D B; Iles, D E; Segers, B; Sinke, R J; Weghuis, D O; Klöckner, U; Wakamori, M

1993-01-01

A unique structural variant of the cardiac L-type voltage-dependent calcium channel alpha 1 subunit cDNA was isolated from libraries derived from normal human heart mRNA. The deduced amino acid sequence shows significant homology to other calcium channel alpha 1 subunits. However, differences from

Heart rate variability in healthy population

International Nuclear Information System (INIS)

Alamgir, M.; Hussain, M.M.

2010-01-01

Background: Heart rate variability has been considered as an indicator of autonomic status. Little work has been done on heart rate variability in normal healthy volunteers. We aimed at evolving the reference values of heart rate variability in our healthy population. Methods: Twenty-four hour holter monitoring of 37 healthy individuals was done using Holter ECG recorder 'Life card CF' from 'Reynolds Medical'. Heart rate variability in both time and frequency domains was analysed with 'Reynolds Medical Pathfinder Digital/700'. Results: The heart rate variability in normal healthy volunteers of our population was found in time domain using standard deviation of R-R intervals (SDNN), standard deviation of average NN intervals (SDANN), and Square root of the mean squared differences of successive NN intervals (RMSSD). Variation in heart rate variability indices was observed between local and foreign volunteers and RMSSD was found significantly increased (p<0.05) in local population. Conclusions: The values of heart rate variability (RMSSD) in healthy Pakistani volunteers were found increased compared to the foreign data reflecting parasympathetic dominance in our population. (author)

Temperature dependence of knocking-out cross sections of a bound atom from the lattice site

International Nuclear Information System (INIS)

Zhdanov, S.K.; Pletnev, V.V.

1981-01-01

The total cross section of atom knocking-out from the lattice site is calculated with the atom binding in the lattice site taken into account. The intermediate case of atom being preads over the bottom of a spherical potential well is considered (the case of intermediate temperatures). Thus the target temperature parameter enters the equation for the total cross section of atom knocking-out

Knock-limited performance of several internal coolants

Science.gov (United States)

Bellman, Donald R; Evvard, John C

1945-01-01

The effect of internal cooling on the knock-limited performance of an-f-28 fuel was investigated in a CFR engine, and the following internal coolants were used: (1) water, (2), methyl alcohol-water mixture, (3) ammonia-methyl alcohol-water mixture, (4) monomethylamine-water mixture, (5) dimethylamine-water mixture, and (6) trimethylamine-water mixture. Tests were run at inlet-air temperatures of 150 degrees and 250 degrees F. to indicate the temperature sensitivity of the internal-coolant solutions.

William Knocke receives 2008 Virginia Outstanding Civil Engineer Award

OpenAIRE

Daniilidi, Christina

2008-01-01

William R. Knocke, W.C. English Professor and head of the Charles E. Via, Jr. Department of Civil and Environmental Engineering at Virginia Tech, was awarded the 2008 Virginia Outstanding Civil Engineer Award at the Virginia Section of the American Society of Civil Engineers' (ASCE) banquet, held recently in Williamsburg, Va.

A model of knock-out of oxygen by charged particle irradiation of Bi-2212

International Nuclear Information System (INIS)

Bandyopadhyay, S.K.; Sen, Pintu; Barat, P.; Mukherjee, P.; Das, S.K.; Ghosh, B.

1996-01-01

A model of knock-out of oxygen by charged particle (α and proton) irradiation of Bi 2 Sr 2 CaCu 2 O 8+x (Bi-2212) is proposed on the basis of Monte Carlo TRIM calculations. In Bi-2212, the loosely bound excess oxygen is vulnerable to be displaced by particle irradiation. Binding energy and hence, displacement energy of this loosely bound excess oxygen is less compared to that of stoichiometric lattice bound oxygen and other atoms. The displaced or knocked out oxygen goes to pores or intergranular region and generates large pressure inside the sample. Because of porosity of the material, this displaced oxygen diffuses out and there is a net reduction of oxygen content of the sample. The irradiation induced oxygen knock-out is dominant in the bulk where nonionizing energy loss is maximum. (author). 29 refs., 1 fig., 3 tabs

Radiochemicals used to scan the heart

International Nuclear Information System (INIS)

Anon.

1975-01-01

Techniques for heart scanning using 201 Tl and /sup 99m/Tc pyrophosphate are discussed. Thallium-201, produced artificially in a cyclotron, concentrates in normal heart muscle but not in abnormal tissue. Technetium-99m is deposited in mitochondria of heart cells that are irreversibly damaged. The combined use of 201 Tl and /sup 99m/Tc makes it possible to identify regions of recent heart damage as well as older heart damage. Advantages of using 129 Cs for heart scanning are also discussed

Efficient Knock-in of a Point Mutation in Porcine Fibroblasts Using the CRISPR/Cas9-GMNN Fusion Gene.

Science.gov (United States)

Gerlach, Max; Kraft, Theresia; Brenner, Bernhard; Petersen, Björn; Niemann, Heiner; Montag, Judith

2018-06-13

During CRISPR/Cas9 mediated genome editing, site-specific double strand breaks are introduced and repaired either unspecific by non-homologous end joining (NHEJ) or sequence dependent by homology directed repair (HDR). Whereas NHEJ-based generation of gene knock-out is widely performed, the HDR-based knock-in of specific mutations remains a bottleneck. Especially in primary cell lines that are essential for the generation of cell culture and animal models of inherited human diseases, knock-in efficacy is insufficient and needs significant improvement. Here, we tested two different approaches to increase the knock-in frequency of a specific point mutation into the MYH7 -gene in porcine fetal fibroblasts. We added a small molecule inhibitor of NHEJ, SCR7 (5,6-bis((E)-benzylideneamino)-2-mercaptopyrimidin-4-ol), during genome editing and screened cell cultures for the point mutation. However, this approach did not yield increased knock-in rates. In an alternative approach, we fused humanized Cas9 (hCas9) to the N-terminal peptide of the Geminin gene ( GMNN ). The fusion protein is degraded in NHEJ-dominated cell cycle phases, which should increase HDR-rates. Using hCas9- GMNN and point mutation-specific real time PCR screening, we found a two-fold increase in genome edited cell cultures. This increase of HDR by hCas9- GMNN provides a promising way to enrich specific knock-in in porcine fibroblast cultures for somatic cloning approaches.

Efficient generation of knock-in transgenic zebrafish carrying reporter/driver genes by CRISPR/Cas9-mediated genome engineering.

Science.gov (United States)

Kimura, Yukiko; Hisano, Yu; Kawahara, Atsuo; Higashijima, Shin-ichi

2014-10-08

The type II bacterial CRISPR/Cas9 system is rapidly becoming popular for genome-engineering due to its simplicity, flexibility, and high efficiency. Recently, targeted knock-in of a long DNA fragment via homology-independent DNA repair has been achieved in zebrafish using CRISPR/Cas9 system. This raised the possibility that knock-in transgenic zebrafish could be efficiently generated using CRISPR/Cas9. However, how widely this method can be applied for the targeting integration of foreign genes into endogenous genomic loci is unclear. Here, we report efficient generation of knock-in transgenic zebrafish that have cell-type specific Gal4 or reporter gene expression. A donor plasmid containing a heat-shock promoter was co-injected with a short guide RNA (sgRNA) targeted for genome digestion, a sgRNA targeted for donor plasmid digestion, and Cas9 mRNA. We have succeeded in establishing stable knock-in transgenic fish with several different constructs for 4 genetic loci at a frequency being exceeding 25%. Due to its simplicity, design flexibility, and high efficiency, we propose that CRISPR/Cas9-mediated knock-in will become a standard method for the generation transgenic zebrafish.

{sup 31}P MR spectroscopic measurement of intracellular pH in normal human hearts

Energy Technology Data Exchange (ETDEWEB)

Kwon, Jae Hyun; Lee, Hui Joong; Jang, Yong Min [Kyungpook National Univ., Taegu (Korea, Republic of)] [and others

2002-05-01

To assess the usefulness of intracellular pH (pHi), calculated by determining the shift of a high-energy metabolite such as inorganic phosphate (Pi) of {gamma}-ATP after performing MRS with ECG-gated two-dimensional {sup 31}P CSI (chemical shift imaging), as a parameter for the overall state of the intracellular milieu. Proto decoupled {sup 31}P CSI was performed on a 1.5-T scanner using a {sup 1}H{sup 31}P dual-tuned surface coil. Cardiac MRS data were obtained from eight normal volunteers aged 24-32 years with no history of heart disease. From the spectra obtained from several regions of the heart, peack position and peak area were estimated. The metabolic ratios of {alpha}-, {beta}-, {gamma}-ATP, PCr, Pi, phosphodiester and diphosphoglycerate were calculated, and pHi was estimated from the chemical shift of Pi and {gamma}-ATP resonance. We then compared the data for the anterior myocardium with those previously published. The major phosphorous metabolites identified in these human hearts were as follows: PCr, at -0.1 to +0.1 ppm; three phosphate peaks from ATP, with a chemical shift centered at about -2.7 ppm ({gamma}-ATP), -7.8 ppm ({alpha}-ATP), and -16.3 ppm ({beta}-ATP); and phosphodiester (PDE) at 2-3 ppm, inorganic phosphate (Pi) at 4.5-5.4 ppm, and diphosphoglycerate (DPG) at 5.4-6.3 ppm. The PCr/{beta}-ATP ratio was 2.20{+-}0.17 and the PDE/{beta}-ATP ratio, 1.04{+-}0.09 pHi readings were 7.31{+-}0.23 (calculated by the shift of Pi) and 6.81{+-}0.20 (calculated by the shift of {gamma}-ATP). Pi/PCR was 0.539, a ratio higher than that mentioned in previously published reports. The measurement of intracellular metabolism was affected by various kinds of factors. We believe, however, that pHi readings indicate the overall state of the cardiac intracellular milieu. An unexpected pHi readings, seen at MRS, may reflect errors in the MR procedure itself and, or in the analytical method.

Effect of Lactobacillus delbrueckii on cholesterol metabolism in germ-free mice and on atherogenesis in apolipoprotein E knock-out mice

Directory of Open Access Journals (Sweden)

Portugal L.R.

2006-01-01

Full Text Available Elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. Several studies have reported a decrease in serum cholesterol during the consumption of large doses of fermented dairy products or lactobacillus strains. The proposed mechanism for this effect is the removal or assimilation of intestinal cholesterol by the bacteria, reducing cholesterol absorption. Although this effect was demonstrated in vitro, its relevance in vivo is still controversial. Furthermore, few studies have investigated the role of lactobacilli in atherogenesis. The aim of the present study was to determine the effect of Lactobacillus delbrueckii on cholesterol metabolism in germ-free mice and the possible hypocholesterolemic and antiatherogenic action of these bacteria using atherosclerosis-prone apolipoprotein E (apo E knock-out (KO mice. For this purpose, Swiss/NIH germ-free mice were monoassociated with L. delbrueckii and fed a hypercholesterolemic diet for four weeks. In addition, apo E KO mice were fed a normal chow diet and treated with L. delbrueckii for 6 weeks. There was a reduction in cholesterol excretion in germ-free mice, which was not associated with changes in blood or liver cholesterol concentration. In apo E KO mice, no effect of L. delbrueckii was detected in blood, liver or fecal cholesterol. The atherosclerotic lesion in the aorta was also similar in mice receiving or not these bacteria. In conclusion, these results suggest that, although L. delbrueckii treatment was able to reduce cholesterol excretion in germ-free mice, no hypocholesterolemic or antiatherogenic effect was observed in apo E KO mice.

Heart failure: when form fails to follow function.

Science.gov (United States)

Katz, Arnold M; Rolett, Ellis L

2016-02-01

Cardiac performance is normally determined by architectural, cellular, and molecular structures that determine the heart's form, and by physiological and biochemical mechanisms that regulate the function of these structures. Impaired adaptation of form to function in failing hearts contributes to two syndromes initially called systolic heart failure (SHF) and diastolic heart failure (DHF). In SHF, characterized by high end-diastolic volume (EDV), the left ventricle (LV) cannot eject a normal stroke volume (SV); in DHF, with normal or low EDV, the LV cannot accept a normal venous return. These syndromes are now generally defined in terms of ejection fraction (EF): SHF became 'heart failure with reduced ejection fraction' (HFrEF) while DHF became 'heart failure with normal or preserved ejection fraction' (HFnEF or HFpEF). However, EF is a chimeric index because it is the ratio between SV--which measures function, and EDV--which measures form. In SHF the LV dilates when sarcomere addition in series increases cardiac myocyte length, whereas sarcomere addition in parallel can cause concentric hypertrophy in DHF by increasing myocyte thickness. Although dilatation in SHF allows the LV to accept a greater venous return, it increases the energy cost of ejection and initiates a vicious cycle that contributes to progressive dilatation. In contrast, concentric hypertrophy in DHF facilitates ejection but impairs filling and can cause heart muscle to deteriorate. Differences in the molecular signals that initiate dilatation and concentric hypertrophy can explain why many drugs that improve prognosis in SHF have little if any benefit in DHF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Potentials of cooled EGR and water injection for knock resistance and fuel consumption improvements of gasoline engines

International Nuclear Information System (INIS)

Bozza, Fabio; De Bellis, Vincenzo; Teodosio, Luigi

2016-01-01

Highlights: • 1D simulation of a turbocharged VVA engine under knock limited operation. • Description of turbulence, combustion and knock by phenomenological models. • Comparison of EGR and ported water injection at high load for knock mitigation and fuel economy. • Virtual calibration of engine control parameters by a 1D model. - Abstract: It is well known that the downsizing philosophy allows the improvement of the brake specific fuel consumption (BSFC) at part load operation for spark ignition (SI) engines. On the other hand, the BSFC is penalized at high load because of the knock occurrence and of further limitations on the turbine inlet temperature (TIT). Knock control forces the adoption of a late combustion phasing, causing a deterioration of the thermodynamic efficiency, while the TIT control requires the enrichment of the air-to-fuel ratio (A/F), with additional BSFC drawbacks. In this work, two promising techniques are investigated by a 1D approach with the aim of improving the fuel economy of a turbocharged SI engine at full load knock-limited operation. The first technique is the recirculation of low-pressure cooled exhaust gas (EGR), while the second is the injection of liquid water at the intake ports. Proper “in-house developed” sub-models are used to describe the turbulence, combustion and knock phenomena. The effects of the above techniques are studied in six operating points at full load and different speeds for various A/F levels and inert content, by varying the EGR rate and water-to-fuel ratio. The presented results highlight that both the solutions involve significant BSFC improvements, especially in the operating conditions at medium engine speeds. In fact, the introduction of inert gas in the cylinder contributes to reduce the knock tendency, resulting in the possibility to advance the combustion phasing and reduce, or even avoid, the mixture over-fuelling. The heat subtracted by the water evaporation enhances the above effects

Normal and abnormal electrical activation of the heart. Imaging patterns obtained by phase analysis of equilibrium cardiac studies

International Nuclear Information System (INIS)

Pavel, D.; Byrom, E.; Swiryn, S.; Meyer-Pavel, C.; Rosen, K.

1981-01-01

By using a temporal Fourier analysis of gated equilibrium cardiac studies, phase images were obtained. These functional images were analysed qualitatively and quantitatively to determine if specific patterns can be found for normal versus abnormal electrical activation of the heart. The study included eight subjects with normal cardiac function and 24 patients with abnormal electrical activation: eight with left bundle branch block (LBBB), two with right bundle branch block (RBBB), six with Wolff-Parkinson-White syndrome (WPW), one with junctional rhythm, one with spontaneous sustained ventricular tachycardia (VT) (all with normal wall motion), two with chronic transvenous pacemakers, and four with induced sustained VT (all with regional wall motion abnormalities). The results show that the two ventricals have the same mean phase (within +-9 0 ) in normals, but significantly different mean phases in all patients with bundle branch blocks. Of the six WPW patients, three had a distinctive abnormal pattern. The patient with junctional rhythm, those with transvenous pacemakers, and those with VT all had abnormal patterns on the phase image. The phase image is capable of showing differences between patients with electrical activation and a variety of electrical abnormalities. Within the latter category distinct patterns can be associated with each type of abnormality. (author)

Pion-induced knock-out reactions

International Nuclear Information System (INIS)

Jain, B.K.; Phatak, S.C.

1977-01-01

A strong absorption model for pion-induced Knock-out reactions is proposed. The distortion of the in-coming and out-going pions has been included by (1) computing pion wave number in nuclear medium (dispersive effect) and (2) excluding the central region of the nucleus where the real pion-absorption is dominant (absorption effect). In order to study the dependence of the (π + π + p) reaction on the off-shell pion-nucleon t-matrix, different off-shell extrapolations are used. The magnitude of the cross-sections seems to be sensitive to the type of off-shell extrapolation; their shapes, however, are similar. The theoretical results are compared with experimental data. The agreement between the theoretical results for separable off-shell extrapolation and the data is good. (author)

Identification of rat Rosa26 locus enables generation of knock-in rat lines ubiquitously expressing tdTomato.

Science.gov (United States)

Kobayashi, Toshihiro; Kato-Itoh, Megumi; Yamaguchi, Tomoyuki; Tamura, Chihiro; Sanbo, Makoto; Hirabayashi, Masumi; Nakauchi, Hiromitsu

2012-11-01

Recent discovery of a method for derivation and culture of germline-competent rat pluripotent stem cells (PSCs) enables generation of transgenic rats or knock-out rats via genetic modification of such PSCs. This opens the way to use rats, as is routine in mice, for analyses of gene functions or physiological features. In mouse or human, one widely used technique to express a gene of interest stably and ubiquitously is to insert that gene into the Rosa26 locus via gene targeting of PSCs. Rosa26 knock-in mice conditionally expressing a reporter or a toxin gene have contributed to tracing or ablation of specific cell lineages. We successfully identified a rat orthologue of the mouse Rosa26 locus. Insertion of tdTomato, a variant of red fluorescent protein, into the Rosa26 locus of PSCs of various rat strains allows ubiquitous expression of tdTomato. Through germline transmission of one Rosa26-tdTomato knock-in embryonic stem cell line, we also obtained tdTomato knock-in rats. These expressed tdTomato ubiquitously throughout their bodies, which indicates that the rat Rosa26 locus conserves functions of its orthologues in mouse and human. The new tools described here (targeting vectors, knock-in PSCs, and rats) should be useful for a variety of research using rats.

Predicting the names of the best teams after the knock-out phase of a cricket series.

Science.gov (United States)

Lemmer, Hermanus Hofmeyr

2014-01-01

Cricket players' performances can best be judged after a large number of matches had been played. For test or one-day international (ODI) players, career data are normally used to calculate performance measures. These are normally good indicators of future performances, although various factors influence the performance of a player in a specific match. It is often necessary to judge players' performances based on a small number of scores, e.g. to identify the best players after a short series of matches. The challenge then is to use the best available criteria in order to assess performances as accurately and fairly as possible. In the present study the results of the knock-out phase of an International Cricket Council (ICC) World Cup ODI Series are used to predict the names of the best teams by means of a suitably formulated logistic regression model. Despite using very sparse data, the methods used are reasonably successful. It is also shown that if the same technique is applied to career ratings, very good results are obtained.

A hard-knock life: the foraging ecology of Cape cormorants amidst ...

African Journals Online (AJOL)

A hard-knock life: the foraging ecology of Cape cormorants amidst shifting prey resources and industrial fishing pressure. MH Hamann, D Grémillet, PG Ryan, F Bonadonna, CD van der Lingen, L Pichegru ...

Culture time of vitrified/warmed zygotes before microinjection affects the production efficiency of CRISPR-Cas9-mediated knock-in mice.

Science.gov (United States)

Nakagawa, Yoshiko; Sakuma, Tetsushi; Nishimichi, Norihisa; Yokosaki, Yasuyuki; Takeo, Toru; Nakagata, Naomi; Yamamoto, Takashi

2017-05-15

Robust reproductive engineering techniques are required for the efficient and rapid production of genetically modified mice. We have reported the efficient production of genome-edited mice using reproductive engineering techniques, such as ultra-superovulation, in vitro fertilization (IVF) and vitrification/warming of zygotes. We usually use vitrified/warmed fertilized oocytes created by IVF for microinjection because of work efficiency and flexible scheduling. Here, we investigated whether the culture time of zygotes before microinjection influences the efficiency of producing knock-in mice. Knock-in mice were generated using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system and single-stranded oligodeoxynucleotide (ssODN) or PITCh (Precise Integration into Target Chromosome) system, a method of integrating a donor vector assisted by microhomology-mediated end-joining. The cryopreserved fertilized oocytes were warmed, cultured for several hours and microinjected at different timings. Microinjection was performed with Cas9 protein, guide RNA(s), and an ssODN or PITCh donor plasmid for the ssODN knock-in and the PITCh knock-in, respectively. Different production efficiencies of knock-in mice were observed by changing the timing of microinjection. Our study provides useful information for the CRISPR-Cas9-based generation of knock-in mice. © 2017. Published by The Company of Biologists Ltd.

Knock-In Mice with NOP-eGFP Receptors Identify Receptor Cellular and Regional Localization.

Science.gov (United States)

Ozawa, Akihiko; Brunori, Gloria; Mercatelli, Daniela; Wu, Jinhua; Cippitelli, Andrea; Zou, Bende; Xie, Xinmin Simon; Williams, Melissa; Zaveri, Nurulain T; Low, Sarah; Scherrer, Grégory; Kieffer, Brigitte L; Toll, Lawrence

2015-08-19

The nociceptin/orphanin FQ (NOP) receptor, the fourth member of the opioid receptor family, is involved in many processes common to the opioid receptors including pain and drug abuse. To better characterize receptor location and trafficking, knock-in mice were created by inserting the gene encoding enhanced green fluorescent protein (eGFP) into the NOP receptor gene (Oprl1) and producing mice expressing a functional NOP-eGFP C-terminal fusion in place of the native NOP receptor. The NOP-eGFP receptor was present in brain of homozygous knock-in animals in concentrations somewhat higher than in wild-type mice and was functional when tested for stimulation of [(35)S]GTPγS binding in vitro and in patch-clamp electrophysiology in dorsal root ganglia (DRG) neurons and hippocampal slices. Inhibition of morphine analgesia was equivalent when tested in knock-in and wild-type mice. Imaging revealed detailed neuroanatomy in brain, spinal cord, and DRG and was generally consistent with in vitro autoradiographic imaging of receptor location. Multicolor immunohistochemistry identified cells coexpressing various spinal cord and DRG cellular markers, as well as coexpression with μ-opioid receptors in DRG and brain regions. Both in tissue slices and primary cultures, the NOP-eGFP receptors appear throughout the cell body and in processes. These knock-in mice have NOP receptors that function both in vitro and in vivo and appear to be an exceptional tool to study receptor neuroanatomy and correlate with NOP receptor function. The NOP receptor, the fourth member of the opioid receptor family, is involved in pain, drug abuse, and a number of other CNS processes. The regional and cellular distribution has been difficult to determine due to lack of validated antibodies for immunohistochemical analysis. To provide a new tool for the investigation of receptor localization, we have produced knock-in mice with a fluorescent-tagged NOP receptor in place of the native NOP receptor. These

Echocardiographic specrtrum of heart disease in a secondary ...

African Journals Online (AJOL)

HHD (58%) was the most common heart disease followed by dilated cardiomyopathy (7.4%) and valvular heart disease(6.1%).61(8.1%) subjects had normal echocardiogram. Conclusion:Hypertensive heart disease is the most common indication for echocardiography and also the predominant cause of heart disease in ...

Gold nanoparticle mediated laser transfection for efficient siRNA mediated gene knock down.

Directory of Open Access Journals (Sweden)

Dag Heinemann

Full Text Available Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types.

Gold nanoparticle mediated laser transfection for efficient siRNA mediated gene knock down.

Science.gov (United States)

Heinemann, Dag; Schomaker, Markus; Kalies, Stefan; Schieck, Maximilian; Carlson, Regina; Murua Escobar, Hugo; Ripken, Tammo; Meyer, Heiko; Heisterkamp, Alexander

2013-01-01

Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types.

Gold Nanoparticle Mediated Laser Transfection for Efficient siRNA Mediated Gene Knock Down

Science.gov (United States)

Heinemann, Dag; Schomaker, Markus; Kalies, Stefan; Schieck, Maximilian; Carlson, Regina; Escobar, Hugo Murua; Ripken, Tammo; Meyer, Heiko; Heisterkamp, Alexander

2013-01-01

Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types. PMID:23536802

Hyperoxic preconditioning fails to confer additional protection against ischemia-reperfusion injury in acute diabetic rat heart.

Science.gov (United States)

Pourkhalili, Khalil; Hajizadeh, Sohrab; Akbari, Zahra; Dehaj, Mansour Esmaili; Akbarzadeh, Samad; Alizadeh, Alimohammad

2012-01-01

Experimental studies show that detrimental effects of ischemia-reperfusion (I/R) injury can be attenuated by hyperoxic preconditioning in normal hearts, however, there are few studies about hyperoxia effects in diseased myocardium. The present study was designed to assess the cardioprotective effects of hyperoxia pretreatment (≥ 95 % O2) in acute diabetic rat hearts. Normal and one week acute diabetic rats were either exposed to 60 (H60) and 180 (H180) min of hyperoxia or exposed to normal atmospheric air (21 % O2). Then hearts were isolated immediately and subjected to 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size, cardiomyocyte apoptosis, enzymes release and ischemia induced arrhythmias were determined. Heart of diabetic control rats had less infarct size and decreased LDH and CK-MB release compared to normal hearts. 60 and 180 min of hyperoxia reduced myocardial infarct size and enzymes release in normal hearts. 180 min of hyperoxia also decreased cardiomyocytes apoptosis in normal state. On the other hand, protective values of hyperoxia were not significantly different in diabetic hearts. Moreover, hyperoxia reduced severity of ventricular arrhythmias in normal rat hearts whereas; it did not confer any additional antiarrhythmic protection in diabetic hearts. These findings suggest that diabetic hearts are less susceptible to ischemia-induced arrhythmias and infarction. Hyperoxia greatly protects rat hearts against I/R injury in normal hearts, however, it could not provide added cardioprotective effects in acute phase of diabetes.

Numerical analysis of knock during HCCI in a high compression ratio methanol engine based on LES with detailed chemical kinetics

International Nuclear Information System (INIS)

Zhen, Xudong; Wang, Yang

2015-01-01

Highlights: • Knock during HCCI in a high compression ratio methanol engine was modeled. • A detailed methanol mechanism was used to simulate the knocking combustion. • Compared with the SI engines, the HCCI knocking combustion burnt faster. • The reaction rate of HCO had two obvious peaks, one was positive, and another was negative. • Compared with the SI engines, the values of the reaction rates of CH 2 O, H 2 O 2 , and HO 2 were higher, and it had negative peaks. - Abstract: In this study, knock during HCCI (homogeneous charge compression ignition) was studied based on LES (large eddy simulation) with methanol chemical kinetics (84-reaction, 21-species) in a high compression ratio methanol engine. The non-knocking and knocking combustion of SI (spark ignition) and HCCI engines were compared. The results showed that the auto-ignition spots were initially occurred near the combustion chamber wall. The knocking combustion burnt faster during HCCI than SI methanol engine. The HCO reaction rate was different from SI engine, it had two obvious peaks, one was positive peak, and another was negative peak. Compared with the SI methanol engine, in addition to the concentration of HCO, the concentrations of the other intermediate products and species such as CO, OH, CH 2 O, H 2 O 2 , HO 2 were increased significantly; the reaction rates of CH 2 O, H 2 O 2 , and HO 2 had negative peaks, and whose values were several times higher than SI methanol engine

The Expression of TALEN before Fertilization Provides a Rapid Knock-Out Phenotype in Xenopus laevis Founder Embryos.

Science.gov (United States)

Miyamoto, Kei; Suzuki, Ken-Ichi T; Suzuki, Miyuki; Sakane, Yuto; Sakuma, Tetsushi; Herberg, Sarah; Simeone, Angela; Simpson, David; Jullien, Jerome; Yamamoto, Takashi; Gurdon, J B

2015-01-01

Recent advances in genome editing using programmable nucleases have revolutionized gene targeting in various organisms. Successful gene knock-out has been shown in Xenopus, a widely used model organism, although a system enabling less mosaic knock-out in founder embryos (F0) needs to be explored in order to judge phenotypes in the F0 generation. Here, we injected modified highly active transcription activator-like effector nuclease (TALEN) mRNA to oocytes at the germinal vesicle (GV) stage, followed by in vitro maturation and intracytoplasmic sperm injection, to achieve a full knock-out in F0 embryos. Unlike conventional injection methods to fertilized embryos, the injection of TALEN mRNA into GV oocytes allows expression of nucleases before fertilization, enabling them to work from an earlier stage. Using this procedure, most of developed embryos showed full knock-out phenotypes of the pigmentation gene tyrosinase and/or embryonic lethal gene pax6 in the founder generation. In addition, our method permitted a large 1 kb deletion. Thus, we describe nearly complete gene knock-out phenotypes in Xenopus laevis F0 embryos. The presented method will help to accelerate the production of knock-out frogs since we can bypass an extra generation of about 1 year in Xenopus laevis. Meantime, our method provides a unique opportunity to rapidly test the developmental effects of disrupting those genes that do not permit growth to an adult able to reproduce. In addition, the protocol shown here is considerably less invasive than the previously used host transfer since our protocol does not require surgery. The experimental scheme presented is potentially applicable to other organisms such as mammals and fish to resolve common issues of mosaicism in founders.

Sex Dimorphism of the Heart Diameters and Cardiothoracic Ratios ...

African Journals Online (AJOL)

Objective: To determine gender associated differences in the cardiothoracic ratio (CTR) and heart diameters in a normal Nigerian population. Subject and Method: The normal heart diameters and cardiothoracic ratios were measured from posteroanterior (PA) chest radiographs of healthy 510 male and 508 female ...

The relationship between phase and heart rate

International Nuclear Information System (INIS)

Underwood, S.R.; Walton, S.; Brown, N.J.G.; Laming, P.J.; Ell, P.J.; Emanuel, R.W.; Swanton, R.H.

1984-01-01

The Fourier phase image is used in rest and stress radionuclide angiocardiography to assess the timing of ventricular wall motion in a regional fashion, and areas of high phase are taken to reprensent areas of delayed contraction. However, phase increases with heart rate and this can make interpretation difficult. This study investigates the relationship between phase and heart rate. A heterogenous group of 43 subjects was studied by ECG-gated equilibrium radionuclide angiocardiography, all of the subjects having normal extent of left ventricular wall motion as judged by normal ejection fraction and normal amplitude image. Mean left ventricular phase correlated well with mean time of end systole (r=0.92), but there was no correlation with time of end diastole.Thus phase reflects the time of end systole as a proportion of cycle length and should be linearly related to heart rate provided the duration of systole is unchanged. In 28 normal subjects mean left ventricular phase correlated linearly with resting rate (r=0.91), and when exercised the relationship was maintained up to 90 beats per minute. Above this rate the increases were less marked as the duration of systole shortened. The same was true in 4 subjects paced at different rates. Mean resting heart rate in the normal subjects was 70 beats per minute and correcting phase linearly to rate 70 did not change mean left ventricular phase but did decrease the standard deviation from 18 degree to 12 degree. It is concluded that correcting phase for heart rate below 90 beats per minute will increase the sensitivity of the phase image to abnormalities of the timing of ventricular contraction. This correction should be appropriate in resting, isometric exercise, and cold pressor studies but because of the higher heart rates involved will not be appropriate for bicycle exercise. (Author)

Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity.

Science.gov (United States)

Monceau, Virginie; Pasinetti, Nadia; Schupp, Charlotte; Pouzoulet, Fred; Opolon, Paule; Vozenin, Marie-Catherine

2010-11-01

The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibrogenic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardiomyocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibrogenic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibrogenic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established

Educational series in congenital heart disease:Congenital left-sided heart obstruction

OpenAIRE

Carr, Michelle; Curtis, Stephanie; Marek, Jan

2018-01-01

Congenital obstruction of the left ventricular outflow tract remains a significant problem and multilevel obstruction can often coexist. Obstruction can take several morphological forms and may involve the subvalvar, valvar or supravalvar portion of the aortic valve complex. Congenital valvar stenosis presenting in the neonatal period represents a spectrum of disorders ranging from the hypoplastic left heart syndrome to almost normal hearts. Treatment options vary dependent on the severity of...

13C(α,n)16O reaction as the knock-out exchange process

International Nuclear Information System (INIS)

Kim, G.; Khajdarov, R.R.; Zaparov, Eh.A.

2000-01-01

S-factor for the 13 C(α,n) 16 O reaction is studied. In the framework of the simple phenomenological model this reaction is analysed as neutron knocked-out by α-particle exchange process. The analysis demonstrates the importance of taking into account 2p-state in 13 C. The 13 C(α,n) 16 O cross section is considered both as the knock-out exchange process and as it's combination with process through a compound nucleus. It was shown that for E α s value extrapolated to low energies is found to be noticeably larger that of R-matrix analysis. Different ways of improving the proposed model are discussed. (author)

(p, α) reactions: knock-on(out) or pick-up

International Nuclear Information System (INIS)

Gadioli, E.

1983-01-01

Nothwithstanding the great lot of data collected starting from the beginning of fifties, it cannot be said that a good degree of knowledge about the (p, α) reaction mechanism has been reached. Experimental data are usually interpreted or on the basis of a pure pick-up or knock-on(out) mechanism, though many results suggest the importance of both mechanism

NEUROTICISM PROFILE IN CORONARY HEART DISEASE

OpenAIRE

Bhargava, S. C.; Sharma, S. N.; Agarwal, B. V.

1980-01-01

SUMMARY Thirty seven cases of coronary heart disease and 30 normal healthy controls were administered Hindi version of MHQ. The coronary heart disease patients scored significantly higher on total neuroticism, free-floating anxiety and somatic anxiety subscales of MHQ.

Affecting Rhomboid-3 function causes a dilated heart in adult Drosophila.

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Lin Yu

2010-05-01

Full Text Available Drosophila is a well recognized model of several human diseases, and recent investigations have demonstrated that Drosophila can be used as a model of human heart failure. Previously, we described that optical coherence tomography (OCT can be used to rapidly examine the cardiac function in adult, awake flies. This technique provides images that are similar to echocardiography in humans, and therefore we postulated that this approach could be combined with the vast resources that are available in the fly community to identify new mutants that have abnormal heart function, a hallmark of certain cardiovascular diseases. Using OCT to examine the cardiac function in adult Drosophila from a set of molecularly-defined genomic deficiencies from the DrosDel and Exelixis collections, we identified an abnormally enlarged cardiac chamber in a series of deficiency mutants spanning the rhomboid 3 locus. Rhomboid 3 is a member of a highly conserved family of intramembrane serine proteases and processes Spitz, an epidermal growth factor (EGF-like ligand. Using multiple approaches based on the examination of deficiency stocks, a series of mutants in the rhomboid-Spitz-EGF receptor pathway, and cardiac-specific transgenic rescue or dominant-negative repression of EGFR, we demonstrate that rhomboid 3 mediated activation of the EGF receptor pathway is necessary for proper adult cardiac function. The importance of EGF receptor signaling in the adult Drosophila heart underscores the concept that evolutionarily conserved signaling mechanisms are required to maintain normal myocardial function. Interestingly, prior work showing the inhibition of ErbB2, a member of the EGF receptor family, in transgenic knock-out mice or individuals that received herceptin chemotherapy is associated with the development of dilated cardiomyopathy. Our results, in conjunction with the demonstration that altered ErbB2 signaling underlies certain forms of mammalian cardiomyopathy, suggest

Knock-Outs, Stick-Outs, Cut-Outs: Clipping Paths Separate Objects from Background.

Science.gov (United States)

Wilson, Bradley

1998-01-01

Outlines a six-step process that allows computer operators, using Photoshop software, to create "knock-outs" to precisely define the path that will serve to separate the object from the background. (SR)

Human thrombomodulin knock-in mice reveal differential effects of human thrombomodulin on thrombosis and atherosclerosis.

Science.gov (United States)

Raife, Thomas J; Dwyre, Denis M; Stevens, Jeff W; Erger, Rochelle A; Leo, Lorie; Wilson, Katina M; Fernández, Jose A; Wilder, Jennifer; Kim, Hyung-Suk; Griffin, John H; Maeda, Nobuyo; Lentz, Steven R

2011-11-01

We sought to develop a murine model to examine the antithrombotic and antiinflammatory functions of human thrombomodulin in vivo. Knock-in mice that express human thrombomodulin from the murine thrombomodulin gene locus were generated. Compared with wild-type mice, human thrombomodulin knock-in mice exhibited decreased protein C activation in the aorta (Pknock-in mice compared with wild-type mice (Pknock-in mice (12±3 minutes) than in wild-type mice (31±6 minutes; Pknock-in and wild-type mice after injection of endotoxin. When crossed with apolipoprotein E-deficient mice and fed a Western diet, knock-in mice had a further decrease in protein C activation but did not exhibit increased atherosclerosis. Expression of human thrombomodulin in place of murine thrombomodulin produces viable mice with a prothrombotic phenotype but unaltered responses to systemic inflammatory or atherogenic stimuli. This humanized animal model will be useful for investigating the function of human thrombomodulin under pathophysiological conditions in vivo.

Fascin-1 knock-down of human glioma cells reduces their microvilli/filopodia while improving their susceptibility to lymphocyte-mediated cytotoxicity

Science.gov (United States)

Hoa, Neil T; Ge, Lisheng; Erickson, Kate L; Kruse, Carol A; Cornforth, Andrew N; Kuznetsov, Yurii; McPherson, Alex; Martini, Filippo; Jadus, Martin R

2015-01-01

Cancer cells derived from Glioblastoma multiforme possess membranous protrusions allowing these cells to infiltrate surrounding tissue, while resisting lymphocyte cytotoxicity. Microvilli and filopodia are supported by actin filaments cross-linked by fascin. Fascin-1 was genetically silenced within human U251 glioma cells; these knock-down glioma cells lost their microvilli/filopodia. The doubling time of these fascin-1 knock-down cells was doubled that of shRNA control U251 cells. Fascin-1 knock-down cells lost their transmigratory ability responding to interleukin-6 or insulin-like growth factor-1. Fascin-1 silenced U251 cells were more easily killed by cytolytic lymphocytes. Fascin-1 knock-down provides unique opportunities to augment glioma immunotherapy by simultaneously targeting several key glioma functions: like cell transmigration, cell division and resisting immune responses. PMID:25901196

Cognition of normal pattern of myocardial polar map

International Nuclear Information System (INIS)

Fujisawa, Yasuo; Sasaki, Jiro; Kashima, Kenji; Matsumura, Yasushi; Yamamoto, Kazuhiro; Kodama, Kazuhisa

1989-01-01

When we diagnose the presence of ischemic heart disease by the diagrams of computer-generated polar map of exercised thallium images, the estimation of the presence of the deficit is not sufficient, because many normal subjects are considered as abnormal. The mean+2SD of defect severity index (DSI) of 118 normal subjects was 120, and we defined the patients with DSI≤120 as normal. But in 139 patients with their DSI≤120, 28 patients had significant coronary stenosis (>75%) and this means that false negative was 20%. We estimated the pattern of the deficit and found that in 109 of 111 subjects with normal coronary arteries, and 16 of 28 patients with ischemic heart disease, the patterns of the diagrams of polar map were patchy. This means that the diagram of the polar map show patchy pattern more frequently in normal subjects. In 125 patients whose diagrams of polar map were patchy, 16 patients with ischemic heart disease were included (false negative was 13%). We conclude that the estimation of DSI and the pattern of the diagram of polar map should be simultaneously considered and this makes the more accurate diagnosis possible. (author)

Systolic Strain Abnormalities to Predict Hospital Readmission in Patients With Heart Failure and Normal Ejection Fraction

Science.gov (United States)

Borer, Steven M.; Kokkirala, Aravind; O'Sullivan, David M.; Silverman, David I.

2011-01-01

Background Despite intensive investigation, the pathogenesis of heart failure with normal ejection fraction (HFNEF) remains unclear. We hypothesized that subtle abnormalities of systolic function might play a role, and that abnormal systolic strain and strain rate would provide a marker for adverse outcomes. Methods Patients of new CHF and left ventricular ejection fraction > 50% were included. Exclusion criteria were recent myocardial infarction, severe valvular heart disease, severe left ventricular hypertrophy (septum >1.8 cm), or a technically insufficient echocardiogram. Average peak systolic strain and strain rate were measured using an off-line grey scale imaging technique. Systolic strain and strain rate for readmitted patients were compared with those who remained readmission-free. Results One hundred consecutive patients with a 1st admission for HFNEF from January 1, 2004 through December 31, 2007, inclusive, were analyzed. Fifty two patients were readmitted with a primary diagnosis of heart failure. Systolic strain and strain rates were reduced in both study groups compared to controls. However, systolic strain did not differ significantly between the two groups (-11.7% for those readmitted compared with -12.9% for those free from readmission, P = 0.198) and systolic strain rates also were similar (-1.05 s-1 versus -1.09 s-1, P = 0.545). E/e’ was significantly higher in readmitted patients compared with those who remained free from readmission (14.5 versus 11.0, P = 0.013). E/e’ (OR 1.189, 95% CI 1.026-1.378; P = 0.021) was found to be an independent predictor for HFNEF readmission. Conclusions Among patients with new onset HFNEF, SS and SR rates are reduced compared with patients free of HFNEF, but do not predict hospital readmission. Elevated E/e’ is a predictor of readmission in these patients. PMID:28352395

Nuclear triiodothyronine receptors in rabbit heart

International Nuclear Information System (INIS)

Banerjee, S.K.; Ulrich, J.M.; Kaldor, G.J.

1986-01-01

Nuclear triiodothyronine receptors from rat liver have been characterized in detail by several investigators. However, little work has been done in this area using heart tissue. In this study they examined and characterized the triiodothyronine binding in rabbit hearts. Nuclei have been prepared from ventricular muscle cells of normal and thyrotoxic rabbits as well as from atrial muscle cells of normal rabbit. Hearts were perfused with a minimum essential medium containing collagenase and bovine serum albumin. Myocardial cells were isolated and then disrupted by sonication and washing with a Triton X-100 buffer solution. A discontinuous sucrose density gradient was then used to isolate the mycoardial nuclei. Radiolabelled triiodothyronine (T 3 ) binding to nuclei was examined using conditions described by established procedures. Scatchard analysis of the binding data yields maximum binding capacity (B/sub max/) of 0.17 +/- 0.2 pmol/mg DNA and apparent dissociation constant (K/sub d/) of 400 +/- 50 pM for normal heart T 3 -receptors. The apparent capacity for T 3 binding is approximately 40% greater in myocardial nuclei prepared from hearts of hyperthyroid rabbits. The binding capacity of atrial muscle nuclei is about fourfold lower than ventricular cell nuclei. The results suggest that binding capacity for T 3 -receptor in the atrium is considerably lower than that found in the ventricle

Effect of Nebivolol on MIBG Parameters and Exercise in Heart Failure with Normal Ejection Fraction

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Messias, Leandro Rocha, E-mail: lmessias@cardiol.br; Ferreira, Aryanne Guimarães; Miranda, Sandra Marina Ribeiro de; Teixeira, José Antônio Caldas [Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Azevedo, Jader Cunha de [Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Hospital Procardíaco, Rio de Janeiro, RJ (Brazil); Messias, Ana Carolina Nader Vasconcelos [Hospital Federal dos Servidores do Estado do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Maróstica, Elisabeth [Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Mesquita, Claudio Tinoco [Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Hospital Procardíaco, Rio de Janeiro, RJ (Brazil)

2016-05-15

More than 50% of the patients with heart failure have normal ejection fraction (HFNEF). Iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy and cardiopulmonary exercise test (CPET) are prognostic markers in HFNEF. Nebivolol is a beta-blocker with vasodilating properties. To evaluate the impact of nebivolol therapy on CPET and123I-MIBG scintigraphic parameters in patients with HFNEF. Twenty-five patients underwent 123I-MIBG scintigraphy to determine the washout rate and early and late heart-to-mediastinum ratios. During the CPET, we analyzed the systolic blood pressure (SBP) response, heart rate (HR) during effort and recovery (HRR), and oxygen uptake (VO{sub 2}). After the initial evaluation, we divided our cohort into control and intervention groups. We then started nebivolol and repeated the tests after 3 months. After treatment, the intervention group showed improvement in rest SBP (149 mmHg [143.5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0.016]), rest HR (78 bpm [65.5-84 bpm] versus 64.5 bpm [57.5-75.5 bpm, p = 0.028]), peak SBP (235 mmHg [216.5-249 mmHg] versus 198 mmHg [191-220.5 mmHg], p = 0.001), peak HR (124.5 bpm [115-142 bpm] versus 115 bpm [103.7-124 bpm], p= 0.043), HRR on the 1st minute (6.5 bpm [4.75-12.75 bpm] versus 14.5 bpm [6.7-22 bpm], p = 0.025) and HRR on the 2nd minute (15.5 bpm [13-21.75 bpm] versus 23.5 bpm [16-31.7 bpm], p = 0.005), but no change in peak VO{sub 2} and 123I-MIBG scintigraphic parameters. Despite a better control in SBP, HR during rest and exercise, and improvement in HRR, nebivolol failed to show a positive effect on peak VO2 and 123I-MIBG scintigraphic parameters. The lack of effect on adrenergic activity may be the cause of the lack of effect on functional capacity.

Effect of Nebivolol on MIBG Parameters and Exercise in Heart Failure with Normal Ejection Fraction

International Nuclear Information System (INIS)

Messias, Leandro Rocha; Ferreira, Aryanne Guimarães; Miranda, Sandra Marina Ribeiro de; Teixeira, José Antônio Caldas; Azevedo, Jader Cunha de; Messias, Ana Carolina Nader Vasconcelos; Maróstica, Elisabeth; Mesquita, Claudio Tinoco

2016-01-01

More than 50% of the patients with heart failure have normal ejection fraction (HFNEF). Iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy and cardiopulmonary exercise test (CPET) are prognostic markers in HFNEF. Nebivolol is a beta-blocker with vasodilating properties. To evaluate the impact of nebivolol therapy on CPET and123I-MIBG scintigraphic parameters in patients with HFNEF. Twenty-five patients underwent 123I-MIBG scintigraphy to determine the washout rate and early and late heart-to-mediastinum ratios. During the CPET, we analyzed the systolic blood pressure (SBP) response, heart rate (HR) during effort and recovery (HRR), and oxygen uptake (VO 2 ). After the initial evaluation, we divided our cohort into control and intervention groups. We then started nebivolol and repeated the tests after 3 months. After treatment, the intervention group showed improvement in rest SBP (149 mmHg [143.5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0.016]), rest HR (78 bpm [65.5-84 bpm] versus 64.5 bpm [57.5-75.5 bpm, p = 0.028]), peak SBP (235 mmHg [216.5-249 mmHg] versus 198 mmHg [191-220.5 mmHg], p = 0.001), peak HR (124.5 bpm [115-142 bpm] versus 115 bpm [103.7-124 bpm], p= 0.043), HRR on the 1st minute (6.5 bpm [4.75-12.75 bpm] versus 14.5 bpm [6.7-22 bpm], p = 0.025) and HRR on the 2nd minute (15.5 bpm [13-21.75 bpm] versus 23.5 bpm [16-31.7 bpm], p = 0.005), but no change in peak VO 2 and 123I-MIBG scintigraphic parameters. Despite a better control in SBP, HR during rest and exercise, and improvement in HRR, nebivolol failed to show a positive effect on peak VO2 and 123I-MIBG scintigraphic parameters. The lack of effect on adrenergic activity may be the cause of the lack of effect on functional capacity

Generation of beta-lactoglobulin knock-out goats using CRISPR/Cas9.

Directory of Open Access Journals (Sweden)

Wenjun Zhou

Full Text Available Goat's milk, considered a substitute for cow's milk, has a high nutritional value. However, goat's milk contains various allergens, predominantly β-lactoglobulin (BLG. In this study, we employed the CRISPR/Cas9 system to target the BLG locus in goat fibroblasts for sgRNA optimization and generate BLG knock-out goats through co-injection of Cas9 mRNA and small guide RNAs (sgRNAs into goat embryos at the one-cell stage. We firstly tested sgRNA editing efficiencies in goat fibroblast cells, and approximately 8.00%-9.09% of the cells were modified in single sgRNA-guided targeting experiment. Among the kids, the genome-targeting efficiencies of single sgRNA were 12.5% (10 ng/μL sg1 and 0% (10 ng/μL sg2 and efficiencies of dual sgRNAs were 25.0% (25 ng/μL sg2+sg3 group and 28.6% (50 ng/μL sg2+sg3 group. Relative expression of BLG in BLG knock-out goat mammary glands significantly (p < 0.01 decreased as well as other milk protein coding genes, such as CSN1S1, CSN1S2, CSN2, CSN3 and LALBA (p < 0.05. As expected, BLG protein had been abolished in the milk of the BLG knock-out goat. In addition, most of the targeted kids were chimeric (3/4, and their various body tissues were edited simultaneously. Our study thus provides a basis for optimizing the quality of goat milk, which can be applied to biomedical and agricultural research.

Efficient generation of Rosa26 knock-in mice using CRISPR/Cas9 in C57BL/6 zygotes.

Science.gov (United States)

Chu, Van Trung; Weber, Timm; Graf, Robin; Sommermann, Thomas; Petsch, Kerstin; Sack, Ulrike; Volchkov, Pavel; Rajewsky, Klaus; Kühn, Ralf

2016-01-16

The CRISPR/Cas9 system is increasingly used for gene inactivation in mouse zygotes, but homology-directed mutagenesis and use of inbred embryos are less established. In particular, Rosa26 knock-in alleles for the insertion of transgenes in a genomic 'safe harbor' site, have not been produced. Here we applied CRISPR/Cas9 for the knock-in of 8-11 kb inserts into Rosa26 of C57BL/6 zygotes. We found that 10-20 % of live pups derived from microinjected zygotes were founder mutants, without apparent off-target effects, and up to 50 % knock-in embryos were recovered upon coinjection of Cas9 mRNA and protein. Using this approach, we established a new mouse line for the Cre/loxP-dependent expression of Cas9. Altogether, our protocols and resources support the fast and direct generation of new Rosa26 knock-in alleles and of Cas9-mediated in vivo gene editing in the widely used C57BL/6 inbred strain.

Targeted Knock-Down of miR21 Primary Transcripts Using snoMEN Vectors Induces Apoptosis in Human Cancer Cell Lines.

Directory of Open Access Journals (Sweden)

Motoharu Ono

Full Text Available We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2.

Targeted Knock-Down of miR21 Primary Transcripts Using snoMEN Vectors Induces Apoptosis in Human Cancer Cell Lines.

Science.gov (United States)

Ono, Motoharu; Yamada, Kayo; Avolio, Fabio; Afzal, Vackar; Bensaddek, Dalila; Lamond, Angus I

2015-01-01

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2.

The Effects of Engine Speed and Mixture Temperature on the Knocking Characteristics of Several Fuels

Science.gov (United States)

Lee, Dana W

1940-01-01

Six 100-octane and two 87-octane aviation engine fuels were tested in a modified C.F.R. variable-compression engine at 1,500, 2,000 and 2,500 rpm. The mixture temperature was raised from 50 to 300 F in approximately 50 degree steps and, at each temperature, the compression ratio was adjusted to give incipient knock as shown by a cathode ray indicator. The results are presented in tabular form. The results are analyzed on the assumption that the conditions which determine whether a given fuel will knock are the maximum values of density and temperature reached by the burning gases. A maximum permissible density factor, proportional to the maximum density of the burning gases just prior to incipient knock, and the temperature of the burning gases at that time were computed for each of the test conditions. Values of the density factors were plotted against the corresponding end-gas temperatures for the three engine speeds and also against engine speed for several and end-gas temperatures. The maximum permissible density factor varied only slightly with engine speed but decreased rapidly with an increase in the end-gas temperature. The effect of changing the mixture temperature was different for fuels of different types. The results emphasize the desirability of determining the anti knock values of fuels over a wide range of engine and intake-air conditions rather that at a single set of conditions.

Highly efficient generation of knock-in transgenic medaka by CRISPR/Cas9-mediated genome engineering.

Science.gov (United States)

Watakabe, Ikuko; Hashimoto, Hisashi; Kimura, Yukiko; Yokoi, Saori; Naruse, Kiyoshi; Higashijima, Shin-Ichi

2018-01-01

Medaka ( Oryzias latipes ) is a popular animal model used in vertebrate genetic analysis. Recently, an efficient (~ 30%) knock-in system via non-homologous end joining (NHEJ) was established in zebrafish using the CRISPR/Cas9 system. If the same technique were applicable in medaka, it would greatly expand the usefulness of this model organism. The question of the applicability of CRISPR/Cas9 in medaka, however, has yet to be addressed. We report the highly efficient generation of knock-in transgenic medaka via non-homologous end joining (NHEJ). Donor plasmid containing a heat-shock promoter and a reporter gene was co-injected with a short guide RNA (sgRNA) targeted for genome digestion, an sgRNA targeted for donor plasmid digestion, and Cas9 mRNA. Broad transgene expression in the expression domain of a target gene was observed in approximately 25% of injected embryos. By raising these animals, we established stable knock-in transgenic fish with several different constructs for five genetic loci, obtaining transgenic founders at efficiencies of > 50% for all five loci. Further, we show that the method is useful for obtaining mutant alleles. In the experiments where transgene integrations were targeted between the transcription start site and the initiation methionine, the resultant transgenic fish became mutant alleles. With its simplicity, design flexibility, and high efficiency, we propose that CRISPR/Cas9-mediated knock-in via NHEJ will become a standard method for the generation of transgenic and mutant medaka.

A Simple Retroelement Based Knock-Down System in Dictyostelium: Further Insights into RNA Interference Mechanisms.

Science.gov (United States)

Friedrich, Michael; Meier, Doreen; Schuster, Isabelle; Nellen, Wolfgang

2015-01-01

We have previously shown that the most abundant Dictyostelium discoideum retroelement DIRS-1 is suppressed by RNAi mechanisms. Here we provide evidence that both inverted terminal repeats have strong promoter activity and that bidirectional expression apparently generates a substrate for Dicer. A cassette containing the inverted terminal repeats and a fragment of a gene of interest was sufficient to activate the RNAi response, resulting in the generation of ~21 nt siRNAs, a reduction of mRNA and protein expression of the respective endogene. Surprisingly, no transitivity was observed on the endogene. This was in contrast to previous observations, where endogenous siRNAs caused spreading on an artificial transgene. Knock-down was successful on seven target genes that we examined. In three cases a phenotypic analysis proved the efficiency of the approach. One of the target genes was apparently essential because no knock-out could be obtained; the RNAi mediated knock-down, however, resulted in a very slow growing culture indicating a still viable reduction of gene expression. ADVANTAGES OF THE DIRS-1–RNAI SYSTEM: The knock-down system required a short DNA fragment (~400 bp) of the target gene as an initial trigger. Further siRNAs were generated by RdRPs since we have shown some siRNAs with a 5'-triphosphate group. Extrachromosomal vectors facilitate the procedure and allowed for molecular and phenotypic analysis within one week. The system provides an efficient and rapid method to reduce protein levels including those of essential genes.

Classification of caesarean section and normal vaginal deliveries using foetal heart rate signals and advanced machine learning algorithms.

Science.gov (United States)

Fergus, Paul; Hussain, Abir; Al-Jumeily, Dhiya; Huang, De-Shuang; Bouguila, Nizar

2017-07-06

Visual inspection of cardiotocography traces by obstetricians and midwives is the gold standard for monitoring the wellbeing of the foetus during antenatal care. However, inter- and intra-observer variability is high with only a 30% positive predictive value for the classification of pathological outcomes. This has a significant negative impact on the perinatal foetus and often results in cardio-pulmonary arrest, brain and vital organ damage, cerebral palsy, hearing, visual and cognitive defects and in severe cases, death. This paper shows that using machine learning and foetal heart rate signals provides direct information about the foetal state and helps to filter the subjective opinions of medical practitioners when used as a decision support tool. The primary aim is to provide a proof-of-concept that demonstrates how machine learning can be used to objectively determine when medical intervention, such as caesarean section, is required and help avoid preventable perinatal deaths. This is evidenced using an open dataset that comprises 506 controls (normal virginal deliveries) and 46 cases (caesarean due to pH ≤ 7.20-acidosis, n = 18; pH > 7.20 and pH machine-learning algorithms are trained, and validated, using binary classifier performance measures. The findings show that deep learning classification achieves sensitivity = 94%, specificity = 91%, Area under the curve = 99%, F-score = 100%, and mean square error = 1%. The results demonstrate that machine learning significantly improves the efficiency for the detection of caesarean section and normal vaginal deliveries using foetal heart rate signals compared with obstetrician and midwife predictions and systems reported in previous studies.

Threshold bubble chamber for measurement of knock-on DT neutron tails from magnetic and inertial confinement experiments

International Nuclear Information System (INIS)

Fisher, R.K.; Zaveryaev, V.S.; Trusillo, S.V.

1996-07-01

We propose a new open-quotes thresholdclose quotes bubble chamber detector for measurement of knock-on neutron tails. These energetic neutrons result from fusion reactions involving energetic fuel ions created by alpha knock-on collisions in tokamak and other magnetic confinement experiments, and by both alpha and neutron knock-on collisions in inertial confinement fusion (ICF) experiments. The energy spectrum of these neutrons will yield information on the alpha population and energy distribution in tokamaks, and on alpha target physics and ρR measurements in ICF experiments. The bubble chamber should only detect neutrons with energies above a selectable threshold energy controlled by the bubble chamber pressure. The bubble chamber threshold mechanism, detection efficiency, and proposed applications to the International Thermonuclear Experimental Reactor (ITER) and National Ignition Facility (NIF) experiments will be discussed

When Your Back Hurts: Don't Let Back Pain Knock You Flat

Science.gov (United States)

... Your Back Hurts Don’t Let Back Pain Knock You Flat En español Send us your comments ... Complementary Health Approaches Halt the Hurt! References The SPORT Value Compass: Do the Extra Costs of Undergoing ...

A Knock at the Door. The Oryx Multicultural Folktale Series.

Science.gov (United States)

Shannon, George, Comp.

This folktales collection includes 35 versions, representing countries and cultures from around the world, of the traditional tale in which a dangerous character knocks at the door and tries to trick the children into letting him inside. The stories are intended for use in homes, schools, and libraries by both children and adults who enjoy sharing…

Moving frames for heart fiber geometry

DEFF Research Database (Denmark)

Piuze, Emmanuel; Sporring, Jon; Siddiqi, Kaleem

2013-01-01

fibers is central to our understanding of normal heart function. Motivated by a recent abstraction by Savadjiev et al. of heart wall fibers into generalized helicoid minimal surfaces, this paper develops an extension based on differential forms. The key idea is to use Maurer-Cartan’s method of moving...

Hematopoiesis in 5-Fluorouracil-Treated Adenosine A(3) Receptor Knock-Out Mice

Czech Academy of Sciences Publication Activity Database

Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Komůrková, Denisa

2015-01-01

Roč. 64, č. 2 (2015), s. 255-262 ISSN 0862-8408 Institutional support: RVO:68081707 Keywords : Adenosine A(3) receptor knock-out mice * Hematopoiesis * 5-fluorouracil-induced hematotoxicity Subject RIV: BO - Biophysics Impact factor: 1.643, year: 2015

Threshold bubble chamber for measurement of knock-on DT neutron tails from magnetic and inertial confinement experiments

International Nuclear Information System (INIS)

Fisher, R.K.; Zaveryaev, V.S.; Trusillo, S.V.

1997-01-01

We propose a new open-quotes thresholdclose quotes bubble chamber detector for measurement of knock-on neutron tails. These energetic neutrons result from fusion reactions involving energetic fuel ions created by alpha knock-on collisions in tokamak and other magnetic confinement experiments, and by both alpha and neutron knock-on collisions in inertial confinement fusion (ICF) experiments. The energy spectrum of these neutrons will yield information on the alpha population and energy distribution in tokamaks, and on alpha target physics and ρR measurements in ICF experiments. The bubble chamber should only detect neutrons with energies above a selectable threshold energy controlled by the bubble chamber pressure. The bubble chamber threshold mechanism, detection efficiency, and proposed applications to the International Thermonuclear Experimental Reactor and National Ignition Facility experiments will be discussed. copyright 1997 American Institute of Physics

Parametric images evaluation of selected phases of the heart cycle with PET

International Nuclear Information System (INIS)

Just, U.; Will, E.; Beuthien Baumann, B.; Bredow, J.

2002-01-01

The standard evaluation of dynamic heart acquisitions with PET uses image data not corrected for heart wall movement. The evaluation of parametric data sets (Patlak Plot) was investigated for gated studies of selected heart phases (diastolic, systolic) and compared to the standard evaluation. Parametric images of selected heart phases have improved resolution. The values for metabolic rate are different for a ''normal'' and gated evaluation, up to 50% more for the systole compared to the normal one. (orig.)

Modulation of the ρ/rock pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity

International Nuclear Information System (INIS)

Monceau, V.; Pasinetti, N.; Schupp, C.; Pouzoulet, F.; Opolon, P.; Vozenin, M.C.

2010-01-01

The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibro-genic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardio-myocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibro-genic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibro-genic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of

P-glycoprotein interaction with risperidone and 9-OH-risperidone studied in vitro, in knock-out mice and in drug-drug interaction experiments

DEFF Research Database (Denmark)

Ejsing, Thomas B.; Pedersen, Anne D.; Linnet, Kristian

2005-01-01

P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice......P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice...

Heart malformation induced by ionizing irradiation in rat embryo

International Nuclear Information System (INIS)

Higo, Hiromi; Satow, Yukio; Lee, Juing-Yi; Higo, Ken-ichi

1986-01-01

Proteins were extracted from morphologically abnormal heart induced by gamma-irradiation, and fractionated into the soluble and the insoluble (''muscle structural proteins'') fractions. Protein compositions of these fractions were examined by O'Farrell's two-dimensional polyacrylamide gel electrophoresis, and also by non-equilibrium pH gradient electrophoresis. The protein patterns thus obtained were then compared with those of the normal heart. Among about 450 major protein species observed, no significant difference was detected between normal and abnormal hearts as to the intensity and the location of the protein spots. Several minor protein species were found varying among the samples examined, but their relevance to the heart malformation are not clear at present. (author)

XYLITOL IMPROVES ANTI-OXIDATIVE DEFENSE SYSTEM IN SERUM, LIVER, HEART, KIDNEY AND PANCREAS OF NORMAL AND TYPE 2 DIABETES MODEL OF RATS.

Science.gov (United States)

Chukwuma, Chika Ifeanyi; Islam, Shahidul

2017-05-01

The present study investigated the anti-oxidative effects of xylitol both in vitro and in vivo in normal and type 2 diabetes (T2D) rat model. Free radical scavenging and ferric reducing potentials of different concentrations of xylitol were investigated in vitro. For in vivo study, six weeks old male Sprague-Dawley rats were divided into four groups, namely: Normal Control (NC), Diabetic Control (DBC), Normal Xylitol (NXYL) and Diabetic Xylitol (DXYL). T2D was induced in the DBC and DXYL groups. After the confirmation of diabetes, a 10% xylitol solution was supplied instead of drinking water to NXYL and DXYL, while normal drinking water was supplied to NC and DBC ad libitum. After five weeks intervention period, the animals were sacri- ficed and thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) concentrations as well as superoxide dismutase, catalase glutathione reductase and glutathione peroxidase activities were determined in the liver, heart, kidney, pancreatic tissues and serum samples. Xylitol exhibited significant (p foods and food products.

Cardiac damage in athlete's heart: When the "supernormal" heart fails!

Science.gov (United States)

Carbone, Andreina; D'Andrea, Antonello; Riegler, Lucia; Scarafile, Raffaella; Pezzullo, Enrica; Martone, Francesca; America, Raffaella; Liccardo, Biagio; Galderisi, Maurizio; Bossone, Eduardo; Calabrò, Raffaele

2017-06-26

Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete's blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete's heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded.

Heart rate variability and QT dispersion study in brain death patients and comatose patients with normal brainstem function

International Nuclear Information System (INIS)

Vakilian, A.R.; Iranmanesh, F.; Nadimi, A.E.; Kahnali, J.A.

2011-01-01

To compare heart rate variability (HRV) and QT dispersion in comatose patients with normal brainstem function and with brain death. Fourteen brain death patients with clinical signs of imminent brain death and 15 comatose patients were examined by neurologist in intensive care unit. HRV, RR interval and QT dispersion on ECG were assessed for 24 hours in both groups. Independent t-test and chi-square test were used for statistical analysis to determine significance which was set at p < 0.05. According to Holter findings, mean of standard deviation of RR-interval in the comatose and brain death groups was 48.33 and 35 respectively (p = 0.045). Mean of covariance coefficient of RR-interval was 0.065 in the comatose group and 0.043 in the brain deaths (p = 0.006). QT dispersion was not significant difference in two groups. HRV and RR-interval analysis appeared as an early finding for the diagnosis of brainstem death in comparison to comatose patients with normal brainstem function. QT dispersion had not significant in this regard. (author)

Nuclear magnetic resonance imaging of the heart

International Nuclear Information System (INIS)

Smolorz, J.; Linden, A.; Schicha, H.; Sechtem, U.

1988-01-01

NMR imaging is a noninvasive technique that has been shown to provide high-quality images of the heart. Due to the signal characteristics of flowing blood, inherent contrast between blood pool and myocardium is achieved without the use of contrast media. This paper briefly describes technical aspects of NMR imaging of the heart, normal cardiovascular anatomy, applications of the technique in patients with ischemic heart disease, and the potential of NMR imaging for functional studies in various forms of heart disease. (orig.)

Caracterización del 'Knock out' en Boxeo

OpenAIRE

Pic-Aguilar, Miguel; Sánchez-López, Carmen R.; Blanco Villaseñor, Ángel

2016-01-01

El objetivo de este trabajo es identificar las cuatro últimas acciones motrices emitidas (golpes) por boxeadores campeones del mundo de los pesos pesados y así poder caracterizar el 'Knock out' en boxeo. Para ello, hemos desarrollado una herramienta de observación que consta de cuatro criterios y 35 categorías. Para la selección de la muestra se tuvo en cuenta dos requisitos: haberse proclamado campeón del mundo del peso pesado durante el período que comprende 1921-2007 (desde Jack Dempsey ha...

Mosquito knock-down and adulticidal activities of essential oils by vaporizer, impregnated filter paper and aerosol methods

Directory of Open Access Journals (Sweden)

M. Ramar

2014-09-01

Full Text Available Essential oils from 12 medicinal plants were evaluated by three different bioassay methods (Vaporizer, Filter paper and Aerosol for Knock-down and adulticidal efficacy on the filarial vector mosquito, Culex quinquefasciatus. Based on screening results the effective plants were selected for investigating Knock-down and adulticidal potential against adult female of the laboratory-reared mosquito species, Cx. quinquefasciatus. In vaporizer bioassay method four different doses (1.25, 2.5, 5 and 10% were used. Four different doses (0.625, 1.25, 2.5 and 10% were used both filter paper (cm2 and aerosol (cm3 bioassay methods. Five essential oils (calamus, camphor, citronella, clove and eucalyptus were identified as potential treatments in vaporizer bioassay. The result showed that the knock down time decreased with increased concentration in clove oil treatment; the Knock-down time (KT 50 = 46.1 ± 0.1, 38.5 ± 0.1, 30.7 ± 0.2, and 20.1 ± 0.1 minutes was recorded at 1.25, 2.5, 5 and 10% /cm3 respectively. In filter paper method nine essential oils were identified as potential treatments. After 1 hr exposure period clove oil recorded the lowest median Knock-down time (KT50 which was calculated as 9.15 ± 0.1min/cm2. Followed by citronella (KT50 =11.4 ± 0.1 min and eucalyptus (KT50 =11.4 ±0.1min oils since they recorded lower median Knock-down time. All the twelve essential oils were identified as potential treatments in aerosol activity. The lethal time decreased when the concentration increased. At 5 % concentration the median lethal time (LT50 for clove oil was calculated as (LT50=3.80 ± 0.1minutes. The Cinnamon oil was effective which recorded (LT50 = 1.99 mins as median lethal time. Camphor (LT50 =19.6± 0.1 min oil were found to be less toxic by aerosol method. These results suggest that clove oil and cinnamon oil have the potential to be used as a eco-friendly approach for the control of the major important filaria vector Cx. quinquefasciatus

New Trends in Heart Regeneration: A Review

Directory of Open Access Journals (Sweden)

Kochegarov A

2016-11-01

Full Text Available In this review, we focus on new approaches that could lead to the regeneration of heart muscle and the restoration of cardiac muscle function derived from newly-formed cardiomyocytes. Various strategies for the production of cardiomyocytes from embryonic stem cells, induced pluripotent stem cells, adult bone marrow stem cells and cardiac spheres from human heart biopsies are described. Pathological conditions which lead to atherosclerosis and coronary artery disease often are followed by myocardial infarction causing myocardial cell death. After cell death, there is very little self-regeneration of the cardiac muscle tissue, which is replaced by non-contractile connective tissue, thus weakening the ability of the heart muscle to contract fully and leading to heart failure. A number of experimental research approaches to stimulate heart muscle regeneration with the hope of regaining normal or near normal heart function in the damaged heart muscle have been attempted. Some of these very interesting studies have used a variety of stem cell types in combination with potential cardiogenic differentiation factors in an attempt to promote differentiation of new cardiac muscle for possible future use in the clinical treatment of patients who have suffered heart muscle damage from acute myocardial infarctions or related cardiovascular diseases. Although progress has been made in recent years relative to promoting the differentiation of cardiac muscle tissue from non-muscle cells, much work remains to be done for this technology to be used routinely in translational clinical medicine to treat patients with damaged heart muscle tissue and return such individuals to pre-heart-attack activity levels.

Early Embryonic Heart Rate in Normal Pregnancies In Memory of ...

African Journals Online (AJOL)

To determine the appearance and development of embryonic heart rate a total of n = 317 Nigerian pregnant women were studied in the very early pregnancy from 23 – 56 days from the onset of last menstrual period (LMP). All pregnancies had a subsequent successful outcome. Transvaginal ultrasonography was ...

Complete inhibition of creatine kinase in isolated perfused rat hearts

International Nuclear Information System (INIS)

Fossel, E.T.; Hoefeler, H.

1987-01-01

Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts are able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. 31 P-NMR of the heart was carried out

Generation and characterization of PDGFRα-GFPCreERT2 knock-In mouse line.

Science.gov (United States)

Miwa, Hiroyuki; Era, Takumi

2015-05-01

Platelet-derived growth factor (PDGF) and its receptor play an important role in embryogenesis. PDGF receptor α (PDGFRα) is expressed specifically in the embryonic day 7.5 (E7.5) mesoderm and in the E9.5 neural crest among other tissues. PDGFRα-expressing cells and their descendants are involved in the formation of various tissues. To trace PDGFRα-expressing cells in vivo, we generated a knock-in mouse line that expressed a fusion protein of green fluorescent protein (GFP), Cre recombinase (Cre), and mutated estrogen receptor ligand-binding domain (ERT2) under the control of the PDGFRα promoter. In these mice, Cre activity in PDGFRα-expressing cells could be induced by tamoxifen treatment. Taken together, our results suggest that the knock-in mouse line generated here could be useful for studying PDGFRα-expressing cells and their descendants in vivo at various stages of development. © 2015 Wiley Periodicals, Inc.

CRISPR/Cas9-mediated knock-in of an optimized TetO repeat for live cell imaging of endogenous loci.

Science.gov (United States)

Tasan, Ipek; Sustackova, Gabriela; Zhang, Liguo; Kim, Jiah; Sivaguru, Mayandi; HamediRad, Mohammad; Wang, Yuchuan; Genova, Justin; Ma, Jian; Belmont, Andrew S; Zhao, Huimin

2018-06-15

Nuclear organization has an important role in determining genome function; however, it is not clear how spatiotemporal organization of the genome relates to functionality. To elucidate this relationship, a method for tracking any locus of interest is desirable. Recently clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) or transcription activator-like effectors were adapted for imaging endogenous loci; however, they are mostly limited to visualization of repetitive regions. Here, we report an efficient and scalable method named SHACKTeR (Short Homology and CRISPR/Cas9-mediated Knock-in of a TetO Repeat) for live cell imaging of specific chromosomal regions without the need for a pre-existing repetitive sequence. SHACKTeR requires only two modifications to the genome: CRISPR/Cas9-mediated knock-in of an optimized TetO repeat and its visualization by TetR-EGFP expression. Our simplified knock-in protocol, utilizing short homology arms integrated by polymerase chain reaction, was successful at labeling 10 different loci in HCT116 cells. We also showed the feasibility of knock-in into lamina-associated, heterochromatin regions, demonstrating that these regions prefer non-homologous end joining for knock-in. Using SHACKTeR, we were able to observe DNA replication at a specific locus by long-term live cell imaging. We anticipate the general applicability and scalability of our method will enhance causative analyses between gene function and compartmentalization in a high-throughput manner.

Comparison of frequencies of left ventricular systolic and diastolic heart failure in Chinese living in Hong Kong.

Science.gov (United States)

Yip, G W; Ho, P P; Woo, K S; Sanderson, J E

1999-09-01

There is a wide variation (13% to 74%) in the reported prevalence of heart failure associated with normal left ventricular (LV) systolic function (diastolic heart failure). There is no published information on this condition in China. To ascertain the prevalence of diastolic heart failure in this community, 200 consecutive patients with the typical features of congestive heart failure were studied with standard 2-dimensional Doppler echocardiography. A LV ejection fraction (LVEF) >45% was considered normal. The results showed that 12.5% had significant valvular heart disease. Of the remaining 175 patients, 132 had a LVEF >45% (75%). Therefore, 66% of patients with a clinical diagnosis of heart failure had a normal LVEF. Heart failure with normal LV systolic function was more common than systolic heart failure in those >70 years old (65% vs 47%; p = 0.015). Most (57%) had an abnormal relaxation pattern in diastole and 14% had a restrictive filling pattern. In the systolic heart failure group, a restrictive filling pattern was more common (46%). There were no significant differences in the sex distribution, etiology, or prevalence of LV hypertrophy between these 2 heart failure groups. In conclusion, heart failure with a normal LVEF or diastolic heart failure is more common than systolic heart failure in Chinese patients with the symptoms of heart failure. This may be related to older age at presentation and the high prevalence of hypertension in this community.

Holiday season for a healthy heart.

Science.gov (United States)

Stamps, Deborah C; Carr, Marcella L

2012-12-01

The term "holiday heart" is defined as an acute cardiac arrhythmia or conduction disturbance associated with heavy alcohol intake in individuals with no known heart disease, but in whom heart rhythm is restored to normal with abstinence of alcohol. This article provides a brief overview of the literature on this topic, discusses causes of increased cardiac events during the holiday season, describes a patient profile and the effect on patients' health as well as on their families, and provides suggestions to decrease the risk of holiday heart during the festive season. Copyright © 2012 Elsevier Inc. All rights reserved.

Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation.

Science.gov (United States)

Lundgren, Jakob; Sandqvist, Anna; Hedeland, Mikael; Bondesson, Ulf; Wikström, Gerhard; Rådegran, Göran

2018-04-12

Endothelial function, including the nitric oxide (NO)-pathway, has previously been extensively investigated in heart failure (HF). In contrast, studies are lacking on the NO pathway after heart transplantation (HT). We therefore investigated substances in the NO pathway prior to and after HT in relation to hemodynamic parameters. 12 patients (median age 50.0 yrs, 2 females), heart transplanted between June 2012 and February 2014, evaluated at our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months after HT were included. All patients had normal left ventricular function post-operatively and none had post-operative pulmonary hypertension or acute cellular rejection requiring therapy at the evaluations. Plasma concentrations of ADMA, SDMA, L-Arginine, L-Ornithine and L-Citrulline were analyzed at each evaluation. In comparison to controls, the plasma L-Arginine concentration was low and ADMA high in HF patients, resulting in low L-Arginine/ADMA-ratio pre-HT. Already four weeks after HT L-Arginine was normalized whereas ADMA remained high. Consequently the L-Arginine/ADMA-ratio improved, but did not normalize. The biomarkers remained unchanged at the six-month evaluation and the L-Arginine/ADMA-ratio correlated inversely to pulmonary vascular resistance (PVR) six months post-HT. Plasma L-Arginine concentrations normalize after HT. However, as ADMA is unchanged, the L-Arginine/ADMA-ratio remained low and correlated inversely to PVR. Together these findings suggest that (i) the L-Arginine/ADMA-ratio may be an indicator of pulmonary vascular tone after HT, and that (ii) NO-dependent endothelial function is partly restored after HT. Considering the good postoperative outcome, the biomarker levels may be considered "normal" after HT.

The knock-down of the expression of MdMLO19 reduces susceptibility to powdery mildew (Podosphaera leucotricha) in apple (Malus domestica).

Science.gov (United States)

Pessina, Stefano; Angeli, Dario; Martens, Stefan; Visser, Richard G F; Bai, Yuling; Salamini, Francesco; Velasco, Riccardo; Schouten, Henk J; Malnoy, Mickael

2016-10-01

Varieties resistant to powdery mildew (PM; caused by Podosphaera leucotricha) are a major component of sustainable apple production. Resistance can be achieved by knocking-out susceptibility S-genes to be singled out among members of the MLO (Mildew Locus O) gene family. Candidates are MLO S-genes of phylogenetic clade V up-regulated upon PM inoculation, such as MdMLO11 and 19 (clade V) and MdMLO18 (clade VII). We report the knock-down through RNA interference of MdMLO11 and 19, as well as the complementation of resistance with MdMLO18 in the Arabidopsis thaliana triple mlo mutant Atmlo2/6/12. The knock-down of MdMLO19 reduced PM disease severity by 75%, whereas the knock-down of MdMLO11, alone or in combination with MdMLO19, did not result in any reduction or additional reduction of susceptibility compared with MdMLO19 alone. The test in A. thaliana excluded a role for MdMLO18 in PM susceptibility. Cell wall appositions (papillae) were present in both PM-resistant and PM-susceptible plants, but were larger in resistant lines. No obvious negative phenotype was observed in plants with mlo genes knocked down. Apparently, MdMLO19 plays the pivotal role in apple PM susceptibility and its knock-down induces a very significant level of resistance. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

CRISPR/Cas-mediated knock-in via non-homologous end-joining in the crustacean Daphnia magna.

Science.gov (United States)

Kumagai, Hitoshi; Nakanishi, Takashi; Matsuura, Tomoaki; Kato, Yasuhiko; Watanabe, Hajime

2017-01-01

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas) is widely used for mediating the knock-in of foreign DNA into the genomes of various organisms. Here, we report a process of CRISPR/Cas-mediated knock-in via non-homologous end joining by the direct injection of Cas9/gRNA ribonucleoproteins (RNPs) in the crustacean Daphnia magna, which is a model organism for studies on toxicology, ecology, and evolution. First, we confirmed the cleavage activity of Cas9 RNPs comprising purified Cas9 proteins and gRNAs in D. magna. We used a gRNA that targets exon 10 of the eyeless gene. Cas9 proteins were incubated with the gRNAs and the resulting Cas9 RNPs were injected into D. magna eggs, which led to a typical phenotype of the eyeless mutant, i.e., eye deformity. The somatic and heritable mutagenesis efficiencies were up to 96% and 40%, respectively. Second, we tested the CRISPR/Cas-mediated knock-in of a plasmid by the injection of Cas9 RNPs. The donor DNA plasmid harboring the fluorescent reporter gene was designed to contain the gRNA recognition site. The co-injection of Cas9 RNPs together with the donor DNAs resulted in generation of one founder animal that produced fluorescent progenies. This transgenic Daphnia had donor DNA at the targeted genomic site, which suggested the concurrent cleavage of the injected plasmid DNA and genomic DNA. Owing to its simplicity and ease of experimental design, we suggest that the CRISPR/Cas-mediated knock-in method represents a promising tool for studying functional genomics in D. magna.

Influence of Compression Ratio on High Load Performance and Knock Behavior for Gasoline Port-Fuel Injection, Natural Gas Direct Injection and Blended Operation in a Spark Ignition Engine

Energy Technology Data Exchange (ETDEWEB)

Pamminger, Michael; Sevik, James; Scarcelli, Riccardo; Wallner, Thomas; Hall, Carrie

2017-03-28

Natural Gas (NG) is an alternative fuel which has attracted a lot of attention recently, in particular in the US due to shale gas availability. The higher hydrogen-to-carbon (H/C) ratio, compared to gasoline, allows for decreasing carbon dioxide emissions throughout the entire engine map. Furthermore, the high knock resistance of NG allows increasing the efficiency at high engine loads compared to fuels with lower knock resistance. NG direct injection (DI) allows for fuel to be added after intake valve closing (IVC) resulting in an increase in power density compared to an injection before IVC. Steady-state engine tests were performed on a single-cylinder research engine equipped with gasoline (E10) port-fuel injection (PFI) and NG DI to allow for in-cylinder blending of both fuels. Knock investigations were performed at two discrete compression ratios (CR), 10.5 and 12.5. Operating conditions span mid-load, wide-open-throttle and boosted conditions, depending on the knock response of the fuel blend. Blended operation was performed using E10 gasoline and NG. An additional gasoline type fuel (E85) with higher knock resistance than E10 was used as a high-octane reference fuel, since the octane rating of E10-NG fuel blends is unknown. Spark timing was varied at different loads under stoichiometric conditions in order to study the knock response as well as the effects on performance and efficiency. As anticipated, results suggest that the knock resistance can be increased significantly by increasing the NG amount. Comparing the engine operation with the least knock resistant fuel, E10 PFI, and the fuel blend with the highest knock resistance, 75% NG DI, shows an increase in indicated mean effective pressure of about 9 bar at CR 12.5. The usage of reference fuels with known knock characteristics allowed an assessment of knock characteristic of intermediate E10-NG blend levels. Mathematical correlations were developed allowing characterizing the occurrence of knocking

Role of blood ribosomal protein S19 in coagulum resorption: a study using Gln137Glu-ribosomal protein S19 gene knock-in mouse.

Science.gov (United States)

Chen, Jun; Fujino, Rika; Zhao, Rui; Semba, Umeko; Araki, Kimi; Yamamoto, Tetsuro

2014-11-01

Sera of human, guinea pig or mouse contain a strong monocyte chemoattractant capacity that is attributed to the ribosomal protein S19 (RP S19) oligomers generated during blood coagulation. In contrast, sera prepared from Gln137Glu-RP S19 gene knock-in mice contained negligible chemoattractant capacity. When coagula that had been pre-formed from the blood of both the wild type and knock-in mice were intraperitoneally inserted into host mice, after 3 days of recovery, the knock-in mouse coagula remained larger than the wild type mouse coagula. The wild type mouse coagula were covered by multiple macrophage layers at the surface and were infiltrated inside by macrophages. Knock-in mouse coagula exhibited less macrophage involvement. When coagula of knock-in mice and coagula of knock-in mice containing C5a/RP S19, an artificial substitute of the RP S19 oligomers, were intraperitoneally inserted as pairs, the C5a/RP S19 containing coagulum was more rapidly absorbed, concomitant with increased macrophage involvement. Finally, when the knock-in mouse and wild type mouse coagula pairs were inserted into mice in which macrophages had been depleted using clodronate liposome, the size difference of recovered coagula was reversed. These results indicate the importance of the RP S19 oligomer-induced macrophage recruitment in coagulum resorption. © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Analysis of Morphological Characteristics and Origins of Idiopathic Premature Ventricular Contractions Under a 12-Lead Electrocardiogram in Children with Structurally Normal Hearts.

Science.gov (United States)

Jiang, Jianbin; He, Yuee; Qiu, Huixian; Zhang, Yuanhai; Chu, Maoping; Li, Yuechun; Chen, Qi

2017-10-21

Up to 40% of healthy children have premature ventricular complexes or contractions (PVCs) detected with 24-hour Holter monitoring. We aimed to investigate the morphological characteristics and origins of idiopathic PVCs under a 12-lead electrocardiogram in children with structurally normal hearts. All asymptomatic monomorphic PVC patients with structurally normal hearts under 18 years of age were included in this retrospective study. Characteristics of PVCs in lead V 1 under a 12-lead electrocardiogram were classified as left bundle branch block (PVC-LBBB) or right bundle branch block (PVC-RBBB). According to limb leads, PVC-LBBB or PVC-RBBB was divided into: PVCs-LBBB type I; PVCs-LBBB type II; PVCs-RBBB type I; PVCs-RBBB type II; and PVCs-RBBB type III. Out of 178 PVC patients, 94 cases of PVCs-LBBB (PVCs-LBBB type I = 60; PVCs-LBBB type II = 34) and 84 cases of PVCs-RBBB (PVCs-RBBB type I = 3; PVCs-RBBB type II = 55; PVCs-RBBB type III = 26) were identified. The frequency of PVCs-LBBB type I increased with age and the frequency of PVCs-RBBB type II and III decreased with age. Among the children monitor tested, from 1 years old to 18 years old, PVCs originating from the left or right ventricular outflow tract gradually increased with age, while PVCs originating from the branch sources decreased with age.

The normal heart - Part I. The cardiac outline and chamber anatomy

International Nuclear Information System (INIS)

Walker, J.

1985-01-01

The heart is the most open and the most secret object in all radiology. Surrounded by alveolar air (its natural contrast) its outline dominates the chest X-ray. The lung vessels, responding to any change in function, are openly displayed, but within the heart borders the X-ray shadow is obscure and its parts invisible; moreover its vital purpose, movement, is not seen. This hollow muscular organ is conical, its apex points downwards, forwards and to the left at 60 0 to the midline. It is roughly 12 cm in length and weighs about 350 g. The main vessels enter and leave at the base posteriorly. Its apex is free within the serous cavity of the pericardium but its base is fixed by vessels and by the pericardial reflexions which surround them. The embryonic dorsal mesopericardium between arteries and veins breaks down to give the transverse sinus which frees the heart posteriorly, and the reflexions around the pulmonary veins form a blind sac, the oblique sinus, which opens to the left. All is enclosed by fibrous pericardium and occupies the anterior mediastinum at the level of the 6th-9th dorsal vertebrae from which it is separated by the oesophagus, aorta and spinal muscles. It rests on the central tendon of the diaphragm and laterally the right and left lungs envelop it over more than two thirds of its surface

Homologous Recombination-Independent Large Gene Cassette Knock-in in CHO Cells Using TALEN and MMEJ-Directed Donor Plasmids

Directory of Open Access Journals (Sweden)

Tetsushi Sakuma

2015-10-01

Full Text Available Gene knock-in techniques have rapidly evolved in recent years, along with the development and maturation of genome editing technology using programmable nucleases. We recently reported a novel strategy for microhomology-mediated end-joining-dependent integration of donor DNA by using TALEN or CRISPR/Cas9 and optimized targeting vectors, named PITCh (Precise Integration into Target Chromosome vectors. Here we describe TALEN and PITCh vector-mediated integration of long gene cassettes, including a single-chain Fv-Fc (scFv-Fc gene, in Chinese hamster ovary (CHO cells, with comparison of targeting and cloning efficiency among several donor design and culture conditions. We achieved 9.6-kb whole plasmid integration and 7.6-kb backbone-free integration into a defined genomic locus in CHO cells. Furthermore, we confirmed the reasonable productivity of recombinant scFv-Fc protein of the knock-in cells. Using our protocol, the knock-in cell clones could be obtained by a single transfection and a single limiting dilution using a 96-well plate, without constructing targeting vectors containing long homology arms. Thus, the study described herein provides a highly practical strategy for gene knock-in of large DNA in CHO cells, which accelerates high-throughput generation of cell lines stably producing any desired biopharmaceuticals, including huge antibody proteins.

Intracellular generation of single-strand template increases the knock-in efficiency by combining CRISPR/Cas9 with AAV.

Science.gov (United States)

Xiao, Qing; Min, Taishan; Ma, Shuangping; Hu, Lingna; Chen, Hongyan; Lu, Daru

2018-04-18

Targeted integration of transgenes facilitates functional genomic research and holds prospect for gene therapy. The established microhomology-mediated end-joining (MMEJ)-based strategy leads to the precise gene knock-in with easily constructed donor, yet the limited efficiency remains to be further improved. Here, we show that single-strand DNA (ssDNA) donor contributes to efficient increase of knock-in efficiency and establishes a method to achieve the intracellular linearization of long ssDNA donor. We identified that the CRISPR/Cas9 system is responsible for breaking double-strand DNA (dsDNA) of palindromic structure in inverted terminal repeats (ITRs) region of recombinant adeno-associated virus (AAV), leading to the inhibition of viral second-strand DNA synthesis. Combing Cas9 plasmids targeting genome and ITR with AAV donor delivery, the precise knock-in of gene cassette was achieved, with 13-14% of the donor insertion events being mediated by MMEJ in HEK 293T cells. This study describes a novel method to integrate large single-strand transgene cassettes into the genomes, increasing knock-in efficiency by 13.6-19.5-fold relative to conventional AAV-mediated method. It also provides a comprehensive solution to the challenges of complicated production and difficult delivery with large exogenous fragments.

Homologous Recombination-Independent Large Gene Cassette Knock-in in CHO Cells Using TALEN and MMEJ-Directed Donor Plasmids.

Science.gov (United States)

Sakuma, Tetsushi; Takenaga, Mitsumasa; Kawabe, Yoshinori; Nakamura, Takahiro; Kamihira, Masamichi; Yamamoto, Takashi

2015-10-09

Gene knock-in techniques have rapidly evolved in recent years, along with the development and maturation of genome editing technology using programmable nucleases. We recently reported a novel strategy for microhomology-mediated end-joining-dependent integration of donor DNA by using TALEN or CRISPR/Cas9 and optimized targeting vectors, named PITCh (Precise Integration into Target Chromosome) vectors. Here we describe TALEN and PITCh vector-mediated integration of long gene cassettes, including a single-chain Fv-Fc (scFv-Fc) gene, in Chinese hamster ovary (CHO) cells, with comparison of targeting and cloning efficiency among several donor design and culture conditions. We achieved 9.6-kb whole plasmid integration and 7.6-kb backbone-free integration into a defined genomic locus in CHO cells. Furthermore, we confirmed the reasonable productivity of recombinant scFv-Fc protein of the knock-in cells. Using our protocol, the knock-in cell clones could be obtained by a single transfection and a single limiting dilution using a 96-well plate, without constructing targeting vectors containing long homology arms. Thus, the study described herein provides a highly practical strategy for gene knock-in of large DNA in CHO cells, which accelerates high-throughput generation of cell lines stably producing any desired biopharmaceuticals, including huge antibody proteins.

[Analysis of the heart sound with arrhythmia based on nonlinear chaos theory].

Science.gov (United States)

Ding, Xiaorong; Guo, Xingming; Zhong, Lisha; Xiao, Shouzhong

2012-10-01

In this paper, a new method based on the nonlinear chaos theory was proposed to study the arrhythmia with the combination of the correlation dimension and largest Lyapunov exponent, through computing and analyzing these two parameters of 30 cases normal heart sound and 30 cases with arrhythmia. The results showed that the two parameters of the heart sounds with arrhythmia were higher than those with the normal, and there was significant difference between these two kinds of heart sounds. That is probably due to the irregularity of the arrhythmia which causes the decrease of predictability, and it's more complex than the normal heart sound. Therefore, the correlation dimension and the largest Lyapunov exponent can be used to analyze the arrhythmia and for its feature extraction.

Relevant feature set estimation with a knock-out strategy and random forests

DEFF Research Database (Denmark)

Ganz, Melanie; Greve, Douglas N; Fischl, Bruce

2015-01-01

unintuitive and difficult to determine. In this article, we propose a novel MVPA method for group analysis of high-dimensional data that overcomes the drawbacks of the current techniques. Our approach explicitly aims to identify all relevant variations using a "knock-out" strategy and the Random Forest...

Terpineol as a novel octane booster for extending the knock limit of gasoline

KAUST Repository

Vallinayagam, R.

2016-09-16

Improving the octane number of gasoline offers the potential of improved engine combustion, as it permits spark timing advancement without engine knock. This study proposes the use of terpineol as an octane booster for gasoline in a spark ignited (SI) engine. Terpineol is a bio-derived oxygenated fuel obtained from pine tree resin, and has the advantage of higher calorific value than ethanol. The ignition delay time (IDT) of terpineol was first investigated in an ignition quality tester (IQT). The IQT results demonstrated a long ignition delay of 24.7 ms for terpineol and an estimated research octane number (RON) of 104, which was higher than commercial European (Euro V) gasoline. The octane boosting potential of terpineol was further investigated by blending it with a non-oxygenated gasoline (FACE F), which has a RON (94) lower than Euro V gasoline (RON = 97). The operation of a gasoline direct injection (GDI) SI engine fueled with terpineol-blended FACE F gasoline enabled spark timing advancement and improved engine combustion. The knock intensity of FACE F + 30% terpineol was lower than FACE F gasoline at both maximum brake torque (MBT) and knock limited spark advance (KLSA) operating points. Increasing proportions of terpineol in the blend caused peak heat release rate, in-cylinder pressure, CA50, and combustion duration to be closer to those of Euro V gasoline. Furthermore, FACE F + 30% terpineol displayed improved combustion characteristics when compared to Euro V gasoline. © 2016

Patient experiences of recovery after heart valve replacement: suffering weakness, struggling to resume normality

DEFF Research Database (Denmark)

Kikkenborg Berg, Selina; Zwisler, Ann-Dorthe; Pedersen, Birthe D.

2013-01-01

Heart valve disease is becoming a public health problem due to increasing life expectancy and new treatment methods. Patients are at risk of developing depression, anxiety or post-traumatic stress disorder after heart valve surgery. To better plan proper care, describing and understanding patients...

Detection and prognostic impact of renal dysfunction in patients with chronic heart failure and normal serum creatinine.

Science.gov (United States)

Scrutinio, Domenico; Passantino, Andrea; Lagioia, Rocco; Santoro, Daniela; Cacciapaglia, Erasmo

2011-03-03

Accurate identification of renal dysfunction (RD) is crucial to risk stratification in chronic heart failure (CHF). Patients with CHF are at special risk of having RD despite normal serum creatinine (SCr), owing to a decreased Cr generation. At low levels of SCr, the equations estimating renal function are less accurate. This study was aimed to assess and compare the prognostic value of formulas estimating renal function in CHF patients with normal SCr. We studied 462 patients with systolic CHF and normal SCr. Creatinine clearance was estimated by the Cockcroft-Gault (eCrCl) and glomerular filtration rate by the 4-variable MDRD equation (eGFR); eCrCl normalized for body-surface area (eCrCl(BSA)) was calculated. The primary outcome was all-cause mortality at 2 years. Seventy five patients died. At multivariate Cox regression analysis, only eCrCl(BSA) was significantly associated with mortality (p = 0.006); eGFR (p = 0.24), eCrCl (p = 0.09) and BUN (p = 0.14) were not statistically significant predictors. The patients in the lowest eCrCl(BSA) quartile had an adjusted 2.1-fold (CI: 1.06-4.1) increased risk of mortality, compared with those in the referent quartile. Two-year survival was 70.4% in the lowest eCrCl(BSA) quartile and 89.7% in the referent quartile. Other independent predictors of mortality were ischemic etiology (RR: 2.16 [CI: 1.3-3.5], p = 0.0017), NYHA III/IV class (RR: 2.45 [CI: 1.51-3.97], p = 0.0003), LVEF high-risk subgroup and can more accurately be identified by the CG formula corrected for BSA than the MDRD. Copyright © 2009 Elsevier B.V. All rights reserved.

Heart Transplant in Patients with Predominantly Rheumatic Valvular Heart Disease.

Science.gov (United States)

Rosa, Vitor E E; Lopes, Antonio S S A; Accorsi, Tarso A D; Fernandes, Joao Ricardo C; Spina, Guilherme S; Sampaio, Roney O; Bacal, Fernando; Tarasoutchi, Flavio

2015-09-01

International records indicate that only 2.6% of patients with heart transplants have valvular heart disease. The study aim was to evaluate the epidemiological and clinical profile of patients with valvular heart disease undergoing heart transplantation. Between 1985 and 2013, a total of 569 heart transplants was performed at the authors' institution. Twenty patients (13 men, seven women; mean age 39.5 +/- 15.2 years) underwent heart transplant due to structural (primary) valvular disease. Analyses were made of the patients' clinical profile, laboratory data, echocardiographic and histopathological data, and mortality and rejection. Of the patients, 18 (90%) had a rheumatic etiology, with 85% having undergone previous valve surgery (45% had one or more operations), and 95% with a normal functioning valve prosthesis at the time of transplantation. Atrial fibrillation was present in seven patients (35%), while nine (45%) were in NYHA functional class IV and eight (40%) in class III. The indication for cardiac transplantation was refractory heart failure in seven patients (35%) and persistent NYHA class III/IV in ten (50%). The mean left ventricular ejection fraction (LVEF) was 26.6 +/- 7.9%. The one-year mortality was 20%. Histological examination of the recipients' hearts showed five (27.7%) to have reactivated rheumatic myocarditis without prior diagnosis at the time of transplantation. Univariate analysis showed that age, gender, LVEF, rheumatic activity and rejection were not associated with mortality at one year. Among the present patient cohort, rheumatic heart disease was the leading cause of heart transplantation, and a significant proportion of these patients had reactivated myocarditis diagnosed in the histological analyses. Thus, it appears valid to investigate the existence of rheumatic activity, especially in valvular cardiomyopathy with severe systolic dysfunction before transplantation.

Normal Values for Heart Electrophysiology Parameters of Healthy Swine Determined on Electrophysiology Study.

Science.gov (United States)

Noszczyk-Nowak, Agnieszka; Cepiel, Alicja; Janiszewski, Adrian; Pasławski, Robert; Gajek, Jacek; Pasławska, Urszula; Nicpoń, Józef

2016-01-01

Swine are a well-recognized animal model for human cardiovascular diseases. Despite the widespread use of porcine model in experimental electrophysiology, still no reference values for intracardiac electrical activity and conduction parameters determined during an invasive electrophysiology study (EPS) have been developed in this species thus far. The aim of the study was to develop a set of normal values for intracardiac electrical activity and conduction parameters determined during an invasive EPS of swine. The study included 36 healthy domestic swine (24-40 kg body weight). EPS was performed under a general anesthesia with midazolam, propofol and isoflurane. The reference values for intracardiac electrical activity and conduction parameters were calculated as arithmetic means ± 2 standard deviations. The reference values were determined for AH, HV and PA intervals, interatrial conduction time at its own and imposed rhythm, sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), anterograde and retrograde Wenckebach points, atrial, atrioventricular node and ventricular refractory periods. No significant correlations were found between body weight and heart rate of the examined pigs and their electrophysiological parameters. The hereby presented reference values can be helpful in comparing the results of various studies, as well as in more accurately estimating the values of electrophysiological parameters that can be expected in a given experiment.

Terpineol as a novel octane booster for extending the knock limit of gasoline

KAUST Repository

Vallinayagam, R.; Vedharaj, S.; Naser, Nimal; Roberts, William L.; Dibble, Robert W.; Sarathy, Mani

2016-01-01

Improving the octane number of gasoline offers the potential of improved engine combustion, as it permits spark timing advancement without engine knock. This study proposes the use of terpineol as an octane booster for gasoline in a spark ignited

Diabetes, Dyslipidemia, and Heart Protection

Science.gov (United States)

Fact Sheet Diabetes, Dyslipidemia, and Heart Protection What is dyslipidemia? Cholesterol and triglycerides, known as lipids, are fatty substances that the body normally produces. Dyslipidemia means that lipid levels ...

Generation and analysis of knock-in mice carrying pseudohypoaldosteronism type II-causing mutations in the cullin 3 gene.

Science.gov (United States)

Araki, Yuya; Rai, Tatemitsu; Sohara, Eisei; Mori, Takayasu; Inoue, Yuichi; Isobe, Kiyoshi; Kikuchi, Eriko; Ohta, Akihito; Sasaki, Sei; Uchida, Shinichi

2015-10-21

Pseudohypoaldosteronism type II (PHAII) is a hereditary hypertensive disease caused by mutations in four different genes: with-no-lysine kinases (WNK) 1 and 4, Kelch-like family member 3 (KLHL3), and cullin 3 (Cul3). Cul3 and KLHL3 form an E3 ligase complex that ubiquitinates and reduces the expression level of WNK4. PHAII-causing mutations in WNK4 and KLHL3 impair WNK4 ubiquitination. However, the molecular pathogenesis of PHAII caused by Cul3 mutations is unclear. In cultured cells and human leukocytes, PHAII-causing Cul3 mutations result in the skipping of exon 9, producing mutant Cul3 protein lacking 57 amino acids. However, whether this phenomenon occurs in the kidneys and is responsible for the pathogenesis of PHAII in vivo is unknown. We generated knock-in mice carrying a mutation in the C-terminus of intron 8 of Cul3, c.1207-1G>A, which corresponds to a PHAII-causing mutation in the human Cul3 gene. Heterozygous Cul3(G(-1)A/+) knock-in mice did not exhibit PHAII phenotypes, and the skipping of exon 9 was not evident in their kidneys. However, the level of Cul3 mRNA expression in the kidneys of heterozygous knock-in mice was approximately half that of wild-type mice. Furthermore, homozygous knock-in mice were nonviable. It suggested that the mutant allele behaved like a knockout allele and did not produce Cul3 mRNA lacking exon 9. A reduction in Cul3 expression alone was not sufficient to develop PHAII in the knock-in mice. Our findings highlighted the pathogenic role of mutant Cul3 protein and provided insight to explain why PHAII-causing mutations in Cul3 cause kidney-predominant PHAII phenotypes. © 2015. Published by The Company of Biologists Ltd.

Timing of left heart base descent in dogs with dilated cardiomyopathy and normal dogs.

Science.gov (United States)

Simpson, Kerry E; Devine, Bryan C; Woolley, Richard; Corcoran, Brendan M; French, Anne T

2008-01-01

The identification and assessment of myocardial failure in canine idiopathic dilated cardiomyopathy (DCM) is achieved using a variety of two-dimensional and Doppler echocardiographic techniques. More recently, the availability of tissue Doppler imaging (TDI) has raised the potential for development of new ways of more accurately identifying a disease phenotype. Nevertheless, TDI has not been universally adapted to veterinary clinical cardiology primarily because of the lack of information on its utility in diagnosis. We assessed the application of timing of left heart base descent using TDI in the identification of differences between DCM and normal dogs. The times from the onset of the QRS complex on a simultaneously recorded electrocardiograph to the onset (Q--S'), peak (Q--peak S'), and end (Q--end S') of the systolic velocity peak were measured in the interventricular septum (IVS) and the left ventricular free wall. The duration of S' was also calculated. The Q--S' (FW), Q--end S' (FW), and duration S' (FW) were correlated with ejection fraction in the diseased group (P canine DCM and identifies new TDI parameters that can be added to the range of Doppler and echocardiographic parameters used for detecting myocardial failure in the dog.

Echocardiographic Evaluation of Hemodynamic Changes in Left-Sided Heart Valves in Pregnant Women With Valvular Heart Disease.

Science.gov (United States)

Samiei, Niloufar; Amirsardari, Mandana; Rezaei, Yousef; Parsaee, Mozhgan; Kashfi, Fahimeh; Hantoosh Zadeh, Sedigheh; Beikmohamadi, Somayeh; Fouladi, Masoumeh; Hosseini, Saeid; Peighambari, Mohammad Mehdi; Mohebbi, Ahmad

2016-10-01

Physiologic changes during pregnancy can deteriorate or improve patients' hemodynamic status in the setting of valvular heart disease. There are sparse data regarding the effect of pregnancy on valve hemodynamics in normal pregnant women with known valvular heart disease. In a prospective study from July 2014 to January 2016, a total of 52 normal pregnant women who had mitral stenosis, aortic stenosis, or a history of mitral valve or aortic valve replacements were assessed. All patients underwent echocardiographic examinations and hemodynamic parameters were measured for both the mitral valve and aortic valve at first, second, and third trimesters. The parameters included mean gradient, peak gradient, mean gradient/heart rate, peak gradient/heart rate, pressure halftime, dimensionless velocity index, and valve area. Although most hemodynamic parameters (i.e., mean gradient, peak gradient, mean gradient/heart rate, and peak gradient/heart rate) increased approximately 50% from first to second trimester and first to third trimester (p 0.05). The ratio of changes between trimesters for valve area and dimensionless velocity index were comparable. No clinical decompensations were observed except for 3 and 7 cases of deterioration to functional class II at second and third trimesters, respectively. In conclusion, during a full-term and uncomplicated pregnancy, mitral and aortic valve gradients increase without significant changes in valve area that are more marked between the second and first trimester than between the third and second trimester. Copyright © 2016 Elsevier Inc. All rights reserved.

Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts

NARCIS (Netherlands)

Vermeulen, J. T.; McGuire, M. A.; Opthof, T.; Coronel, R.; de Bakker, J. M.; Klöpping, C.; Janse, M. J.

1994-01-01

The aim of the study was to assess the occurrence of triggered activity and automaticity in ventricular trabeculae from failing human hearts and normal and failing rabbit hearts during exposure to a normal and altered extracellular environment. Ventricular trabeculae were harvested from failing

Effect of Timing and Location of Hotspot on Super Knock during Pre-ignition

KAUST Repository

Jaasim, Mohammed; Hernandez Perez, Francisco; Vedharaj, S.; Vallinayagam, R.; Dibble, Robert W.; Im, Hong G.

2017-01-01

Pre-ignition in SI engine is a critical issue that needs addressing as it may lead to super knock event. It is widely accepted that pre-ignition event emanates from hot spot(s) that can be anywhere inside the combustion chamber. The location

Infective endocarditis involving an apparently structurally normal valve: new epidemiological trend?

Science.gov (United States)

Song, Jae-Kwan

2015-07-01

Infective endocarditis (IE) has been increasingly diagnosed in patients without previously detected predisposing heart disease, but its clinical features have yet to be fully determined. A recent single-center study including echocardiographic images and surgical findings investigated the incidence of undiagnosed, clinically silent valvular or congenital heart diseases and healthcare-associated infective endocarditis (HAIE). The study confirmed that a large proportion of patients with IE have no previous history of heart disease. Analysis of underlying disease in these patients showed that undetected mitral valve prolapse was the most common disease, followed by an apparently structurally normal valve. The patients who developed IE of apparently structurally normal valves had different clinical characteristics and worse outcomes. IE involving a structurally normal valve was associated with both nosocomial and non-nosocomial HAIE, whereas community-acquired IE was more frequent than HAIE. The pathophysiologic mechanism involving the development of non-HAIE or community-acquired IE due to predominantly staphylococcal infection in an apparently structurally normal valve is not yet clearly understood. Structurally normal valves are not necessarily free of regurgitation or abnormal turbulence and, given the dynamic nature and fluctuating hemodynamic effects of conditions such as poorly controlled hypertension, end-stage renal disease, and sleep apnea, further investigation is necessary to evaluate the potential role of these diseases in the development of IE. An apparently normal-looking valve is associated with IE development in patients without previously recognized predisposing heart disease, warranting repartition of at-risk groups to achieve better clinical outcomes.

A novel luciferase knock-in reporter system for studying transcriptional regulation of the human Sox2 gene.

Science.gov (United States)

Xiao, Dan; Zhang, Weifeng; Li, Yan; Liu, Kuan; Zhao, Junli; Sun, Xiaohong; Shan, Linlin; Mao, Qinwen; Xia, Haibin

2016-02-10

Sox2 is an important transcriptional factor that has multiple functions in stem cell maintenance and tumorigenesis. To investigate the transcriptional regulation of the Sox2 gene, a luciferase knock-in reporter system was established in HEK293 cells by placing the luciferase gene in the genome under the control of the Sox2 gene promoter using a transcription activator-like effector nuclease (TALEN)-mediated genome editing technique. PCR and Southern blot results confirmed the site-specific integration of a single copy of the exogenous luciferase gene into the genome. To prove the reliability and sensitivity of this novel luciferase knock-in system, a CRISPR/Cas transcription activation system for the Sox2 gene was constructed and applied to the knock-in system. The results indicated that luciferase activity was directly correlated with the activity of the Sox2 endogenous promoter. This novel system will be a useful tool to study the transcriptional regulation of Sox2, and has great potential in medical and industrial applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Vapb/Amyotrophic lateral sclerosis 8 knock-in mice display slowly progressive motor behavior defects accompanying ER stress and autophagic response.

Science.gov (United States)

Larroquette, Frédérique; Seto, Lesley; Gaub, Perrine L; Kamal, Brishna; Wallis, Deeann; Larivière, Roxanne; Vallée, Joanne; Robitaille, Richard; Tsuda, Hiroshi

2015-11-15

Missense mutations (P56S) in Vapb are associated with autosomal dominant motor neuron diseases: amyotrophic lateral sclerosis and lower motor neuron disease. Although transgenic mice overexpressing the mutant vesicle-associated membrane protein-associated protein B (VAPB) protein with neuron-specific promoters have provided some insight into the toxic properties of the mutant proteins, their role in pathogenesis remains unclear. To identify pathological defects in animals expressing the P56S mutant VAPB protein at physiological levels in the appropriate tissues, we have generated Vapb knock-in mice replacing wild-type Vapb gene with P56S mutant Vapb gene and analyzed the resulting pathological phenotypes. Heterozygous P56S Vapb knock-in mice show mild age-dependent defects in motor behaviors as characteristic features of the disease. The homozygous P56S Vapb knock-in mice show more severe defects compared with heterozygous mice reflecting the dominant and dose-dependent effects of P56S mutation. Significantly, the knock-in mice demonstrate accumulation of P56S VAPB protein and ubiquitinated proteins in cytoplasmic inclusions, selectively in motor neurons. The mutant mice demonstrate induction of ER stress and autophagic response in motor neurons before obvious onset of behavioral defects, suggesting that these cellular biological defects might contribute to the initiation of the disease. The P56S Vapb knock-in mice could be a valuable tool to gain a better understanding of the mechanisms by which the disease arises. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Knockdown of αII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair

OpenAIRE

McMahon, Laura W.; Zhang, Pan; Sridharan, Deepa M.; Lefferts, Joel A.; Lambert, Muriel W.

2009-01-01

Nonerythroid α-spectrin (αIISp) is a structural protein involved in repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), which are defective in ability to repair cross-links. In order to further demonstrate the importance of the role that αIISp plays in normal human cells and in the repair defect in FA, αIISp was knocked down in normal cells using siRNA. Depletion of αIISp in normal cells by siRNA resulted in chromosomal instability and cellu...

CRISPR/Cas9-Mediated Zebrafish Knock-in as a Novel Strategy to Study Midbrain-Hindbrain Boundary Development.

Science.gov (United States)

Kesavan, Gokul; Chekuru, Avinash; Machate, Anja; Brand, Michael

2017-01-01

The midbrain-hindbrain boundary (MHB) acts as an organizer and controls the fate of neighboring cells to develop into either mesencephalic (midbrain) or metencephalic (hindbrain) cells by secreting signaling molecules like Wnt1 and Fgf8. The zebrafish is an excellent vertebrate model for studying MHB development due to the ease of gene manipulation and the possibility of following cellular dynamics and morphogenetic processes using live imaging. Currently, only very few reporter and/or Cre-driver lines are available to study gene expression at the MHB, hampering the understanding of MHB development, and traditional transgenic technologies using promoter/enhancer fragments or bacterial artificial chromosome (BAC)-mediated transgenesis often do not faithfully recapitulate endogenous expression patterns. In contrast, CRISPR/Cas9-mediated genome editing technology now provides a great opportunity to efficiently knock-in or knock-out genes. We have generated four CRISPR/Cas9-based knock-in fluorescent reporter lines for two crucial genes involved in MHB development, namely otx2 and pax2a . The coding sequences of the reporters were knocked-in upstream of the corresponding ATG and are, thus, under the control of the endogenous promoter/enhancer elements. Interestingly, this strategy does not disturb endogenous gene expression. Using the fast maturing fluorescent protein reporter, Venus, enabled us to follow MHB development using cell tracking and live imaging. In addition, we show that these reporter lines label various neuronal and glial cell types in the adult zebrafish brain, making them highly suitable for investigating embryonic and adult midbrain, hindbrain, and MHB development.

A Physical Heart Failure Simulation System Utilizing the Total Artificial Heart and Modified Donovan Mock Circulation.

Science.gov (United States)

Crosby, Jessica R; DeCook, Katrina J; Tran, Phat L; Betterton, Edward; Smith, Richard G; Larson, Douglas F; Khalpey, Zain I; Burkhoff, Daniel; Slepian, Marvin J

2017-07-01

With the growth and diversity of mechanical circulatory support (MCS) systems entering clinical use, a need exists for a robust mock circulation system capable of reliably emulating and reproducing physiologic as well as pathophysiologic states for use in MCS training and inter-device comparison. We report on the development of such a platform utilizing the SynCardia Total Artificial Heart and a modified Donovan Mock Circulation System, capable of being driven at normal and reduced output. With this platform, clinically relevant heart failure hemodynamics could be reliably reproduced as evidenced by elevated left atrial pressure (+112%), reduced aortic flow (-12.6%), blunted Starling-like behavior, and increased afterload sensitivity when compared with normal function. Similarly, pressure-volume relationships demonstrated enhanced sensitivity to afterload and decreased Starling-like behavior in the heart failure model. Lastly, the platform was configured to allow the easy addition of a left ventricular assist device (HeartMate II at 9600 RPM), which upon insertion resulted in improvement of hemodynamics. The present configuration has the potential to serve as a viable system for training and research, aimed at fostering safe and effective MCS device use. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Physicochemical effects of varying fuel composition on knock characteristics of natural gas mixtures

NARCIS (Netherlands)

Gersen, Sander; van Essen, Martijn; van Dijk, Gerco; Levinsky, Howard

2014-01-01

The physicochemical origins of how changes in fuel composition affect autoignition of the end gas, leading to engine knock, are analyzed for a natural gas engine. Experiments in a lean-burn, high-speed medium-BMEP gas engine are performed using a reference natural gas with systematically varied

Correlates of lung/heart ratio of thallium-201 in coronary artery disease

International Nuclear Information System (INIS)

Homma, S.; Kaul, S.; Boucher, C.A.

1987-01-01

We studied 306 patients with chest pain (262 with coronary artery disease and 44 with no coronary artery disease) to determine which of 23 clinical, exercise, thallium, and angiographic variables best discriminate between patients with increased lung/heart ratios of thallium versus those with normal ratios. Normal lung/heart ratio values were defined using an additional 45 subjects with less than 1% probability of coronary artery disease. The number of diseased vessels was the best discriminator between patients with increased ratios versus those with normal ratios. Double product at peak exercise, number of segments with abnormal wall motion, patient gender, and duration of exercise were also significant discriminators. Using discriminant function analysis these variables could correctly identify 81% of cases with increased lung/heart ratios and 72% of cases with normal ratios. These results indicate that an increased lung/heart ratio of thallium reflects exercise-induced left ventricular dysfunction and affords a better understanding of why this thallium parameter is a powerful prognostic indicator in patients with chest pain

Protein phosphatase 2ACα gene knock-out results in cortical atrophy through activating hippo cascade in neuronal progenitor cells.

Science.gov (United States)

Liu, Bo; Sun, Li-Hua; Huang, Yan-Fei; Guo, Li-Jun; Luo, Li-Shu

2018-02-01

Protein phosphatase 2ACα (PP2ACα), a vital member of the protein phosphatase family, has been studied primarily as a regulator for the development, growth and protein synthesis of a lot of cell types. Dysfunction of PP2ACα protein results in neurodegenerative disease; however, this finding has not been directly confirmed in the mouse model with PP2ACα gene knock-out. Therefore, in this study presented here, we generated the PP2ACα gene knock-out mouse model by the Cre-loxP targeting gene system, with the purpose to directly observe the regulatory role of PP2ACα gene in the development of mouse's cerebral cortex. We observe that knocking-out PP2ACα gene in the central nervous system (CNS) results in cortical neuronal shrinkage, synaptic plasticity impairments, and learning/memory deficits. Further study reveals that PP2ACα gene knock-out initiates Hippo cascade in cortical neuroprogenitor cells (NPCs), which blocks YAP translocation into the nuclei of NPCs. Notably, p73, directly targeted by Hippo cascade, can bind to the promoter of glutaminase2 (GLS2) that plays a dominant role in the enzymatic regulation of glutamate/glutamine cycle. Finally, we find that PP2ACα gene knock-out inhibits the glutamine synthesis through up-regulating the activity of phosphorylated-p73 in cortical NPCs. Taken together, it concludes that PP2ACα critically supports cortical neuronal growth and cognitive function via regulating the signaling transduction of Hippo-p73 cascade. And PP2ACα indirectly modulates the glutamine synthesis of cortical NPCs through targeting p73 that plays a direct transcriptional regulatory role in the gene expression of GLS2. Copyright © 2017 Elsevier Ltd. All rights reserved.

On the knock-out mechanism for the 12C(P,α)9B reaction

International Nuclear Information System (INIS)

Hassan, M.Y.M.; Ismail, E.H.; Rabie, A.

1978-01-01

The mechanism of the reaction 12 C(P,α) 9 B is studied using zero range distorted wave Born approximation. The knock out mechanism is assumed to represent this reaction both in the forward and backward angles. (orig.) [de

Liver failure in total artificial heart therapy.

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Dimitriou, Alexandros Merkourios; Dapunt, Otto; Knez, Igor; Wasler, Andrae; Oberwalder, Peter; Koerfer, Reiner; Tenderich, Gero; Spiliopoulos, Sotirios

2016-07-01

Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality.

Chest radiographic findings and complications of the temporary implantation of the Jarvik-7 artificial heart while patients await orthotopic heart transplantation

International Nuclear Information System (INIS)

Sadler, L.; Fuhrman, C.; Hardesty, R.; Griffith, B.

1987-01-01

At the University of Pittsburgh, the authors have had 15 patients in whom Jarvik-7 hearts were implanted as a temporary measure while the patients awaited suitable donors for cardiac transplantation. The paper presents a brief description of the Jarvik-7 artificial heart, factors affecting patient selection, and the radiographic appearance of a normally functioning Jarvik-7 heart, and reviews the chest radiographic complications seen in this patient group, along with eventual patient outcome

Study Heart Rate by Tools from Complex Networks

International Nuclear Information System (INIS)

Makowiec, D.; Wdowczyk-Szulc, J.; Zarczynska-Buchowiecka, M.; Gruchala, M.; Rynkiewicz, A.

2011-01-01

Heart rate measured as beat-to-beat time intervals varies in time. It is believed that time intervals between subsequent normal heart contractions carry information about the regulatory system of the heart. How to quantify such signals is not clear and because of that heart rate variability is still apart from the clinic routine. In the following, we propose a method for representing a heart rate signal as a directed network. Then we study the signal properties by complex network tools. The signals to study were collected from patients recovering after the heart transplantation. The aim is to classify the progress of adapting of the new heart - graft. Moreover, it is expected that the method allows for visual classification. Our investigations are preliminary, however the obtained results are promising. (authors)

Metabolic variations of fatty acid in isolated rat heart reperfused after a transient global ischemia

International Nuclear Information System (INIS)

Huang Gang; Michel Comet; Zhao Huiyang; Zhu Cuiying; Yuan Jimin

1998-01-01

Purpose: The fatty acid metabolism and the effect of glucose on it were studied in isolated and reperfused rat heat. Methods: 32 isolated working rat hearts were perfused in Langengdorff device with modified Krebs and were divided into normal and ischemia-reperfused group. Each group was also classified into two subgroups, modified krebs with or without glucose subgroup. 131 I-HA was injected into aorta of isolated working rat heart and then the radio-residue curves were acquired. Results: When the isolated rat hearts were perfused with krebs plus glucose, the catabolism of fatty acid was significantly decreased in normal group, but a remarkable increase of fatty acid catabolism was found in ischemia-reperfused group. While the isolated rat hearts were perfused with krebs without glucose, the catabolism of fatty acid in ischemia-reperfused isolated rat hearts were perfused with krebs without glucose, the catabolism of fatty acid in ischemia-reperfused isolated rat heart was less than that in normal group. Conclusions: Transient ischemia damages the catabolism of myocardial fatty acid in mitochondria in some degree. In normal isolated working rat heart, the principal energy source is glucose. However, the major energy source is switched to catabolism of fatty acid in ischemia-reperfused isolated rat heart. This phenomenon may be related to compensative increase of fatty acid catabolism for replenishing the loss of energy during ischemia

Variation in heart rate influences the assessment of transient ischemic dilation in myocardial perfusion scintigraphy

International Nuclear Information System (INIS)

Leslie, William D; Levin, Daniel P; Demeter, Sandor J

2007-01-01

Transient arrhythmias can affect transient ischemic dilation (TID) ratios. This study was initiated to evaluate the frequency and effect of normal heart rate change on TID measures in routine clinical practice. Consecutive patients undergoing stress/rest sestamibi gated myocardial perfusion scintigraphy were studied (N = 407). Heart rate at the time of stress and rest imaging were recorded. TID ratios were analyzed in relation to absolute change in heart rate (stress minus rest) for subjects with normal perfusion and systolic function (Group 1, N = 169) and those with abnormalities in perfusion and/or function (Group 2, N = 238). In Group 1, mean TID ratio was inversely correlated with the change in heart rate (r = -0.47, P < 0.0001). For every increase of 10 BPM in heart rate change, the TID ratio decreased by approximately 0.06 (95% confidence interval 0.04–0.07). In Group 2, multiple linear regression demonstrated that the change in heart rate (beta = -0.25, P < 0.0001) and the summed difference score (beta = 0.36, P < 0.0001) were independent predictors of the TID ratio. Normal variation in heart rate between the stress and rest components of myocardial perfusion scans is common and can influence TID ratios in patients with normal and abnormal cardiac scans

4D flow MRI assessment of right atrial flow patterns in the normal heart - influence of caval vein arrangement and implications for the patent foramen ovale.

Directory of Open Access Journals (Sweden)

Jehill D Parikh

Full Text Available To investigate atrial flow patterns in the normal adult heart, to explore whether caval vein arrangement and patency of the foramen ovale (PFO may be associated with flow pattern.Time-resolved, three-dimensional velocity encoded magnetic resonance imaging (4D flow was employed to assess atrial flow patterns in thirteen healthy subjects (6 male, 40 years, range 25-50 and thirteen subjects (6 male, 40 years, range 21-50 with cryptogenic stroke and patent foramen ovale (CS-PFO. Right atrial flow was defined as vortical, helico-vortical, helical and multiple vortices. Time-averaged and peak systolic and diastolic flows in the caval and pulmonary veins and their anatomical arrangement were compared.A spectrum of right atrial flow was observed across the four defined categories. The right atrial flow patterns were strongly associated with the relative position of the caval veins. Right atrial flow patterns other than vortical were more common (p = 0.015 and the separation between the superior and inferior vena cava greater (10±5mm versus 3±3mm, p = 0.002 in the CS-PFO group. In the left atrium all subjects except one had counter-clockwise vortical flow. Vortex size varied and was associated with left lower pulmonary vein flow (systolic r = 0.61, p = 0.001, diastolic r = 0.63 p = 0.002. A diastolic vortex was less common and time-averaged left atrial velocity was greater in the CS-PFO group (17±2cm/sec versus 15±1, p = 0.048. One CS-PFO subject demonstrated vortical retrograde flow in the descending aortic arch; all other subjects had laminar descending aortic flow.Right atrial flow patterns in the normal heart are heterogeneous and are associated with the relative position of the caval veins. Patterns, other than 'typical' vortical flow, are more prevalent in the right atrium of those with cryptogenic stroke in the context of PFO. Left atrial flow patterns are more homogenous in normal hearts and show a relationship with flow arising from the left

Quasielastic knock out of light fragments from 12C and 16O by intermediate energy pions

International Nuclear Information System (INIS)

Abramov, B.M.; Borodin, Yu.A.; Bulychev, S.A.

2006-01-01

Using 0.72 GeV s -1 pulse π - -meson beam one studied the quasi-elastic knocking out of deuterons and of tritons from 12 C and 16 O nuclei. One derived the quasi-deuteron intranuclear motion pulse distributions, the residual nucleus excitation energy spectra and the effective number of quasi-deuterons. The parameters of quasi-deuteron intranuclear motion pulse distributions are in line with the measurement results for other beams. The effective numbers of quasi-deuterons in nuclei from 6 Li up to 16 O do not depend on the atomic number. One observed knocking out of tritons from the mentioned nuclei enabling to evaluate the cross section of elastic pion-triton backscattering [ru

Simultaneous measurement of instantaneous heart rate and chest wall plethysmography in short-term, metronome guided heart rate variability studies: suitability for assessment of autonomic dysfunction.

Science.gov (United States)

Perring, S; Jones, E

2003-08-01

Instantaneous heart rate and chest wall motion were measured using a 3-lead ECG and an air pressure chest wall plethysmography system. Chest wall plethysmography traces were found to accurately represent the breathing pattern as measured by spirometry (average correlation coefficient 0.944); though no attempt was made to calibrate plethysmography voltage output to tidal volume. Simultaneous measurements of heart rate and chest wall motion were made for short periods under metronome guided breathing at 6 breaths per minute. The average peak to trough heart rate change per breath cycle (AVEMAX) and maximum correlation between heart rate and breathing cycle (HRBRCORR) were measured. Studies of 44 normal volunteers indicated clear inverse correlation of heart rate variability parameters with age (AVEMAX R = -0.502, P < 0.001) but no significant change in HRBRCORR with age (R = -0.115). Comparison of normal volunteers with diabetics with no history of symptoms associated with autonomic failure indicated significant lower heart rate variability in diabetics (P = 0.005 for AVEMAX) and significantly worse correlation between heart rate and breathing (P < 0.001 for HRBRCORR). Simultaneous measurement of heart rate and breathing offers the possibility of more sensitive diagnosis of autonomic failure in a simple bedside test and gives further insight into the nature of cardio-ventilatory coupling.

Excited states of virtual clusters in a nucleus and the processes of quasi-elastic cluster knock-out at high energies

International Nuclear Information System (INIS)

Golovanova, N.F.; Il'in, I.M.; Neudatchin, V.G.; Smirnov, Yu.F.; Tchuvil'sky, Yu.M.

1976-01-01

The quasi-elastic knock-out of nucleon clusters from nuclei by an incident high-energy hadron is considered within the framework of the Glauber-Sitenko multiple scattering theory. It is shown that the significant contribution to the cross section for the process comes not only from the hadron elastic scattering by a nonexcited virtual cluster but also from collisions with an excited virtual cluster, accompanied by de-excitation of this cluster. This necessitates modification of the usual theory of quasi-elastic cluster knock-out. First, the angular correlations of the knocked-out cluster and scattered hadron are no longer determined by the momentum distribution of the cluster in the nucleus. They are determined by another form factor F(q) which can be called the modified momentum distribution. Secondly, the meaning and values of the effective numbers of clusters Nsup(eff) have been changed. Thirdly, the characteristics of the processes depend not only on the modulus of momentum q, which the cluster had in the nucleus, but also on its direction relative to an incident beam. A method has been developed for the calculation of the fractional parentage coefficients, which are necessary for the calculation of the cluster knock-out from the p-shell nuclei. (Auth.)

Association between Polymorphism of Endothelial Nitric Oxide Synthase Gene (Glu298Asp) and Chronic Heart Failure in Patients with Ischemic Heart Disease and Obesity

OpenAIRE

O.I. Kadykova; P.P. Kravchun

2016-01-01

The article reviewed the links between polymorphism of endothelial nitric oxide synthase gene (Glu298Asp) and the development and progression of chronic heart failure in patients with ischemic heart disease and obesity. There has been a comprehensive survey of 222 patients with ischemic heart disease. Comparison group consisted of 115 patients with ischemic heart disease with normal body weight. The control group included 35 healthy individuals. G allele and genotype G/G polymorphism of the g...

LatY136F knock-in mouse model for human IgG4-related disease.

Science.gov (United States)

Yamada, Kazunori; Zuka, Masahiko; Ito, Kiyoaki; Mizuguchi, Keishi; Kakuchi, Yasushi; Onoe, Tamehito; Suzuki, Yasunori; Yamagishi, Masakazu; Izui, Shozo; Malissen, Marie; Malissen, Bernard; Kawano, Mitsuhiro

2018-01-01

The adaptor protein Linker for activation of T cell (LAT) is a key signaling hub used by the T cell antigen receptor. Mutant mice expressing loss-of-function mutations affecting LAT and including a mutation in which tyrosine 136 is replaced by a phenylalanine (LatY136F) develop lymphoproliferative disorder involving T helper type 2 effector cells capable of triggering a massive polyclonal B cell activation that leads to hypergammaglobulinemia G1 and E and to non-resolving inflammation and autoimmunity. The purpose of this study was to evaluate whether the phenotypes of LatY136F knock-in mice resemble the immunohistopathological features of immunoglobulin G4-related disease (IgG4-RD). LatY136F knock-in mice were sacrificed at 4-20 weeks of age, and pancreas, kidney, salivary gland and lung were obtained. All organs were stained with hematoxylin-eosin and with Azan for estimation of collagen in fibrosis, and the severity scores of inflammation and fibrosis were evaluated. Immunostainings were performed to analyze the types of infiltrating cells. In addition, the effects of corticosteroid treatment on the development of tissue lesions and serum levels of IgG1 were assessed. Tissue lesions characterized by inflammatory mononuclear cell infiltration and fibrosis were detected in pancreas, kidney, and salivary gland starting from 6 weeks of age. Immunostainings showed pronounced infiltration of plasma cells, CD4-positive T cells, and macrophages. Infiltrating plasma cells predominantly expressed IgG1. The extent of inflammation in pancreas and salivary glands was markedly reduced by corticosteroid treatment. LatY136F knock-in mice displayed increased production of Th2-type IgG1 (a homologue of human IgG4) and developed multiple organ tissue lesions reminiscent of those seen in patients with IgG4-RD. Moreover, the development of these tissue lesions was highly sensitive to corticosteroid treatment like in IgG4-RD. For these reasons we consider the LatY136F knock-in mouse

Knocking out the MFE-2 gene of Candida bombicola leads to improved medium-chain sophorolipid production.

Science.gov (United States)

Van Bogaert, Inge N A; Sabirova, Julia; Develter, Dirk; Soetaert, Wim; Vandamme, Erick J

2009-06-01

The nonpathogenic yeast Candida bombicola synthesizes sophorolipids. These biosurfactants are composed of the disaccharide sophorose linked to a long-chain hydroxy fatty acid and have potential applications in the food, pharmaceutical, cosmetic and cleaning industries. In order to expand the range of application, a shift of the fatty acid moiety towards medium-chain lengths would be recommendable. However, the synthesis of medium-chain sophorolipids by C. bombicola is a challenging objective. First of all, these sophorolipids can only be obtained by fermentations on unconventional carbon sources, which often have a toxic effect on the cells. Furthermore, medium-chain substrates are partially metabolized in the beta-oxidation pathway. In order to redirect unconventional substrates towards sophorolipid synthesis, the beta-oxidation pathway was blocked on the genome level by knocking out the multifunctional enzyme type 2 (MFE-2) gene. The total gene sequence of the C. bombicola MFE-2 (6033 bp) was cloned (GenBank accession number EU371724), and the obtained nucleotide sequence was used to construct a knock-out cassette. Several knock-out mutants with the correct geno- and phenotype were evaluated in a fermentation on 1-dodecanol. All mutants showed a 1.7-2.9 times higher production of sophorolipids, indicating that in those strains the substrate is redirected towards the sophorolipid synthesis.

Developing a de novo targeted knock-in method based on in utero electroporation into the mammalian brain.

Science.gov (United States)

Tsunekawa, Yuji; Terhune, Raymond Kunikane; Fujita, Ikumi; Shitamukai, Atsunori; Suetsugu, Taeko; Matsuzaki, Fumio

2016-09-01

Genome-editing technology has revolutionized the field of biology. Here, we report a novel de novo gene-targeting method mediated by in utero electroporation into the developing mammalian brain. Electroporation of donor DNA with the CRISPR/Cas9 system vectors successfully leads to knock-in of the donor sequence, such as EGFP, to the target site via the homology-directed repair mechanism. We developed a targeting vector system optimized to prevent anomalous leaky expression of the donor gene from the plasmid, which otherwise often occurs depending on the donor sequence. The knock-in efficiency of the electroporated progenitors reached up to 40% in the early stage and 20% in the late stage of the developing mouse brain. Furthermore, we inserted different fluorescent markers into the target gene in each homologous chromosome, successfully distinguishing homozygous knock-in cells by color. We also applied this de novo gene targeting to the ferret model for the study of complex mammalian brains. Our results demonstrate that this technique is widely applicable for monitoring gene expression, visualizing protein localization, lineage analysis and gene knockout, all at the single-cell level, in developmental tissues. © 2016. Published by The Company of Biologists Ltd.

Chemical Methods to Knock Down the Amyloid Proteins

Directory of Open Access Journals (Sweden)

Na Gao

2017-06-01

Full Text Available Amyloid proteins are closely related with amyloid diseases and do tremendous harm to human health. However, there is still a lack of effective strategies to treat these amyloid diseases, so it is important to develop novel methods. Accelerating the clearance of amyloid proteins is a favorable method for amyloid disease treatment. Recently, chemical methods for protein reduction have been developed and have attracted much attention. In this review, we focus on the latest progress of chemical methods that knock down amyloid proteins, including the proteolysis-targeting chimera (PROTAC strategy, the “recognition-cleavage” strategy, the chaperone-mediated autophagy (CMA strategy, the selectively light-activatable organic and inorganic molecules strategy and other chemical strategies.

Knocking out P2X receptors reduces transmitter secretion in taste buds.

Science.gov (United States)

Huang, Yijen A; Stone, Leslie M; Pereira, Elizabeth; Yang, Ruibiao; Kinnamon, John C; Dvoryanchikov, Gennady; Chaudhari, Nirupa; Finger, Thomas E; Kinnamon, Sue C; Roper, Stephen D

2011-09-21

In response to gustatory stimulation, taste bud cells release a transmitter, ATP, that activates P2X2 and P2X3 receptors on gustatory afferent fibers. Taste behavior and gustatory neural responses are largely abolished in mice lacking P2X2 and P2X3 receptors [P2X2 and P2X3 double knock-out (DKO) mice]. The assumption has been that eliminating P2X2 and P2X3 receptors only removes postsynaptic targets but that transmitter secretion in mice is normal. Using functional imaging, ATP biosensor cells, and a cell-free assay for ATP, we tested this assumption. Surprisingly, although gustatory stimulation mobilizes Ca(2+) in taste Receptor (Type II) cells from DKO mice, as from wild-type (WT) mice, taste cells from DKO mice fail to release ATP when stimulated with tastants. ATP release could be elicited by depolarizing DKO Receptor cells with KCl, suggesting that ATP-release machinery remains functional in DKO taste buds. To explore the difference in ATP release across genotypes, we used reverse transcriptase (RT)-PCR, immunostaining, and histochemistry for key proteins underlying ATP secretion and degradation: Pannexin1, TRPM5, and NTPDase2 (ecto-ATPase) are indistinguishable between WT and DKO mice. The ultrastructure of contacts between taste cells and nerve fibers is also normal in the DKO mice. Finally, quantitative RT-PCR show that P2X4 and P2X7, potential modulators of ATP secretion, are similarly expressed in taste buds in WT and DKO taste buds. Importantly, we find that P2X2 is expressed in WT taste buds and appears to function as an autocrine, positive feedback signal to amplify taste-evoked ATP secretion.

Age- and region-specific imbalances of basal amino acids and monoamine metabolism in limbic regions of female Fmr1 knock-out mice.

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Gruss, Michael; Braun, Katharina

2004-07-01

The Fragile X syndrome, a common form of mental retardation in humans, originates from the loss of expression of the Fragile X mental retardation gene leading to the absence of the encoded Fragile X mental retardation protein 1 (FMRP). A broad pattern of morphological and behavioral abnormalities is well described for affected humans as well as Fmr1 knock-out mice, a transgenic animal model for the human Fragile X syndrome. In the present study, we examined neurochemical differences between female Fmr1 knock-out and wildtype mice with particular focus on neurotransmission. Significant age- and region-specific differences of basal tissue neurotransmitter and metabolite levels measured by high performance liquid chromatography were found. Those differences were more numerous in juvenile animals (postnatal day (PND) 28-31) compared to adults (postnatal day 209-221). In juvenile female knock-out mice, especially aspartate and taurine were increased in cortical regions, striatum, cerebellum, and brainstem. Furthermore, compared to the wildtype animals, the juvenile knock-out mice displayed an increased level of neuronal inhibition in the hippocampus and brainstem reflected by decreased ratios of (aspartate + glutamate)/(taurine + GABA), as well as an increased dopamine (DA) turnover in cortical regions, striatum, and hippocampus. These results provide the first evidence that the lack of FMRP expression in female Fmr1 knock-out mice is accompanied by age-dependent, region-specific alterations in brain amino acids, and monoamine turnover, which might be related to the reported synaptical and behavioural alterations in these animals.

Effect of thermal 3He minorities on knock-on tail formation and the resulting neutron emission spectrum modification in deuterium-tritium plasmas

International Nuclear Information System (INIS)

Matsuura, H; Nakao, Y; Nakamura, M; Mitarai, O

2011-01-01

The knock-on tail formations in fuel-ion velocity distribution functions by energetic alpha particles (by the T(d,n) 4 He reaction) and protons (by the D(d,p)T and 3 He(d,p) 4 He reactions) are investigated by simultaneously solving the Boltzmann-Fokker-Planck (BFP) equations for deuteron, triton, 3 He, alpha particle and proton in an ITER-like (DT) plasma admixed with a small amount of 3 He. As a result of the 3 He inclusion, a fraction of the transferred energy from energetic ions to thermal deuterons and tritons via nuclear plus interference (NI) scattering is reduced. Owing to the NI scattering of the energetic protons by fuel ions, the latter are knocked up to higher energies. The knocking-up effect of fuel ions is enhanced with increasing 3 He concentration. It is shown that if 3 He with relative concentration of 4.2%, i.e. n 3 He /n e =0.042, is included in T e = 20 keV, n e = 9.5 x 10 19 m -3 plasma, the magnitude of the knock-on tail in deuteron distribution function in 300 keV-3 MeV energy range is reduced by about 15% from the value when 3 He is not externally supplied. Such knock-on tail reduction also results in alternation of the non-Gaussian neutron emission spectrum with energies less than ∼13 MeV and above ∼15 MeV.

Depressed Frank-Starling mechanism in the left ventricular muscle of the knock-in mouse model of dilated cardiomyopathy with troponin T deletion mutation ΔK210.

Science.gov (United States)

Inoue, Takahiro; Kobirumaki-Shimozawa, Fuyu; Kagemoto, Tatsuya; Fujii, Teruyuki; Terui, Takako; Kusakari, Yoichiro; Hongo, Kenichi; Morimoto, Sachio; Ohtsuki, Iwao; Hashimoto, Kazuhiro; Fukuda, Norio

2013-10-01

It has been reported that the Frank-Starling mechanism is coordinately regulated in cardiac muscle via thin filament "on-off" equilibrium and titin-based lattice spacing changes. In the present study, we tested the hypothesis that the deletion mutation ΔK210 in the cardiac troponin T gene shifts the equilibrium toward the "off" state and accordingly attenuate the sarcomere length (SL) dependence of active force production, via reduced cross-bridge formation. Confocal imaging in isolated hearts revealed that the cardiomyocytes were enlarged, especially in the longitudinal direction, in ΔK210 hearts, with striation patterns similar to those in wild type (WT) hearts, suggesting that the number of sarcomeres is increased in cardiomyocytes but the sarcomere length remains unaltered. For analysis of the SL dependence of active force, skinned muscle preparations were obtained from the left ventricle of WT and knock-in (ΔK210) mice. An increase in SL from 1.90 to 2.20μm shifted the mid-point (pCa50) of the force-pCa curve leftward by ~0.21pCa units in WT preparations. In ΔK210 muscles, Ca(2+) sensitivity was lower by ~0.37pCa units, and the SL-dependent shift of pCa50, i.e., ΔpCa50, was less pronounced (~0.11pCa units), with and without protein kinase A treatment. The rate of active force redevelopment was lower in ΔK210 preparations than in WT preparations, showing blunted thin filament cooperative activation. An increase in thin filament cooperative activation upon an increase in the fraction of strongly bound cross-bridges by MgADP increased ΔpCa50 to ~0.21pCa units. The depressed Frank-Starling mechanism in ΔK210 hearts is the result of a reduction in thin filament cooperative activation. © 2013.

Travel and Heart Disease

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... a game park for the day,” Gandy said. Plane Precautions Sitting immobile on long plane flights can slightly increase a normal person’s risk ... Disease (PAD) • Stroke • Vascular Health • Venous Thromboembolism (VTE) • Consumer Healthcare • Tools For Your Heart Health • Watch, Learn & ...

Conjoined twins: morphogenesis of the heart and a review.

Science.gov (United States)

Gilbert-Barness, Enid; Debich-Spicer, Diane; Opitz, John M

2003-08-01

Five cases of conjoined twins have been studied. These included three thoracopagus twins, one monocephalus diprosopus (prosop = face), and one dicephalus dipus dibrachus. The thoracopagus twins were conjoined only from the upper thorax to the umbilicus with a normal foregut. These three cases shared a single complex multiventricular heart, one with a four chambered heart with one atrium and one ventricle belonging to each twin with complex venous and arterial connection; two had a seven chambered heart with four atria and three ventricles. The mono-cephalus diprosopus twins had a single heart with tetralogy of Fallot. The dicephalus twins had two separate axial skeletons to the sacrum, two separate hearts were connected between the right atria with a shared inferior vena cava. Thoracopagus twinning is associated with complex cardiac malformations. The cardiac anlagen in cephalopagus or diprosopus are diverted and divided along with the entire rostral end of the embryonic disc and result in two relatively normal shared hearts. However, in thoracopagus twins the single heart is multiventricular and suggests very early union with fusion of the cardiac anlagen before significant differentiation. Cardiac morphogenesis in conjoined twins therefore appears to depend on the site of the conjoined fusion and the temporal and spatial influence that determines morphogenesis as well as abnormally oriented embryonic axes. Copyright 2003 Wiley-Liss, Inc.

Clinical evaluation of ischemic heart diagnosis

International Nuclear Information System (INIS)

Kamei, Fumio

1983-01-01

Attempt were made to detect the existence of myocardial ischemia by means of both radiographic and scintigraphic techniques. Firstly, a new polygraph was especially designed for selecting the arbitrary phases in a cardiac cycle at which the corresponding radiogram should be synchronously obtained. A comparative investigation on the difference between end-systolic and-diastolic cardiac transverse diameters revealed a remarkable difference of 3.6% in normal subjects and 0.6% in patients with ischemic heart disease. These data indicating the difference of overall heart size was reflected in local dyskinesis documentation of recently developed techniques. For daily clinical purposes, radiography of the chest based on synchronously selected phases would contribute to accurate diagnosis and treatment of heart disease. Secondly, scintigraphic display using intravenously injected thallium-201 was clinically applied. For detection of ischemia, comparative study was performed of initial image relative to selective coronary cineangiography and stress scintigraphy. The former indicated a good correlation of 90%, whereas the latter served to enhnace sensitivity. Sequential images (initial and delayed) facilitated the distinction of normal, necrotic, and ischemic areas. Scintigram was used for objective evaluation of coronary dilator (dilazep), either at immediate or follow-up stage. In the same way, it was also possible to indicate the effectiveness of sublingually given nitroglycerin by myocardial scintigram, where by significant increase of uptake was observed 20 minutes after administration. Rehabilitation after acute heart disease was discussed, especially on the peripheral effect. Ratio of the thigh muscle to myocardium shown in this study was useful fer objective evaluation. Another preliminary study is to separate normal coronary arteries from myocardial necrosis. (J.P.N.)

Clinical evaluation of ischemic heart diagnosis

Energy Technology Data Exchange (ETDEWEB)

Kamei, Fumio [Sendai Railway Hospital (Japan)

1983-09-01

Attempt were made to detect the existence of myocardial ischemia by means of both radiographic and scintigraphic techniques. Firstly, a new polygraph was especially designed for selecting the arbitrary phases in a cardiac cycle at which the corresponding radiogram should be synchronously obtained. A comparative investigation on the difference between end-systolic and-diastolic cardiac transverse diameters revealed a remarkable difference of 3.6% in normal subjects and 0.6% in patients with ischemic heart disease. These data indicating the difference of overall heart size was reflected in local dyskinesis documentation of recently developed techniques. For daily clinical purposes, radiography of the chest based on synchronously selected phases would contribute to accurate diagnosis and treatment of heart disease. Secondly, scintigraphic display using intravenously injected thallium-201 was clinically applied. For detection of ischemia, comparative study was performed of initial image relative to selective coronary cineangiography and stress scintigraphy. The former indicated a good correlation of 90%, whereas the latter served to enhance sensitivity. Sequential images (initial and delayed) facilitated the distinction of normal, necrotic, and ischemic areas. Scintigram was used for objective evaluation of coronary dilator (dilazep), either at immediate or follow-up stage. In the same way, it was also possible to indicate the effectiveness of sublingually given nitroglycerin by myocardial scintigram, where by significant increase of uptake was observed 20 minutes after administration. Rehabilitation after acute heart disease was discussed, especially on the peripheral effect. Ratio of the thigh muscle to myocardium shown in this study was useful for objective evaluation. Another preliminary study is to separate normal coronary arteries from myocardial necrosis.

Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury.

Science.gov (United States)

Sawicki, Konrad Teodor; Shang, Meng; Wu, Rongxue; Chang, Hsiang-Chun; Khechaduri, Arineh; Sato, Tatsuya; Kamide, Christine; Liu, Ting; Naga Prasad, Sathyamangla V; Ardehali, Hossein

2015-07-31

Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to nontransgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to nonischemic cardiomyopathy. Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a novel approach for protection against the

Analysis of different multiplicities and their interference in quasi-elastic cluster knock-out by fast hadrons

International Nuclear Information System (INIS)

Golovanova, N.F.; Ibraeva, E.T.; Neudatchin, V.G.

1978-01-01

Different multiplicities and their interference in hadron scattering have been investigated on the basis of a new dynamic approach to quasi-elastic knock-out of nucleon clusters by fast hadrons from light nuclei. It is shown that in the region of momentum transfer values p, where scattering multiplicities less than b are predominant, the effective numbers and form factors determined in Refs. 1) -- 3) no longer act as pure structural nuclear factors (b means the number of nucleons in the knocked-out cluster). These characteristics are significantly dependent on the process dynamics. Only in the region of values p, where the maximum hadron scattering multiplicity b is realized, the effective numbers and form factors do assume the purely structural meaning. (auth.)

Heart Failure Increases the Risk of Adverse Renal Outcomes in Patients With Normal Kidney Function.

Science.gov (United States)

George, Lekha K; Koshy, Santhosh K G; Molnar, Miklos Z; Thomas, Fridtjof; Lu, Jun L; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

2017-08-01

Heart failure (HF) is associated with poor cardiac outcomes and mortality. It is not known whether HF leads to poor renal outcomes in patients with normal kidney function. We hypothesized that HF is associated with worse long-term renal outcomes. Among 3 570 865 US veterans with estimated glomerular filtration rate (eGFR) ≥60 mL min -1 1.73 m -2 during October 1, 2004 to September 30, 2006, we identified 156 743 with an International Classification of Diseases , Ninth Revision , diagnosis of HF. We examined the association of HF with incident chronic kidney disease (CKD), the composite of incident CKD or mortality, and rapid rate of eGFR decline (slopes steeper than -5 mL min -1 1.73 m -2 y -1 ) using Cox proportional hazard analyses and logistic regression. Adjustments were made for various confounders. The mean±standard deviation baseline age and eGFR of HF patients were 68±11 years and 78±14 mL min -1 1.73 m -2 and in patients without HF were 59±14 years and 84±16 mL min -1 1.73 m -2 , respectively. HF patients had higher prevalence of hypertension, diabetes mellitus, cardiac, peripheral vascular and chronic lung diseases, stroke, and dementia. Incidence of CKD was 69.0/1000 patient-years in HF patients versus 14.5/1000 patient-years in patients without HF, and 22% of patients with HF had rapid decline in eGFR compared with 8.5% in patients without HF. HF patients had a 2.12-, 2.06-, and 2.13-fold higher multivariable-adjusted risk of incident CKD, composite of CKD or mortality, and rapid eGFR decline, respectively. HF is associated with significantly higher risk of incident CKD, incident CKD or mortality, and rapid eGFR decline. Early diagnosis and management of HF could help reduce the risk of long-term renal complications. © 2017 American Heart Association, Inc.

[Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart disease.

DEFF Research Database (Denmark)

Holst, Anders Gaarsdal; Tfelt-Hansen, 1jacob; Olesen, Morten S

2010-01-01

Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart disease, which can lead to life-threatening ventricular arrhythmias in patients with a structurally normal heart. The age of onset is usually between two and 12 years and the initial symptom is frequently syncope...

"When Do I Knock on the Hotel Room Door?": The MLA Conference Job Interview.

Science.gov (United States)

Emmerson, Richard K.

1995-01-01

Offers advice to potential interviewees attending an MLA conference. Cautions the interviewee to arrive for the appointment early, but not to knock until the time of the appointment. Advises interviewees to answer questions briefly and to let the committee set the pace of the interview. (PA)

The clinical significance of detection to heart rate deceleration capacity and heart rate variability in patients with chronic heart failure

Directory of Open Access Journals (Sweden)

Jiang-rong Zhou

2015-01-01

Full Text Available Objective: To study the change of heart rate deceleration capacity ( DC and heart rate variability in patients with chronic heart failure (CHF and its relationship with left ventricular ejection fraction (LVEF. Methods: DC, LVEF, time and frequency domain parameters of HRV were measured in 66 patients with CHF and 34 healthy adults (control group by using 24h Holter recordings and Echocardiography. The standard deviation of normal R-R intervals( SDNN, squares of differences between adjacent NN intervals ( RMSSD，low frequency power( LFn and high frequency power( HFn and the changes of LVEF were compared between  the two groups，the relationship between DC，LVEF and HRV were studied in patients with CHF. Results: The median value of DC in the patients with CHF was significantly lower than that in control group( 3.1 ± 2.4 ms vs 7.2 ± 1.3 ms，P <0.01．Incidence of abnormal DC in the CHF group was 57.5%，which was significantly higher than that in the control group (P <0.01．The HRV index, including SDNN、RMSSD、LFn、HFn, in the CHF group was significantly lower than that in normal control group (P < 0.01. Significant positive correlation between HRV index and LVEF were confirmed (P < 0.01. Conclusions: DC and HRV index are lower in patients with CHF and have a good correlation with the left ventricular ejection fraction.

Characterisation of a C1qtnf5 Ser163Arg knock-in mouse model of late-onset retinal macular degeneration.

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Xinhua Shu

Full Text Available A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse "knock-in" model carrying the Ser163Arg mutation in the orthologous murine C1qtnf5 gene by site-directed mutagenesis and homologous recombination into mouse embryonic stem cells. Biochemical, immunological, electron microscopic, fundus autofluorescence, electroretinography and laser photocoagulation analyses were used to characterise the mouse model. Heterozygous and homozygous knock-in mice showed no significant abnormality in any of the above measures at time points up to 2 years. This result contrasts with another C1qtnf5 Ser163Arg knock-in mouse which showed most of the features of L-ORMD but differed in genetic background and targeting construct.

A combination method for simulation of secondary knock-on atoms of boron carbide induced by neutron irradiation in SPRR-300

International Nuclear Information System (INIS)

Wu, Jian-Chun; Feng, Qi-Jie; Liu, Xian-Kun; Zhan, Chang-Yong; Zou, Yu; Liu, Yao-Guang

2016-01-01

A multiscale sequence of simulation should be used to predict properties of materials under irradiation. Binary collision theory and molecular dynamics (MDs) method are commonly used to characterize the displacement cascades induced by neutrons in a material. In order to reduce the clock time spent for the MD simulation of damages induced by high-energy primary knock-on atoms (PKAs), the damage zones were split into sub-cascade according to the sub-cascade formation criteria. Two well-known codes, Geant4 and TRIM, were used to simulate high-energy PKA-induced cascades in B_4C and then produce the secondary knock-on atom (SKA) energy spectrum. It has been found that both high-energy primary knock-on B and C atoms move a long range in the boron carbide. These atoms produce sub-cascades at the tip of trajectory. The energy received by most of the SKAs is <10 keV, which can be used as input to reduce the clock time spent for MD simulation.

[3H]-nitrendipine binding in membranes obtained from hypoxic and reoxygenated heart.

Science.gov (United States)

Matucci, R; Bennardini, F; Sciammarella, M L; Baccaro, C; Stendardi, I; Franconi, F; Giotti, A

1987-04-01

We compared the binding properties of [3H]-nitrendipine in heart membranes from normal guinea-pig heart and from hypoxic or hypoxic and reoxygenated heart. The [3H]-nitrendipine binds a single class of high capacity (Bmax 667.2 +/- 105.2) with high affinity (KD 0.14 +/- 0.02) binding sites. By contrast, in membranes of hypoxic and reoxygenated heart the Bmax decreases significantly while it remains unaffected during hypoxia. Xanthinoxidase activity is increased in hypoxic-reoxygenated hearts.

Numerical and Experimental Investigation of Combustion and Knock in a Dual Fuel Gas/Diesel Compression Ignition Engine

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A. Gharehghani

2012-01-01

Full Text Available Conventional compression ignition engines can easily be converted to a dual fuel mode of operation using natural gas as main fuel and diesel oil injection as pilot to initiate the combustion. At the same time, it is possible to increase the output power by increasing the diesel oil percentage. A detailed performance and combustion characteristic analysis of a heavy duty diesel engine has been studied in dual fuel mode of operation where natural gas is used as the main fuel and diesel oil as pilot. The influence of intake pressure and temperature on knock occurrence and the effects of initial swirl ratio on heat release rate, temperature-pressure and emission levels have been investigated in this study. It is shown that an increase in the initial swirl ratio lengthens the delay period for auto-ignition and extends the combustion period while it reduces NOx. There is an optimum value of the initial swirl ratio for a certain mixture intake temperature and pressure conditions that can achieve high thermal efficiency and low NOx emissions while decreases the tendency to knock. Simultaneous increase of intake pressure and initial swirl ratio could be the solution to power loss and knock in dual fuel engine.

Knock-in fibroblasts and transgenic blastocysts for expression of human FGF2 in the bovine β-casein gene locus using CRISPR/Cas9 nuclease-mediated homologous recombination.

Science.gov (United States)

Jeong, Young-Hee; Kim, Yeong Ji; Kim, Eun Young; Kim, Se Eun; Kim, Jiwoo; Park, Min Jee; Lee, Hong-Gu; Park, Se Pill; Kang, Man-Jong

2016-06-01

Many transgenic domestic animals have been developed to produce therapeutic proteins in the mammary gland, and this approach is one of the most important methods for agricultural and biomedical applications. However, expression and secretion of a protein varies because transgenes are integrated at random sites in the genome. In addition, distal enhancers are very important for transcriptional gene regulation and tissue-specific gene expression. Development of a vector system regulated accurately in the genome is needed to improve production of therapeutic proteins. The objective of this study was to develop a knock-in system for expression of human fibroblast growth factor 2 (FGF2) in the bovine β-casein gene locus. The F2A sequence was fused to the human FGF2 gene and inserted into exon 3 of the β-casein gene. We detected expression of human FGF2 mRNA in the HC11 mouse mammary epithelial cells by RT-PCR and human FGF2 protein in the culture media using western blot analysis when the knock-in vector was introduced. We transfected the knock-in vector into bovine ear fibroblasts and produced knock-in fibroblasts using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. Moreover, the CRISPR/Cas9 system was more efficient than conventional methods. In addition, we produced knock-in blastocysts by somatic cell nuclear transfer using the knock-in fibroblasts. Our knock-in fibroblasts may help to create cloned embryos for development of transgenic dairy cattle expressing human FGF2 protein in the mammary gland via the expression system of the bovine β-casein gene.

Ventilatory disorders in heart failure

NARCIS (Netherlands)

Güder, G.

2017-01-01

Introduction: Chronic obstructive pulmonary disease (COPD), heart failure (HF) or both syndromes are the most common reasons for dyspnea in the elderly. Currently there is no standard to diagnose COPD and multiple definitions (fixed ratio [GOLD], lower limit of normal [LLN]) are discussed. Further,

A case of peripartum heart failure

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Annalisa Vinci

2008-03-01

Full Text Available A 32-year-old woman was admitted in congestive heart failure (CHF 3 days after delivery. She had no history of cardiovascular disease and impaired left ventricular Ejection Fraction (EF 35%. She underwent complete heart catheterisation, selective coronary angiography and right ventricular endomyocardial biopsy (EMB.Coronary arteries were normal and EMB revealed active virus negative myocarditis. Serum was positive for anti-heart autoantibodies (AHA. Thus myocarditis was classified as autoimmune and the patient was treated with immunosuppressive therapy, with clinical and hemodynamic improvement. At 27 months follow-up EMB showed healed myocarditis. Peripartum cardiomyopathy (PPCM is a rare disorder in which left ventricular dysfunction and heart failure occur in the peripartum period in previously healthy women. The etiology is still unknown but a sizable proportion of patients may have an underlying organ-specific autoimmune myocarditis.

CRISPR/Cas9 allows efficient and complete knock-in of a destabilization domain-tagged essential protein in a human cell line, allowing rapid knockdown of protein function.

Science.gov (United States)

Park, Arnold; Won, Sohui T; Pentecost, Mickey; Bartkowski, Wojciech; Lee, Benhur

2014-01-01

Although modulation of protein levels is an important tool for study of protein function, it is difficult or impossible to knockdown or knockout genes that are critical for cell growth or viability. For such genes, a conditional knockdown approach would be valuable. The FKBP protein-based destabilization domain (DD)-tagging approach, which confers instability to the tagged protein in the absence of the compound Shield-1, has been shown to provide rapid control of protein levels determined by Shield-1 concentration. Although a strategy to knock-in DD-tagged protein at the endogenous loci has been employed in certain parasite studies, partly due to the relative ease of knock-in as a result of their mostly haploid lifecycles, this strategy has not been demonstrated in diploid or hyperploid mammalian cells due to the relative difficulty of achieving complete knock-in in all alleles. The recent advent of CRISPR/Cas9 homing endonuclease-mediated targeted genome cleavage has been shown to allow highly efficient homologous recombination at the targeted locus. We therefore assessed the feasibility of using CRISPR/Cas9 to achieve complete knock-in to DD-tag the essential gene Treacher Collins-Franceschetti syndrome 1 (TCOF1) in human 293T cells. Using a double antibiotic selection strategy to select clones with at least two knock-in alleles, we obtained numerous complete knock-in clones within three weeks of initial transfection. DD-TCOF1 expression in the knock-in cells was Shield-1 concentration-dependent, and removal of Shield-1 resulted in destabilization of DD-TCOF1 over the course of hours. We further confirmed that the tagged TCOF1 retained the nucleolar localization of the wild-type untagged protein, and that destabilization of DD-TCOF1 resulted in impaired cell growth, as expected for a gene implicated in ribosome biogenesis. CRISPR/Cas9-mediated homologous recombination to completely knock-in a DD tag likely represents a generalizable and efficient strategy to

No-recoil approximation to the knock-on exchange potential in the double folding model for heavy-ion collisions

International Nuclear Information System (INIS)

Hagino, K.; Takehi, T.; Takigawa, N.

2006-01-01

We propose the no-recoil approximation, which is valid for heavy systems, for a double folding nucleus-nucleus potential. With this approximation, the nonlocal knock-on exchange contribution becomes a local form. We discuss the applicability of this approximation for elastic scattering of the 6 Li + 40 Ca system. We find that, for this and heavier systems , the no-recoil approximation works as good as another widely used local approximation that employs a local plane wave for the relative motion between the colliding nuclei. We also compare the results of the no-recoil calculations with those of the zero-range approximation often used to handle the knock-on exchange effect

Effect of biological factors during functional scintigraphy of the heart

Energy Technology Data Exchange (ETDEWEB)

Breuel, H P; Emrich, D; Luig, H [Goettingen Univ. (F.R. Germany). Abt. fuer Nuklearmedizin

1976-07-01

The parameters relating to functional scintigraphy of the heart (average circulation time, peak time) depend not only on the method (injection technique, radiopharmaceutical), but also on biological factors. Failure to take these into consideration may result in an erroneous interpretation of the findings. Circulation time in normal children aged 6 to 14 years, as determined by isotope methods is significantly shorter than in normal adults. Patients with compensated heart disease, as well trained athletes, show significant increase in all portions of the circulation time, when compared with normals of similar ages. This indicates that deviation in the haemodynamics of the circulation as shown by functional scintigraphy, can only be interpreted in the light of clinical findings.

Cardiac development : the posterior heart field and atrioventricular reentry tachycardia

NARCIS (Netherlands)

Hahurij, Nathan Dominggus

2011-01-01

This thesis is separated in two parts (Part I and Part II) in which normal and abnormal heart development are studied and related to congenital heart disease, in particular to the etiology of supraventricular arrhythmias in fetuses and neonates. Part I describes the development of the posterior

Ischemic preconditioning fails to confer additional protection against ischemia-reperfusion injury in the hypothyroid rat heart.

Science.gov (United States)

Mourouzis, I; Dimopoulos, A; Saranteas, T; Tsinarakis, N; Livadarou, E; Spanou, D; Kokkinos, A D; Xinaris, C; Pantos, C; Cokkinos, D V

2009-01-01

There is accumulating evidence showing that ischemic preconditioning (PC) may lose its cardioprotective effect in the diseased states. The present study investigated whether PC can be effective in hypothyroidism, a clinical condition which is common and often accompanies cardiac diseases such as heart failure and myocardial infarction. Hypothyroidism was induced in rats by 3-week administration of 6n-propyl-2-thiouracil in water (0.05 %). Normal and hypothyroid hearts (HYPO) were perfused in Langendorff mode and subjected to 20 min of zero-flow global ischemia and 45 min of reperfusion. A preconditioning protocol (PC) was also applied prior to ischemia. HYPO hearts had significantly improved post-ischemic recovery of left ventricular developed pressure, end-diastolic pressure and reduced lactate dehydrogenase release. Furthermore, phospho-JNK and p38 MAPK levels after ischemia and reperfusion were 4.0 and 3.0 fold lower in HYPO as compared to normal hearts (Phearts. PC improved the post-ischemic recovery of function and reduced the extent of injury in normal hearts but had no additional effect on the hypothyroid hearts. This response, in the preconditioned normal hearts, resulted in 2.5 and 1.8 fold smaller expression of the phospho-JNK and phospho-p38 MAPK levels at the end of reperfusion, as compared to non-PC hearts (Phearts, no additional reduction in the phosphorylation of these kinases was observed after PC. Hypothyroid hearts appear to be tolerant to ischemia-reperfusion injury. This response may be, at least in part, due to the down-regulation of ischemia-reperfusion induced activation of JNKs and p38 MAPK kinases. PC is not associated with further reduction in the activation of these kinases in the hypothyroid hearts and fails to confer added protection in those hearts.

Prevalence of symptomatic heart failure with reduced and with normal ejection fraction in an elderly general population-the CARLA study.

Directory of Open Access Journals (Sweden)

Daniel Tiller

Full Text Available BACKGROUND/OBJECTIVES: Chronic heart failure (CHF is one of the most important public health concerns in the industrialized world having increasing incidence and prevalence. Although there are several studies describing the prevalence of heart failure with reduced ejection fraction (HFREF and heart failure with normal ejection fraction (HFNEF in selected populations, there are few data regarding the prevalence and the determinants of symptomatic heart failure in the general population. METHODS: Cross-sectional data of a population-based German sample (1,779 subjects aged 45-83 years were analyzed to determine the prevalence and determinants of chronic SHF and HFNEF defined according to the European Society of Cardiology using symptoms, echocardiography and serum NT-proBNP. Prevalence was age-standardized to the German population as of December 31st, 2005. RESULTS: The overall age-standardized prevalence of symptomatic CHF was 7.7% (95%CI 6.0-9.8 for men and 9.0% (95%CI 7.0-11.5 for women. The prevalence of CHF strongly increased with age from 3.0% among 45-54- year-old subjects to 22.0% among 75-83- year-old subjects. Symptomatic HFREF could be shown in 48% (n = 78, symptomatic HFNEF in 52% (n = 85 of subjects with CHF. The age-standardized prevalence of HFREF was 3.8 % (95%CI 2.4-5.8 for women and 4.6 % (95%CI 3.6-6.3 for men. The age-standardized prevalence of HFNEF for women and men was 5.1 % (95%CI 3.8-7.0 and 3.0 % (95%CI 2.1-4.5, respectively. Persons with CHF were more likely to have hypertension (PR = 3.4; 95%CI 1.6-7.3 or to have had a previous myocardial infarction (PR = 2.5, 95%CI 1.8-3.5. CONCLUSION: The prevalence of symptomatic CHF appears high in this population compared with other studies. While more women were affected by HFNEF than men, more male subjects suffered from HFREF. The high prevalence of symptomatic CHF seems likely to be mainly due to the high prevalence of cardiovascular risk factors in this population.

Downy mildew of Double Knock Out® rose caused by Peronospora sparsa in Maryland

Science.gov (United States)

Roses are one of the most popular and economically important ornamental plants worldwide. In the last 17 years, Knock Out® roses (Rosa x 'Radtko') have been widely used in public and private gardens across the U.S. due to their disease resistance, self-cleaning, drought tolerance and multiple-bloomi...

A Novel Mgp-Cre Knock-In Mouse Reveals an Anticalcification/Antistiffness Candidate Gene in the Trabecular Meshwork and Peripapillary Scleral Region.

Science.gov (United States)

Borrás, Teresa; Smith, Matthew H; Buie, LaKisha K

2015-04-01

Soft tissue calcification is a pathological condition. Matrix Gla (MGP) is a potent mineralization inhibitor secreted by cartilage chondrocytes and arteries' vascular smooth muscle cells. Mgp knock-out mice die at 6 weeks due to massive arterial calcification. Arterial calcification results in arterial stiffness and higher systolic blood pressure. Intriguingly, MGP was highly abundant in trabecular meshwork (TM). Because tissue stiffness is relevant to glaucoma, we investigated which additional eye tissues use Mgp's function using knock-in mice. An Mgp-Cre-recombinase coding sequence (Cre) knock-in mouse, containing Mgp DNA plus an internal ribosomal entry site (IRES)-Cre-cassette was generated by homologous recombination. Founders were crossed with Cre-mediated reporter mouse R26R-lacZ. Their offspring expresses lacZ where Mgp is transcribed. Eyes from MgpCre/+;R26RlacZ/+ (Mgp-lacZ knock-in) and controls, 1 to 8 months were assayed for β-gal enzyme histochemistry. As expected, Mgp-lacZ knock-in's TM was intensely blue. In addition, this mouse revealed high specific expression in the sclera, particularly in the peripapillary scleral region (ppSC). Ciliary muscle and sclera above the TM were also positive. Scleral staining was located immediately underneath the choroid (chondrocyte layer), began midsclera and was remarkably high in the ppSC. Cornea, iris, lens, ciliary body, and retina were negative. All mice exhibited similar staining patterns. All controls were negative. Matrix Gla's restricted expression to glaucoma-associated tissues from anterior and posterior segments suggests its involvement in the development of the disease. Matrix Gla's anticalcification/antistiffness properties in the vascular tissue, together with its high TM and ppCS expression, place this gene as a strong candidate for TM's softness and sclera's stiffness regulation in glaucoma.

Expression of inactive glutathione peroxidase 4 leads to embryonic lethality, and inactivation of the Alox15 gene does not rescue such knock-in mice.

Science.gov (United States)

Brütsch, Simone Hanna; Wang, Chi Chiu; Li, Lu; Stender, Hannelore; Neziroglu, Nilgün; Richter, Constanze; Kuhn, Hartmut; Borchert, Astrid

2015-02-01

Glutathione peroxidases (Gpx) and lipoxygenases (Alox) are functional counterplayers in the metabolism of hydroperoxy lipids that regulate cellular redox homeostasis. Gpx4 is a moonlighting protein that has been implicated not only as an enzyme in anti-oxidative defense, gene expression regulation, and programmed cell death, but also as a structural protein in spermatogenesis. Homozygous Gpx4 knock-out mice are not viable, but molecular reasons for intrauterine lethality are not completely understood. This study was aimed at investigating whether the lack of catalytic activity or the impaired function as structural protein is the dominant reason for embryonic lethality. We further explored whether the pro-oxidative enzyme mouse 12/15 lipoxygenase (Alox15) plays a major role in embryonic lethality of Gpx4-deficient mice. To achieve these goals, we first created knock-in mice, which express a catalytically inactive Gpx4 mutant (Sec46Ala). As homozygous Gpx4-knock-out mice Sec46Ala-Gpx4(+/+) knock-in animals are not viable but undergo intrauterine resorption between embryonic day 6 and 7 (E6-7). In contrast, heterozygous knock-in mice (Sec46Ala-Gpx4(-/+)) are viable, fertile and do not show major phenotypic alterations. Interestingly, homozygous Alox15 deficiency did not rescue the U46A-Gpx4(+/+) mice from embryonic lethality. In fact, when heterozygous U46A-Gpx4(-/+) mice were stepwise crossed into an Alox15-deficent background, no viable U46A-Gpx4(+/+)+Alox15(-/-) individuals were obtained. However, we were able to identify U46A-Gpx4(+/+)+Alox15(-/-) embryos in the state of resorption around E7. These data suggest that the lack of catalytic activity is the major reason for the embryonic lethality of Gpx4(-/-) mice and that systemic inactivation of the Alox15 gene does not rescue homozygous knock-in mice expressing catalytically silent Gpx4.

/sup 201/Thallium scintimetry of the heart as a new method for functional assessment in coronary heart disease

Energy Technology Data Exchange (ETDEWEB)

Buell, U; Strauer, B E; Hast, B; Niendorf, H P [Muenchen Univ. (F.R. Germany). Klinik und Poliklinik fuer Radiologie; Muenchen Univ. (F.R. Germany). 1. Medizinische Klinik)

1976-05-01

/sup 201/Tl scintimetry of the heart was used for a statistical comparison between normal people (10 individuals) and those with acute anterior wall infarcts (5 patients), anterior wall hypokinesia (5 patients) and dyskinesia (8 patients). Numerical results were obtained by a computer and depended on the relative /sup 201/Tl storage in the left ventricular myocardium (64 mm/sup 2/ area) related to mediastinal background uptake. It was found that maximal myocardial uptake, compared with mediastinal activity (about 290%) did not differ between normals and patients with coronary heart disease. Aneurysms of the anterior ventricular wall showed a reduction (with the ventricle perpendicular to the collimator) of 45.8%; in hypokinesia and acute myocardial infarcts, it was 64.2% and 64.6% respectively (normal 82.6%). /sup 201/Tl uptake in aneurysms (42.4%) approached background activity (36%) if a projection parallel to the collimator was used. /sup 201/Tl scintimetry provides a means of defining function ability of the myocardium (depending on myocardial perfusion and mass). Aneurysms and hypokinetic portions of the myocardium can be differentiated statistically from normal /sup 201/Tl uptake.

Assessment of myocardial washout of Tc-99m-sestamibi in patients with chronic heart failure. Comparison with normal control

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Kumita, Shin-ichiro; Seino, Yoshihiko; Cho, Keiichi; Nakajo, Hidenobu; Toba, Masahiro; Fukushima, Yoshimitsu; Takano, Teruo; Kumazaki, Tatsuo [Nippon Medical School, Tokyo (Japan); Okamoto, Noriake [Bristol-Myers Squibb K.K., Tokyo (Japan)

2002-06-01

In contrast to {sup 201}TlCl, {sup 99m}Tc-sestamibi shows very slow myocardial clearance after its initial myocardial uptake. In the present study, myocardial washout of {sup 99m}Tc-sestamibi was calculated in patients with non-ischemic chronic heart failure (CHF) and compared with biventricular parameters obtained from first-pass and ECG-gated myocardial perfusion SPECT data. After administration of {sup 99m}Tc-sestamibi, 25 patients with CHF and 8 normal controls (NC) were examined by ECG-gated myocardial perfusion SPECT and planar data acquisition in the early and delayed (interval of 3 hours) phase. Left ventricular ejection fraction (LVEF, %), peak filling rate (PFR, sec{sup -1}), end-diastolic volume (LVEDV, ml) and end-systolic volume (LVESV, ml) were automatically calculated from the ECG-gated SPECT data. Myocardial washout rates over 3 hours were calculated from the early and delayed planar images. Myocardial washout rates in the CHF group (39.6{+-}5.2%) were significantly higher than those in the NC group (31.2{+-}5.5%, p<0.01). The myocardial washout rates for the 33 subjects showed significant correlations with LVEF (r=-0.61, p<0.001), PFR (r=-0.47, p<0.01), LVEDV (r=0.45, p<0.01) and LVESV (r=0.48, p<0.01). The myocardial washout rate of {sup 99m}Tc-sestamibi is considered to be a novel marker for the diagnosis of myocardial damage in patients with chronic heart failure. (author)

Fibrosis-Related Gene Expression in Single Ventricle Heart Disease.

Science.gov (United States)

Nakano, Stephanie J; Siomos, Austine K; Garcia, Anastacia M; Nguyen, Hieu; SooHoo, Megan; Galambos, Csaba; Nunley, Karin; Stauffer, Brian L; Sucharov, Carmen C; Miyamoto, Shelley D

2017-12-01

To evaluate fibrosis and fibrosis-related gene expression in the myocardium of pediatric subjects with single ventricle with right ventricular failure. Real-time quantitative polymerase chain reaction was performed on explanted right ventricular myocardium of pediatric subjects with single ventricle disease and controls with nonfailing heart disease. Subjects were divided into 3 groups: single ventricle failing (right ventricular failure before or after stage I palliation), single ventricle nonfailing (infants listed for primary transplantation with normal right ventricular function), and stage III (Fontan or right ventricular failure after stage III). To evaluate subjects of similar age and right ventricular volume loading, single ventricle disease with failure was compared with single ventricle without failure and stage III was compared with nonfailing right ventricular disease. Histologic fibrosis was assessed in all hearts. Mann-Whitney tests were performed to identify differences in gene expression. Collagen (Col1α, Col3) expression is decreased in single ventricle congenital heart disease with failure compared with nonfailing single ventricle congenital heart disease (P = .019 and P = .035, respectively), and is equivalent in stage III compared with nonfailing right ventricular heart disease. Tissue inhibitors of metalloproteinase (TIMP-1, TIMP-3, and TIMP-4) are downregulated in stage III compared with nonfailing right ventricular heart disease (P = .0047, P = .013 and P = .013, respectively). Matrix metalloproteinases (MMP-2, MMP-9) are similar between nonfailing single ventricular heart disease and failing single ventricular heart disease, and between stage III heart disease and nonfailing right ventricular heart disease. There is no difference in the prevalence of right ventricular fibrosis by histology in subjects with single ventricular failure heart disease with right ventricular failure (18%) compared with those with normal right

Detection of myocardial 123I-BMIPP distribution abnormality in patients with ischemic heart disease based on normal data file in Bull's-eye polar map

International Nuclear Information System (INIS)

Takahashi, Nobukazu; Ishida, Yoshio; Hirose, Yoshiaki; Kawano, Shigeo; Fukuoka, Syuji; Hayashida, Kohei; Takamiya, Makoto; Nonogi, Hiroshi

1995-01-01

Visual interpretation of 123 I-BMIPP (BMIPP) myocardial images has difficulties in detecting mild reduction in tracer uptake. We studied the significance of the objective assessment of myocardial BMIPP maldistributions at rest by using a Bull's-eye map and its normal data file for detecting ischemic heart disease. Twenty nine patients, 15 with prior myocardial infarction and 14 with effort angina were studied. The initial 15-min BMIPP image was evaluated by visual analysis and by generating the extent Bull's-eye map which exhibits regions with reduced % uptake under mean-2SD of 10 normal controls. The sensitivity for determining coronary lesions in non-infarcted myocardial regions with the extent map was superior to that with visual analysis (67% vs. 33%). In the regions supplied by the stenotic coronary artery, those which showed visually negative but positive in the map and which showed positive in both had higher incidence of wall motion abnormalities and severe coronary stenosis than those with normal findings in both. These results suggest that the objective assessment based on the normal data file in a Bull's-eye polar map is clinically important for improving the limitation or the visual interpretation in 123 I-BMIPP imaging. (author)

Brain natriuretic peptide and right heart dysfunction after heart transplantation.

Science.gov (United States)

Talha, Samy; Charloux, Anne; Piquard, François; Geny, Bernard

2017-06-01

Heart transplantation (HT) should normalize cardiac endocrine function, but brain natriuretic peptide (BNP) levels remain elevated after HT, even in the absence of left ventricular hemodynamic disturbance or allograft rejection. Right ventricle (RV) abnormalities are common in HT recipients (HTx), as a result of engraftment process, tricuspid insufficiency, and/or repeated inflammation due to iterative endomyocardial biopsies. RV function follow-up is vital for patient management as RV dysfunction is a recognized cause of in-hospital death and is responsible for a worse prognosis. Interestingly, few and controversial data are available concerning the relationship between plasma BNP levels and RV functional impairment in HTx. This suggests that infra-clinical modifications, such as subtle immune system disorders or hypoxic conditions, might influence BNP expression. Nevertheless, due to other altered circulating molecular forms of BNP, a lack of specificity of BNP assays is described in heart failure patients. This phenomenon could exist in HT population and could explain elevated BNP plasmatic levels despite a normal RV function. In clinical practice, intra-individual change in BNP over time, rather than absolute BNP values, might be more helpful in detecting right cardiac dysfunction in HTx. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Screening for Coronary Heart Disease with Electrocardiography

Science.gov (United States)

... resting and completely still or while you are exercising. ECG is used to see whether the heart is beating and functioning normally. Potential Benefits and Harms The Task Force reviewed evidence to ...

Evaluation of cimi-shield knock-out bed bug eliminator against house fly (Musca domestica) adults.

Science.gov (United States)

Cimi-Shield Knock-Out (CSKO) Bed Bug Eliminator is a green treatment labeled for use against bed bugs, carpet beetles, ants, roaches, fleas, ticks, silverfish, millipedes and centipedes. The active ingredient is soybean oil. If CSKO is formulated according to label instructions and sprayed directly ...

Knock-in of Enhanced Green Fluorescent Protein or/and Human Fibroblast Growth Factor 2 Gene into β-Casein Gene Locus in the Porcine Fibroblasts to Produce Therapeutic Protein.

Science.gov (United States)

Lee, Sang Mi; Kim, Ji Woo; Jeong, Young-Hee; Kim, Se Eun; Kim, Yeong Ji; Moon, Seung Ju; Lee, Ji-Hye; Kim, Keun-Jung; Kim, Min-Kyu; Kang, Man-Jong

2014-11-01

Transgenic animals have become important tools for the production of therapeutic proteins in the domestic animal. Production efficiencies of transgenic animals by conventional methods as microinjection and retrovirus vector methods are low, and the foreign gene expression levels are also low because of their random integration in the host genome. In this study, we investigated the homologous recombination on the porcine β-casein gene locus using a knock-in vector for the β-casein gene locus. We developed the knock-in vector on the porcine β-casein gene locus and isolated knock-in fibroblast for nuclear transfer. The knock-in vector consisted of the neomycin resistance gene (neo) as a positive selectable marker gene, diphtheria toxin-A gene as negative selection marker, and 5' arm and 3' arm from the porcine β-casein gene. The secretion of enhanced green fluorescent protein (EGFP) was more easily detected in the cell culture media than it was by western blot analysis of cell extract of the HC11 mouse mammary epithelial cells transfected with EGFP knock-in vector. These results indicated that a knock-in system using β-casein gene induced high expression of transgene by the gene regulatory sequence of endogenous β-casein gene. These fibroblasts may be used to produce transgenic pigs for the production of therapeutic proteins via the mammary glands.

Neonate With Severe Heart Failure Related to Vein of Galen Malformation

Directory of Open Access Journals (Sweden)

Meng-Yu Chen

2010-08-01

Full Text Available We report a full-term female neonate who presented with respiratory distress and severe heart failure soon after birth. Heart failure secondary to perinatal infection was initially suspected. Subsequent echocardiography revealed aortic runoff, which led to consideration of an intracranial vascular abnormality. Ultrasound and magnetic resonance imaging of the brain confirmed a diagnosis of vein of Galen aneurismal malformation (VGAM. Endovascular coil embolization of the vascular anomaly was performed, resulting in improvement of heart failure. VGAM should be considered in the differential diagnosis of neonatal congestive heart failure with a structurally normal heart. Urgent endovascular embolization and aggressive medical treatment of heart failure improve prognosis in neonatal VGAM.

[Hypothyroidism in patients with heart disease].

Science.gov (United States)

Jiskra, Jan

Hypothyroidism is frequently found in patients with heart disease. It is a risk factor for atherosclerosis and ischemic heart disease and has a direct negative effect on both the left and right ventricular functions (hypothyroidism-induced cardiomyopathy). The confirmed manifest hypothyroidism is always a reason for replacement therapy with levothyroxine; regarding patients with heart disease, we always begin treatment with a small dose and increase it gradually. The treatment of subclinical hypothyroidism in patients with heart disease is disputable and its benefits probably depend on age. At a higher age, the therapy-related risks often outweigh its benefits, so we make do with the target levels of the thyroid stimulating hormone being within the upper band of the normal range, or even slightly above it, rather than overdosing the patient. To summarize in a simplified way, the treatment of subclinical hypothyroidism in patients with heart disease is the most effective in younger individuals, mainly those aged below 65, while at a higher age > 80 years the risk usually outweighs the benefit.Key words: cardiovascular risk - hypothyroidism - ischemic heart disease - left ventricular dysfunction - right ventricular dysfunction - subclinical hypothyroidism - thyroid peroxidase antibodies.

Heart rate profile during exercise in patients with early repolarization.

Science.gov (United States)

Cay, Serkan; Cagirci, Goksel; Atak, Ramazan; Balbay, Yucel; Demir, Ahmet Duran; Aydogdu, Sinan

2010-09-01

Both early repolarization and altered heart rate profile are associated with sudden death. In this study, we aimed to demonstrate an association between early repolarization and heart rate profile during exercise. A total of 84 subjects were included in the study. Comparable 44 subjects with early repolarization and 40 subjects with normal electrocardiogram underwent exercise stress testing. Resting heart rate, maximum heart rate, heart rate increment and decrement were analyzed. Both groups were comparable for baseline characteristics including resting heart rate. Maximum heart rate, heart rate increment and heart rate decrement of the subjects in early repolarization group had significantly decreased maximum heart rate, heart rate increment and heart rate decrement compared to control group (all P decrement (multiple-adjusted OR of the risk of presence of early repolarization was 2.98 (95%CI 1.21-7.34) (P = 0.018) and 7.73 (95%CI 2.84-21.03) (P decrement compared to higher levels, respectively. Subjects with early repolarization have altered heart rate profile during exercise compared to control subjects. This can be related to sudden death.

Color Doppler Echocardiographic Assessment of Valvular Regurgitation in Normal Infants

Directory of Open Access Journals (Sweden)

Shu-Ting Lee

2010-01-01

Conclusion: The prevalence of inaudible valvular regurgitation is high in infants with structurally normal hearts. Multiple-valve involvement with regurgitation is not uncommon. Mild severity and low velocity on color Doppler, and the structural information provided by 2D imaging strongly suggest that these regurgitant flows are physiologically normal in infancy.

cholesterol, coronary heart disease and oestrogens

African Journals Online (AJOL)

1971-04-03

Apr 3, 1971 ... atheromatosis and coronalY heart disease in the human female are reviewed. Aspects ... For example, Barr' recorded mean levels of 197 in normal women aged 18 ..... Epstein, F. H. (1965): J. Chron. Dis.. 18. 735. 26. Kanne!

Angiocardiography in congenital heart malformations

International Nuclear Information System (INIS)

Soto, B.; Pacifico, A.D.

1990-01-01

The contents of this book are well organized, it deals with the technique of angiocardiography, and describes the angiocardiographic anatomy of the normal heart and offers an excellent sequential analysis of cardiac morphology. The rest of the book describes the angiocardiographic findings observed in individual congenital cardiac disorders

No adaptation to digitalization as evaluated by digitalis receptor (Na,K-ATPase) quantification in explanted hearts from donors without heart disease and from digitalized recipients with end-stage heart failure.

Science.gov (United States)

Schmidt, T A; Allen, P D; Colucci, W S; Marsh, J D; Kjeldsen, K

1993-01-01

Speculations about development of tolerance to the inotropic effect of digitalis have been engendered since studies in various in vitro systems and tissues not representative of the heart have shown up-regulation of sodium potassium adenosine triphosphatase (Na,K-ATPase) when exposed to digitalis. Moreover the digitalis receptor (i.e., Na,K-ATPase) concentration in the normal, vital human left ventricle has not been previously determined. On this basis, digitalis receptor concentration was quantified in the left ventricle of explanted hearts from subjects without heart disease and from patients with end-stage heart failure who had received digitalis therapy. This was performed using vanadate-facilitated 3H-ouabain binding to intact tissue samples giving values of 728 +/- 58 (n = 5) and 467 +/- 55 pmol/g wet weight (n = 6) (mean +/- SEM) (p digitalization was associated with occupancy of digitalis receptors in the failing human heart of 24% (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

ANTXR2 Knock-Out Does Not Result in the Development of Hypertension in Rats.

Science.gov (United States)

Liu, Xiaoyan; Yuan, Wen; Li, Jing; Yang, Lei; Cai, Jun

2017-02-01

Our recent genetic study as well as robust evidences reported by previous genome-wide association studies (GWASs) have indicated that the single nucleotide polymorphism rs16998073, located near gene anthrax toxin receptor 2 (ANTXR2), was significantly associated with hypertension in Asians and Europeans. The aim of the present study was to determine whether ANTXR2 is the causal gene of hypertension at the 4q21 locus using an ANTXR2 knock-out model. Relative expression of ANTXR2 in Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) were determined by real-time quantitative polymerase chain reaction and western blot analysis. ANTXR2 knock-out rats were created using CRISPR/Cas9-mediated genome editing and blood pressure values were measured in ANTXR2 -/- and wild type (WT) rats by tail-cuff method and carotid arterial catheterization method. Neither the mRNA nor protein levels of ANTXR2 were significantly different between tissues from SHRs and WKYs. To create ANTXR2 -/- rats, 67 base pairs were deleted in exon 1 of ANTXR2 using CRISPR/Cas9-mediated genome editing. ANTXR2 protein decreased significantly in aortas of ANTXR2 -/- rats, suggesting sufficient efficiency of ANTXR2 knock-out in this model. However, ANTXR2 -/- rats exhibited nearly the same blood pressure as WT rats at baseline conditions as well as during Angiotensin II (400ng/kg/min) infusion or high-salt diet treatment. These findings suggest that ANTXR2 might not be associated with hypertension and thus further functional analysis is warranted to identify the causal gene at this locus. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants

International Nuclear Information System (INIS)

Glowniak, J.V.; Turner, F.E.; Gray, L.L.; Palac, R.T.; Lagunas-Solar, M.C.; Woodward, W.R.

1989-01-01

Iodine-123 metaiodobenzylguanidine ([ 123 I]MIBG) is a norepinephrine analog which can be used to image the sympathetic innervation of the heart. In this study, cardiac imaging with [ 123 I]MIBG was performed in patients with idiopathic congestive cardiomyopathy and compared to normal controls. Initial uptake, half-time of tracer within the heart, and heart to lung ratios were all significantly reduced in patients compared to normals. Uptake in lungs, liver, salivary glands, and spleen was similar in controls and patients with cardiomyopathy indicating that decreased MIBG uptake was not a generalized abnormality in these patients. Iodine-123 MIBG imaging was also performed in cardiac transplant patients to determine cardiac nonneuronal uptake. Uptake in transplants was less than 10% of normals in the first 2 hr and nearly undetectable after 16 hr. The decreased uptake of MIBG suggests cardiac sympathetic nerve dysfunction while the rapid washout of MIBG from the heart suggests increased cardiac sympathetic nerve activity in idiopathic congestive cardiomyopathy

Selection of reference genes for gene expression studies in heart failure for left and right ventricles.

Science.gov (United States)

Li, Mengmeng; Rao, Man; Chen, Kai; Zhou, Jianye; Song, Jiangping

2017-07-15

Real-time quantitative reverse transcriptase-PCR (qRT-PCR) is a feasible tool for determining gene expression profiles, but the accuracy and reliability of the results depends on the stable expression of selected housekeeping genes in different samples. By far, researches on stable housekeeping genes in human heart failure samples are rare. Moreover the effect of heart failure on the expression of housekeeping genes in right and left ventricles is yet to be studied. Therefore we aim to provide stable housekeeping genes for both ventricles in heart failure and normal heart samples. In this study, we selected seven commonly used housekeeping genes as candidates. By using the qRT-PCR, the expression levels of ACTB, RAB7A, GAPDH, REEP5, RPL5, PSMB4 and VCP in eight heart failure and four normal heart samples were assessed. The stability of candidate housekeeping genes was evaluated by geNorm and Normfinder softwares. GAPDH showed the least variation in all heart samples. Results also indicated the difference of gene expression existed in heart failure left and right ventricles. GAPDH had the highest expression stability in both heart failure and normal heart samples. We also propose using different sets of housekeeping genes for left and right ventricles respectively. The combination of RPL5, GAPDH and PSMB4 is suitable for the right ventricle and the combination of GAPDH, REEP5 and RAB7A is suitable for the left ventricle. Copyright © 2017 Elsevier B.V. All rights reserved.

Introduction to the Congenital Heart Defects: Anatomy of the Conduction System.

Science.gov (United States)

Moore, Jeremy P; Aboulhosn, Jamil A

2017-06-01

The position and course of the conduction system in congenital heart disease are intricately tied to the underlying congenital malformation. Although only subtle differences exist between the anatomy of the conduction axis for simple congenital heart lesions and normal anatomy, almost every patient with congenital heart disease harbors some important anatomic variation. This article summarizes the body of literature by retaining original classical concepts and by attempting to translate the available knowledge into useful points for the congenital heart disease specialist. This discussion spans the entire spectrum of simple to complex congenital heart disease. Copyright © 2017 Elsevier Inc. All rights reserved.

RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing.

Science.gov (United States)

Xie, Zhongcong; Dong, Yuanlin; Maeda, Uta; Xia, Weiming; Tanzi, Rudolph E

2012-03-22

Amyloid-β-protein (Aβ), the key component of senile plaques in Alzheimer's disease (AD) brain, is produced from amyloid precursor protein (APP) by cleavage of β-secretase and then γ-secretase. APP adaptor proteins with phosphotyrosine-binding (PTB) domains, including Dab (gene: DAB) and Numb (gene: NUMB), can bind to and interact with the conserved YENPTY-motif in the APP C-terminus. Here we describe, for the first time, the effects of RNAi knock-down of Dab and Numb expression on APP processing and Aβ production. RNAi knock-down of Dab and Numb in H4 human neuroglioma cells stably transfected to express either FL-APP (H4-FL-APP cells) or APP-C99 (H4-APP-C99 cells) increased levels of APP-C-terminal fragments (APP-CTFs) and lowered Aβ levels in both cell lines by inhibiting γ-secretase cleavage of APP. Finally, RNAi knock-down of APP also reduced levels of Numb in H4-APP cells. These findings suggest that pharmacologically blocking interaction of APP with Dab and Numb may provide novel therapeutic strategies of AD. The notion of attenuating γ-secretase cleavage of APP via the APP adaptor proteins, Dab and Numb, is particularly attractive with regard to therapeutic potential, given that side effects of γ-secretase inhibition owing to impaired proteolysis of other γ-secretase substrates, e.g. Notch, might be avoided.

RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing

Science.gov (United States)

2012-01-01

Amyloid-β-protein (Aβ), the key component of senile plaques in Alzheimer's disease (AD) brain, is produced from amyloid precursor protein (APP) by cleavage of β-secretase and then γ-secretase. APP adaptor proteins with phosphotyrosine-binding (PTB) domains, including Dab (gene: DAB) and Numb (gene: NUMB), can bind to and interact with the conserved YENPTY-motif in the APP C-terminus. Here we describe, for the first time, the effects of RNAi knock-down of Dab and Numb expression on APP processing and Aβ production. RNAi knock-down of Dab and Numb in H4 human neuroglioma cells stably transfected to express either FL-APP (H4-FL-APP cells) or APP-C99 (H4-APP-C99 cells) increased levels of APP-C-terminal fragments (APP-CTFs) and lowered Aβ levels in both cell lines by inhibiting γ-secretase cleavage of APP. Finally, RNAi knock-down of APP also reduced levels of Numb in H4-APP cells. These findings suggest that pharmacologically blocking interaction of APP with Dab and Numb may provide novel therapeutic strategies of AD. The notion of attenuating γ-secretase cleavage of APP via the APP adaptor proteins, Dab and Numb, is particularly attractive with regard to therapeutic potential, given that side effects of γ-secretase inhibition owing to impaired proteolysis of other γ-secretase substrates, e.g. Notch, might be avoided. PMID:23211096

Improved detection of congestive heart failure via probabilistic symbolic pattern recognition and heart rate variability metrics.

Science.gov (United States)

Mahajan, Ruhi; Viangteeravat, Teeradache; Akbilgic, Oguz

2017-12-01

A timely diagnosis of congestive heart failure (CHF) is crucial to evade a life-threatening event. This paper presents a novel probabilistic symbol pattern recognition (PSPR) approach to detect CHF in subjects from their cardiac interbeat (R-R) intervals. PSPR discretizes each continuous R-R interval time series by mapping them onto an eight-symbol alphabet and then models the pattern transition behavior in the symbolic representation of the series. The PSPR-based analysis of the discretized series from 107 subjects (69 normal and 38 CHF subjects) yielded discernible features to distinguish normal subjects and subjects with CHF. In addition to PSPR features, we also extracted features using the time-domain heart rate variability measures such as average and standard deviation of R-R intervals. An ensemble of bagged decision trees was used to classify two groups resulting in a five-fold cross-validation accuracy, specificity, and sensitivity of 98.1%, 100%, and 94.7%, respectively. However, a 20% holdout validation yielded an accuracy, specificity, and sensitivity of 99.5%, 100%, and 98.57%, respectively. Results from this study suggest that features obtained with the combination of PSPR and long-term heart rate variability measures can be used in developing automated CHF diagnosis tools. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of exercise testing in heart failure.

Science.gov (United States)

Swedberg, K; Gundersen, T

1993-01-01

The objectives of exercise testing in congestive heart failure (CHF) may be summarized as follows: (a) detect impaired cardiac performance, (b) grade severity of cardiac failure and classify functional capability, and (c) assess effects of interventions. Several different methods are available to make these assessments, and we have to ask ourselves how well exercise testing achieves these objectives. It has to be kept in mind that the power generated by the exercising muscles is dependent on the oxygen delivery to the skeletal muscles. Oxygen uptake is the result of an integrated performance of the lungs, heart, and peripheral circulation. In patients, as well as in normal subjects, oxygen uptake is related to hemodynamic indices such as cardiac output, stroke volume, or exercise duration when a stepwise regulated maximal exercise protocol is used. However, there are major differences in the concept of a true maximum in normal subjects versus heart failure patients. Fit-normal subjects will achieve a real maximal oxygen uptake, whereas patients may stop testing before a maximum is reached because of symptoms such as dyspnea or leg fatigue. Therefore, it is better if the actual oxygen uptake can be measured. "Peak" rather than true maximal oxygen uptake has been suggested for the classification of the severity of heart failure. Peripheral factors modify the cardiac output through such factors as vascular resistance, organ function, and hormonal release. Maximal exercise will stress the cardiovascular system to a point where the weakest chain will impose a limiting effect.(ABSTRACT TRUNCATED AT 250 WORDS)

The structurally novel Ca2+ channel blocker Ro 40-5967, which binds to the [3H] desmethoxyverapamil receptor, is devoid of the negative inotropic effects of verapamil in normal and failing rat hearts

International Nuclear Information System (INIS)

Clozel, J.P.; Veniant, M.; Osterrieder, W.

1990-01-01

Ro 40-5967 is a structurally novel Ca 2+ channel blocker that binds to the verapamil-type receptor of cardiac membranes but that has been shown in isolated guinea-pig hearts to be about ten times less potent a negative inotropic agent than verapamil. The goals of the present study were to confirm these findings in vitro in isolated perfused rat hearts as well as in vivo in conscious rats and to compare Ro 40-5967 to verapamil. The effects of Ro 40-5967 and verapamil were tested not only in normal rats, but also in rats with heart failure induced by chronic myocardial infarction. In isolated Langendorff hearts (without heart failure), no decrease of contractility was observed with Ro 40-5967 up to complete AV block. In contrast, verapamil decreased contractility with an IC50 of 100 nM. In isolated, electrically stimulated rat papillary muscles, the IC50 values for the decrease of contractile force were 15,000 and 440 nM for Ro 40-5967 and verapamil, respectively. In vivo, Ro 40-5967 did not decrease left ventricular contractility (as assessed by changes of dP/dt max +) in rats without and with heart failure. In contrast, verapamil was markedly negative inotropic in both conditions

FPGA Implementation of Heart Rate Monitoring System.

Science.gov (United States)

Panigrahy, D; Rakshit, M; Sahu, P K

2016-03-01

This paper describes a field programmable gate array (FPGA) implementation of a system that calculates the heart rate from Electrocardiogram (ECG) signal. After heart rate calculation, tachycardia, bradycardia or normal heart rate can easily be detected. ECG is a diagnosis tool routinely used to access the electrical activities and muscular function of the heart. Heart rate is calculated by detecting the R peaks from the ECG signal. To provide a portable and the continuous heart rate monitoring system for patients using ECG, needs a dedicated hardware. FPGA provides easy testability, allows faster implementation and verification option for implementing a new design. We have proposed a five-stage based methodology by using basic VHDL blocks like addition, multiplication and data conversion (real to the fixed point and vice-versa). Our proposed heart rate calculation (R-peak detection) method has been validated, using 48 first channel ECG records of the MIT-BIH arrhythmia database. It shows an accuracy of 99.84%, the sensitivity of 99.94% and the positive predictive value of 99.89%. Our proposed method outperforms other well-known methods in case of pathological ECG signals and successfully implemented in FPGA.

Vertebral scale system to measure heart size in thoracic radiographs ...

African Journals Online (AJOL)

In veterinary diagnostic radiology, determination of heart size is necessary in the assessment of patients with clinical signs of cardiac anomaly. In this study, heart sizes were compared with lengths of mid-thoracic vertebrae in 12 clinically normal West African Dwarf Goats (WADGs) (8 females, 4 males). The aim of the ...

CARDIOTHORACIC RATIO AND VERTEBRAL HEART SCALE IN CLINICALLY NORMAL BLACK-RUMPED AGOUTIS (DASYPROCTA PRYMNOLOPHA, WAGLER 1831).

Science.gov (United States)

de Moura, Charlys Rhands Coelho; das Neves Diniz, Anaemilia; da Silva Moura, Laecio; das Chagas Araújo Sousa, Francisco; Baltazar, Pollyana Irene; Freire, Larisse Danielle; Guerra, Porfírio Candanedo; de Sousa, João Macedo; Giglio, Robson Fortes; Pessoa, Gerson Tavares; de Sá, Renan Paraguassu; Alves, Flávio Ribeiro

2015-06-01

Wild rodents, such as the lowland paca (Cuniculus paca), capybara (Hydrochoerus hydrochaeris), rock cavy (Kerodon rupestris), guinea pig (Cavia aperea), and black-rumped agouti (Dasyprocta prymnolopha) are intensely hunted throughout Amazonia and at the semiarid regions of northeastern Brazil. To contribute to the preservation of these species, more information about their anatomy, physiology and pathophysiology is needed. The aim of this study was to standardize the vertebral heart scale (VHS) and cardiothoracic ratio (CTR) in clinically normal black-rumped agouti, as well as to compare the results of these two methods, which are commonly used to evaluate the cardiac silhouette in domestic animals. Twelve healthy black-rumped agoutis, divided into two groups (six males and six females), obtained from the Nucleus for Wild Animal Studies and Conservation at the Federal University of Piauí, were radiographed in right and left lateral and dorsoventral projections. The values of the VHS were 8.00±0.31v (the number of thoracic vertebral length spanned by each dimension, starting at T4) for males and 8.11±0.41v for females, and there was no statistical difference between the decubitus (right and left) or between males and females (P>0.05). The CTR mean values obtained were 0.51±0.03 for males, and 0.52±0.02 for females, and there was no statistical difference between the genders (P>0.05). However, there was positive correlation between VHS and CTR (r=0.77 right decubitus and r=0.82 left decubitus). The thoracic and heart diameter had mean values of 6.72±0.61 and 3.48±0.30 cm (males), and for the females, it was 6.61±0.51 and 3.5±0.30 cm, respectively, and there was statistical difference between the genders. The results demonstrated high correlation between the VHS and CTR producing similar results, indicating similar clinical precision for assessing the size of the cardiac silhouette in the black-rumped agoutis.

Recruitment of aged donor heart with pharmacological stress echo. A case report

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Bombardini Tonino

2006-01-01

Full Text Available Abstract Background The heart transplant is a treatment of the heart failure, which is not responding to medications, and its efficiency is already proved: unfortunately, organ donation is a limiting step of this life-saving procedure. To counteract heart donor shortage, we should screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease. Donors with a history of cardiac disease are generally excluded. Coronary angiography is recommended for most male donors older than 45 years and female donors older than 50 years to evaluate coronary artery stenoses. A simpler way to screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease should be stress echocardiography. Case report A marginal donor (A 57 year old woman meeting legal requirements for brain death underwent a transesophageal (TE Dipyridamole stress echo (6 minutes accelerated protocol to rule out moderate or severe heart and coronary artery disease. Wall motion was normal at baseline and at peak stress (WMSI = 1 at baseline and peak stress, without signs of stress inducible ischemia. The pressure/volume ratio was 9.6 mmHg/ml/m2 at baseline, increasing to 14 mmHg/ml/m2 at peak stress, demonstrating absence of latent myocardial dysfunction. The marginal donor heart was transplanted to a recipient "marginal" for co-morbidity ( a 63 year old man with multiple myeloma and cardiac amyloidosis , chronic severe heart failure, NYHA class IV. Postoperative treatment and early immunosuppressant regimen were performed according to standard protocols. The transplanted heart was assessed normal for dimensions and ventricular function at transthoracic (TT echocardiography on post-transplant day 7. Coronary artery disease was ruled out at coronary angiography one month after transplant; left ventriculography showed normal global and segmental LV function of the transplanted heart. Conclusion For

Possibility of investigation of pion degrees of freedom in atomic nuclei with the help of quasielastic pions knocking out by high energy electrons

CERN Document Server

Neudachin, V G; Sviridova, L L

2002-01-01

The attention is paid to the interesting possibilities of studying the pion degrees of freedom in the atomic nuclei by means of the quasielastic knocking out of pion (e, ep) from the nuclei by the electrons with the energy of several GeV. It appears, that the pulse distribution of the pions, knocked out from the separate nucleons and the nuclei, is in the whole differ essentially different

Knock-on tail formation due to nuclear elastic scattering and its observation method using γ-ray-generating "6Li+d reaction in tokamak deuterium plasmas

International Nuclear Information System (INIS)

Matsuura, Hideaki; Sugiyama, Shota; Kajimoto, Shogo; Sawada, Daisuke; Nishimura, Yosuke; Kawamoto, Yasuko

2016-01-01

A knock-on tail formation in deuteron velocity distribution function due to nuclear elastic scattering (NES) by energetic protons and its observation method using γ-ray-generating "6Li(d,pγ)"7Li reaction are examined for proton-beam-injected deuterium plasmas. The proton velocity distribution function is obtained by means of the ion trajectory analysis in a Tokamak magnetic configuration. The knock-on tail in two-dimensional (2D) deuteron velocity distribution function due to NES by energetic protons is evaluated via Boltzmann collision integral and 2D Fokker-Planck simulation. From the 2D deuteron velocity distribution function obtained, enhancement of the emission rate of 0.48-MeV γ-rays by "6Li(d,p)"7Li*, "7Li*→"7Li+γ reaction due to NES is evaluated. It is shown that the γ-ray emission rate is significantly influenced by the magnitude of the knock-on tail, and the γ-ray-generating reaction can be a useful tool for the knock-on tail observation. (author)

Activation of PPARγ Ameliorates Spatial Cognitive Deficits through Restoring Expression of AMPA Receptors in Seipin Knock-Out Mice.

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Zhou, Libin; Chen, Tingting; Li, Guoxi; Wu, Chaoming; Wang, Conghui; Li, Lin; Sha, Sha; Chen, Lei; Liu, George; Chen, Ling

2016-01-27

A characteristic phenotype of congenital generalized lipodystrophy 2 (CGL2) that is caused by loss-of-function of seipin gene is mental retardation. Here, we show that seipin deficiency in hippocampal CA1 pyramidal cells caused the reduction of peroxisome proliferator-activated receptor gamma (PPARγ). Twelve-week-old systemic seipin knock-out mice and neuronal seipin knock-out (seipin-nKO) mice, but not adipose seipin knock-out mice, exhibited spatial cognitive deficits as assessed by the Morris water maze and Y-maze, which were ameliorated by the treatment with the PPARγ agonist rosiglitazone (rosi). In addition, seipin-nKO mice showed the synaptic dysfunction and the impairment of NMDA receptor-dependent LTP in hippocampal CA1 regions. The density of AMPA-induced current (IAMPA) in CA1 pyramidal cells and GluR1/GluR2 expression were significantly reduced in seipin-nKO mice, whereas the NMDA-induced current (INMDA) and NR1/NR2 expression were not altered. Rosi treatment in seipin-nKO mice could correct the decrease in expression and activity of AMPA receptor (AMPAR) and was accompanied by recovered synaptic function and LTP induction. Furthermore, hippocampal ERK2 and CREB phosphorylation in seipin-nKO mice were reduced and this could be rescued by rosi treatment. Rosi treatment in seipin-nKO mice elevated BDNF concentration. The MEK inhibitor U0126 blocked rosi-restored AMPAR expression and LTP induction in seipin-nKO mice, but the Trk family inhibitor K252a did not. These findings indicate that the neuronal seipin deficiency selectively suppresses AMPAR expression through reducing ERK-CREB activities, leading to the impairment of LTP and spatial memory, which can be rescued by PPARγ activation. Congenital generalized lipodystrophy 2 (CGL2), caused by loss-of-function mutation of seipin gene, is characterized by mental retardation. By the generation of systemic or neuronal seipin knock-out mice, the present study provides in vivo evidence that neuronal seipin

Validity of (Ultra-)Short Recordings for Heart Rate Variability Measurements

NARCIS (Netherlands)

Muñoz Venegas, Loretto; van Roon, Arie; Riese, Harriette; Thio, Chris; Oostenbroek, Emma; Westrik, Iris; de Geus, Eco J. C.; Gansevoort, Ron; Lefrandt, Joop; Nolte, Ilja M.; Snieder, Harold

2015-01-01

Objectives In order to investigate the applicability of routine 10s electrocardiogram (ECG) recordings for time-domain heart rate variability (HRV) calculation we explored to what extent these (ultra-)short recordings capture the "actual" HRV. Methods The standard deviation of normal-to-normal

Physiological roles of the transient outward current Ito in normal and diseased hearts

DEFF Research Database (Denmark)

Cordeiro, Jonathan M.; Callø, Kirstine; Aschar-Sobbi, Roozbeh

2016-01-01

The Ca2+-independent transient outward K+ current (Ito) plays a critical role in underlying phase 1 of repolarization of the cardiac action potential and, as a result, is central to modulating excitation-contraction coupling and propensity for arrhythmia. Additionally, Ito and its molecular...... potential and the mechanisms by which Ito modulates excitation-contraction coupling. We also describe the effects of mutations in the subunits constituting the Ito channel as well as the role of Ito in the failing myocardium. Finally, we review pharmacological modulation of Ito and discuss the evidence...... constituents are consistently reduced in cardiac hypertrophy and heart failure. In this review, we discuss the physiological role of Ito as well as the molecular basis of this current in human and canine hearts, in which Ito has been thoroughly studied. In particular, we discuss the role of Ito in the action...

Evaluation of multi-gated myocardial perfusion imaging in various heart diseases

International Nuclear Information System (INIS)

Nishimura, Tsunehiko; Uehara, Toshitake; Kozuka, Takahiro

1980-01-01

Multi-gated myocardial perfusion imaging were studied in a hundred cases of various heart diseases. In normal cases, ED ES images showed thinning and thickening of wall motion respectively to compare with static images. In the myocardial infarction cases, the dynamic changes of wall motion was decreased at infarcted areas in all cases. In congestive cardiomyopathy, the change of wall motion is smaller than normal cases in all cases, while in hypertrophic cardiomyopathy, the change is not so hyperdynamic to compare with normal cases and by multi-gated images, asymmetric hypertrophy was clearly detected in HCM than static images. In conclusion, these methods were useful to detect the myocardial contraction stage in various heart diseases. (author)

Practical method for targeted disruption of cilia-related genes by using CRISPR/Cas9-mediated, homology-independent knock-in system.

Science.gov (United States)

Katoh, Yohei; Michisaka, Saki; Nozaki, Shohei; Funabashi, Teruki; Hirano, Tomoaki; Takei, Ryota; Nakayama, Kazuhisa

2017-04-01

The CRISPR/Cas9 system has revolutionized genome editing in virtually all organisms. Although the CRISPR/Cas9 system enables the targeted cleavage of genomic DNA, its use for gene knock-in remains challenging because levels of homologous recombination activity vary among various cells. In contrast, the efficiency of homology-independent DNA repair is relatively high in most cell types. Therefore the use of a homology-independent repair mechanism is a possible alternative for efficient genome editing. Here we constructed a donor knock-in vector optimized for the CRISPR/Cas9 system and developed a practical system that enables efficient disruption of target genes by exploiting homology-independent repair. Using this practical knock-in system, we successfully disrupted genes encoding proteins involved in ciliary protein trafficking, including IFT88 and IFT20, in hTERT-RPE1 cells, which have low homologous recombination activity. The most critical concern using the CRISPR/Cas9 system is off-target cleavage. To reduce the off-target cleavage frequency and increase the versatility of our knock-in system, we constructed a universal donor vector and an expression vector containing Cas9 with enhanced specificity and tandem sgRNA expression cassettes. We demonstrated that the second version of our system has improved usability. © 2017 Katoh et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Association of elevated serum cardiac troponin-I level and complications in acute heart failurecases

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Farjana Akhter

2013-07-01

Full Text Available Acute heart failure is one of the major causes of morbidity and mortality all over the world. Available published data has suggested that patients of acute heart failure with elevated level of serum cardiac troponin-I (cTn-I have more adverse outcomes than that of acute heart failure with normal cTn-I level. Elevated level of serum cTn-I is a potential risk factor for acute heart failure. This study was carried out in the department of Biochemistry, Dhaka Medical College and National Institute of Cardiovascular Disease (NICVD during the period from January 2010 to December 2010. In this study, 100 patients with acute heart failure were enrolled. Out of 100 cases, 50 had elevated serum cTn-I (cTn-I ³ 1.0 ng/ml and 50 had normal serum cTn-I (cTn-I < 1.0 ng/ml. The adverse outcome of the two groups were recorded and compared. Patients with high and normal serum cTn-I had mean age of 52.40 ± 8.10 years and 54.64 ± 7.26 years respectively while male and female cases were equally distributed. Left ventricular systolic dysfunction (lower ejection fraction was significantly (p<0.05 higher among cases with elevated cTn-I level compared to those with normal level. The rate of renal failure (raised serum creatinine, impaired liver functions (raised ALT and AST and abnormal serum electrolytes were significantly higher among the patients with elevated cTn-I compared to those with normal level. The study showed that elevated serum cTn-I level was a good biomarker to indicate adverse complications in acute heart failure cases. Ibrahim Med. Coll. J. 2013; 7(2: 32-34

Reduced expression of mitochondrial electron transport chain proteins from hibernating hearts relative to ischemic preconditioned hearts in the second window of protection.

Science.gov (United States)

Cabrera, Jesús A; Butterick, Tammy A; Long, Eric K; Ziemba, Elizabeth A; Anderson, Lorraine B; Duffy, Cayla M; Sluiter, Willem; Duncker, Dirk J; Zhang, Jianyi; Chen, Yingjie; Ward, Herbert B; Kelly, Rosemary F; McFalls, Edward O

2013-07-01

Although protection against necrosis has been observed in both hibernating (HIB) and ischemic preconditioned hearts in the second window of protection (SWOP), a comparison of the mitochondrial proteome between the two entities has not been previously performed. Anesthetized swine underwent instrumentation with a fixed constrictor around the LAD artery and were followed for 12 weeks (HIB; N=7). A second group of anesthetized swine underwent ischemic preconditioning by inflating a balloon within the LAD artery 10 times for 2 min, each separated by 2 min reperfusion and were sacrificed 24h later (SWOP; N=7). Myocardial blood flow and high-energy nucleotides were obtained in the LAD region and normalized to remote regions. Post-sacrifice, protein content as measured with iTRAQ was compared in isolated mitochondria from the LAD area of a Sham heart. Basal regional blood flow in the LAD region when normalized to the remote region was 0.86±0.04 in HIB and 1.02±0.02 in SWOP tissue (Pregional blood flows in HIB hearts, ATP content in the LAD region, when normalized to the remote region was similar in HIB versus SWOP (1.06±0.06 and 1.02±0.05 respectively; NS) as was the transmural phosphocreatine (PCr) to ATP ratio (2.1±0.2 and 2.2±0.2 respectively; NS). Using iTRAQ, 64 common proteins were identified in HIB and SWOP hearts. Compared with SWOP, the relative abundance of mitochondrial proteins involved with electron transport chain (ETC) were reduced in HIB including NADH dehydrogenase, Cytochrome c reductase and oxidase, ATP synthase, and nicotinamide nucleotide transhydrogenase. Within chronically HIB heart tissue with reduced blood flow, the relative abundance of mitochondrial ETC proteins is decreased when compared with SWOP tissue. These data support the concept that HIB heart tissue subjected to chronically reduced blood flow is associated with a down-regulation in the expression of key mitochondrial proteins involved in electron transport. Published by Elsevier

Variable laterality of corticospinal tract axons that regenerate after spinal cord injury as a result of PTEN deletion or knock-down

Science.gov (United States)

Willenberg, Rafer; Zukor, Katherine; Liu, Kai; He, Zhigang; Steward, Oswald

2016-01-01

Corticospinal tract (CST) axons from one hemisphere normally extend and terminate predominantly in the contralateral spinal cord. We previously showed that deleting PTEN in the sensorimotor cortex enables CST axons to regenerate after spinal cord injury and that some regenerating axons extend along the “wrong” side. Here, we characterize the degree of specificity of regrowth in terms of laterality. PTEN was selectively deleted via cortical AAV-Cre injections in neonatal PTEN-floxed mice. As adults, mice received dorsal hemisection injuries at T12 or complete crush injuries at T9. CST axons from one hemisphere were traced by unilateral BDA injections in PTEN-deleted mice with spinal cord injury and in non-injured PTEN-floxed mice that had not received AAV-Cre. In non-injured mice, 97.9 ± 0.7% of BDA-labeled axons in white matter and 88.5 ± 1.0% of BDA-labeled axons in grey matter were contralateral to the cortex of origin. In contrast, laterality of CST axons that extended past a lesion due to PTEN deletion varied across animals. In some cases, regenerated axons extended predominantly on the ipsilateral side, in other cases, axons extended predominantly contralaterally, and in others, axons were similar in numbers on both sides. Similar results were seen in analyses of cases from previous studies using shRNA-mediated PTEN knock-down. These results indicate that CST axons that extend past a lesion due to PTEN deletion or knock-down do not maintain the contralateral rule of the non-injured CST, highlighting one aspect for how resultant circuitry from regenerating axons may differ from that of the uninjured CST. PMID:26878190

Complete heart block in a patient with POEMS syndrome: A case report

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Farzaneh Ashrafi

2014-09-01

Full Text Available BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, monoclonal syndrome (POEMS is a rare paraneoplastic syndrome associated with plasma cell dyscrasia. CASE REPORT: A 48-year-old man presented with a 1-year history of paresthesia and progressive weakness of extremities. Diagnosis of POEMS syndrome was made for him on the basis of clinical presentation, additional physical findings, typical sclerotic bone lesion, and bone marrow findings. In last admission, he explained episodes of dyspnea and chest pain that associated with frequent premature ventricular contraction in his electrocardiograph. Patient heart monitoring showed some episodes of complete heart block. Infra-His atrioventricular block in electro-physiologic study was detected. He had no history of ischemic heart disease. His cardiopulmonary findings on examination were normal. All results of cardiac biomarkers and serum electrolytes and repeated echocardiography were within normal range. Cong red staining of rectal fat pad biopsy was negative. After pacemaker insertion radiation of sclerotic bone, lesion started for him, but radiotherapy was ineffective, and he expired with respiratory failure. Complete heart block in POEMS syndrome has not been reported previously, and it is the first POEMS case with complete heart block. CONCLUSION: Complete heart block is a cardiac manifestation of POEMS syndrome.   Keywords: Complete Heart Block, POEM Syndrome, Multiple Meloma 

Changes of plasma neuropeptide Y levels in patients with ischemic heart disease

International Nuclear Information System (INIS)

Cheng Guanghua; Zhang Xinlu; Yang Jun

2001-01-01

Objective: To study the pathophysiological significance of neuropeptide Y(NPY) in ischemic heart disease (IHD). Methods: The plasma NPY levels were measured by radioimmunoassay in 35 patients with angina pectoris (Group A), 31 patients with acute myocardial infarctions (AMI) without heart failure (Group B), 29 patients of AMI with left heart failure (Group C) and 27 normal subjects. Results: The plasma NPY levels were higher in all these patients on admission than those in controls with the highest values in the most severe patients. The NPY levels in group A decreased to normal levels on day 1. In group B a significant increase in the levels of NPY was observed on day 1. Their NPY levels decreased significantly on days 4 and 7, but never to normal levels until day 28. Considerable increase in the levels of NPY were observed in group C on days 1 and 4. The levels of NPY were extremely high in six AMI patients with acute left heart failure before death. The NPY levels began to decrease on day 7 but never to their levels on admission until day 28; at that time the NPY levels were still higher than those in controls. Conclusion: These information indicated that plasma NPY might be useful for monitoring and predicting prognosis in patients with ischemic heart disease

Energy spectra of primary knock-on atoms under neutron irradiation

International Nuclear Information System (INIS)

Gilbert, M.R.; Marian, J.; Sublet, J.-Ch.

2015-01-01

Materials subjected to neutron irradiation will suffer from a build-up of damage caused by the displacement cascades initiated by nuclear reactions. Previously, the main “measure” of this damage accumulation has been through the displacements per atom (dpa) index, which has known limitations. This paper describes a rigorous methodology to calculate the primary atomic recoil events (often called the primary knock-on atoms or PKAs) that lead to cascade damage events as a function of energy and recoiling species. A new processing code SPECTRA-PKA combines a neutron irradiation spectrum with nuclear recoil data obtained from the latest nuclear data libraries to produce PKA spectra for any material composition. Via examples of fusion relevant materials, it is shown that these PKA spectra can be complex, involving many different recoiling species, potentially differing in both proton and neutron number from the original target nuclei, including high energy recoils of light emitted particles such as α-particles and protons. The variations in PKA spectra as a function of time, neutron field, and material are explored. The application of PKA spectra to the quantification of radiation damage is exemplified using two approaches: the binary collision approximation and stochastic cluster dynamics, and the results from these different models are discussed and compared. - Highlights: • Recoil cross-section matrices under neutron irradiation are generated. • Primary knock-on atoms (PKA) spectra are calculated for fusion relevant materials. • Variation in PKA spectra due to changes in geometry are considered. • Inventory simulations to consider time-evolution in PKA spectra. • Damage quantification using damage functions from different approximations.

Structural and functional changes of the heart in patients with chronic ischemic heart failure, associated with renal dysfunction

Directory of Open Access Journals (Sweden)

D. A. Lashkul

2014-04-01

Full Text Available Kidney disease is a frequent complication of congestive heart failure (CHF and may contribute to the progression of ventricular dysfunction. Regardless of the degree of heart failure, chronic kidney disease (CKD increases the risk of death and cardiac decompensation. Left ventricular hypertrophy (LVH is a known parameter of cardiac remodelling and has a higher prevalence and incidence among people with impaired kidney function. LVH is an early subclinical marker of cardiovascular disease and heart failure risk, and is probably an intermediary step in the pathway leading from kidney dysfunction to heart failure and its complications. The effects of CKD on other left ventricular and myocardial parameters, however, have been less characterized. The aim of the study was to examine the structural and functional changes, geometric remodeling of the heart in patients with ischemic chronic heart failure, being hospitalized, according to the presence of renal dysfunction. Materials and methods. The study involved 333 patients with ischemic CHF (277 men and 56 women, mean age 59,3±9,4 years. The functional class of heart failure was assessed on the recommendations of the New York Heart Association (NYHA. The etiology of heart failure in 288 (86.5% patients had a combination of coronary artery disease and essential hypertension, in 45 (13.5% – only CAD. 1 FC of heart failure was diagnosed in 9 (2.7% patients, 2 FC - in 106 (31.8%, 3 FC - in 199 (59.8% and 4 FC - 19 (5.7% patients. Diabetes was in 61 (18.3%, myocardial infarction history was in 240 (72.1% patients. Depending on the glomerular filtration rate, patients were divided into 3 groups: 72 with normal GFR (>90 ml/min/1.73m2, 218 with a slight decrease in GFR (60-90 ml/min/1.73m2 and 43 with moderate reduced GFR (<60 ml/min/1.73m2. Echocardiography was performed using the General Electric VIVID 3 system (General Electric Healthcare, USA with the 2.5–3.5 MHz transducer and Doppler technique

[Expression of proBNP and NT-proBNP in Sudden Death of Coronary Heart Disease].

Science.gov (United States)

Zeng, Q; Sun, R F; Li, Z; Zhai, L Q; Liu, M Z; Guo, X J; Gao, C R

2017-10-01

To study the expression change of pro-brain natriuretic peptide （proBNP） and N-terminal pro-brain natriuretic peptide （NT-proBNP） in sudden death of coronary atherosclerotic heart disease, and to explore its application in forensic diagnosis. Myocardial and blood samples were collected from normal control group, sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group （20 cases in each group）. The expression of proBNP in myocardial samples were detected by immunohistochemical staining and Western blotting, and that of BNP mRNA were detected by reverse transcription PCR （RT-PCR）. The content of NT-proBNP in plasma were detected by ELISA. Immunohistochemical staining showed positive expression of proBNP in both sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group. There was no positive expression in normal control group. For sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group, the relative expression of proBNP protein and BNP mRNA in myocardial tissue and the NT-proBNP content in plasma were higher than that of normal control group （ P heart disease group was higher than that of single coronary stenosis group （ P heart disease and determine whether the sudden death due to coronary atherosclerotic heart disease. Copyright© by the Editorial Department of Journal of Forensic Medicine

Fast and efficient Drosophila melanogaster gene knock-ins using MiMIC transposons.

Science.gov (United States)

Vilain, Sven; Vanhauwaert, Roeland; Maes, Ine; Schoovaerts, Nils; Zhou, Lujia; Soukup, Sandra; da Cunha, Raquel; Lauwers, Elsa; Fiers, Mark; Verstreken, Patrik

2014-10-08

Modern molecular genetics studies necessitate the manipulation of genes in their endogenous locus, but most of the current methodologies require an inefficient donor-dependent homologous recombination step to locally modify the genome. Here we describe a methodology to efficiently generate Drosophila knock-in alleles by capitalizing on the availability of numerous genomic MiMIC transposon insertions carrying recombinogenic attP sites. Our methodology entails the efficient PhiC31-mediated integration of a recombination cassette flanked by unique I-SceI and/or I-CreI restriction enzyme sites into an attP-site. These restriction enzyme sites allow for double-strand break-mediated removal of unwanted flanking transposon sequences, while leaving the desired genomic modifications or recombination cassettes. As a proof-of-principle, we mutated LRRK, tau, and sky by using different MiMIC elements. We replaced 6 kb of genomic DNA encompassing the tau locus and 35 kb encompassing the sky locus with a recombination cassette that permits easy integration of DNA at these loci and we also generated a functional LRRK(HA) knock in allele. Given that ~92% of the Drosophila genes are located within the vicinity (MiMIC element, our methodology enables the efficient manipulation of nearly every locus in the fruit fly genome without the need for inefficient donor-dependent homologous recombination events. Copyright © 2014 Vilain et al.

Targeted knock-in of an scFv-Fc antibody gene into the hprt locus of Chinese hamster ovary cells using CRISPR/Cas9 and CRIS-PITCh systems.

Science.gov (United States)

Kawabe, Yoshinori; Komatsu, Shinya; Komatsu, Shodai; Murakami, Mai; Ito, Akira; Sakuma, Tetsushi; Nakamura, Takahiro; Yamamoto, Takashi; Kamihira, Masamichi

2018-05-01

Chinese hamster ovary (CHO) cells have been used as host cells for the production of pharmaceutical proteins. For the high and stable production of target proteins, the transgene should be integrated into a suitable genomic locus of host cells. Here, we generated knock-in CHO cells, in which transgene cassettes without a vector backbone sequence were integrated into the hprt locus of the CHO genome using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and CRISPR-mediated precise integration into target chromosome (CRIS-PITCh) systems. We investigated the efficiency of targeted knock-in of transgenes using these systems. As a practical example, we generated knock-in CHO cells producing an scFv-Fc antibody using the CRIS-PITCh system mediated by microhomology sequences for targeting. We found that the CRIS-PITCh system can facilitate targeted knock-in for CHO cell engineering. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Chaos control applied to heart rhythm dynamics

Energy Technology Data Exchange (ETDEWEB)

Borem Ferreira, Bianca, E-mail: biaborem@gmail.com [Universidade Federal do Rio de Janeiro, COPPE, Department of Mechanical Engineering, P.O. Box 68.503, 21.941.972 Rio de Janeiro, RJ (Brazil); Souza de Paula, Aline, E-mail: alinedepaula@unb.br [Universidade de Brasi' lia, Department of Mechanical Engineering, 70.910.900 Brasilia, DF (Brazil); Amorim Savi, Marcelo, E-mail: savi@mecanica.ufrj.br [Universidade Federal do Rio de Janeiro, COPPE, Department of Mechanical Engineering, P.O. Box 68.503, 21.941.972 Rio de Janeiro, RJ (Brazil)

2011-08-15

Highlights: > A natural cardiac pacemaker is modeled by a modified Van der Pol oscillator. > Responses related to normal and chaotic, pathological functioning of the heart are investigated. > Chaos control methods are applied to avoid pathological behaviors of heart dynamics. > Different approaches are treated: stabilization of unstable periodic orbits and chaos suppression. - Abstract: The dynamics of cardiovascular rhythms have been widely studied due to the key aspects of the heart in the physiology of living beings. Cardiac rhythms can be either periodic or chaotic, being respectively related to normal and pathological physiological functioning. In this regard, chaos control methods may be useful to promote the stabilization of unstable periodic orbits using small perturbations. In this article, the extended time-delayed feedback control method is applied to a natural cardiac pacemaker described by a mathematical model. The model consists of a modified Van der Pol equation that reproduces the behavior of this pacemaker. Results show the ability of the chaos control strategy to control the system response performing either the stabilization of unstable periodic orbits or the suppression of chaotic response, avoiding behaviors associated with critical cardiac pathologies.

Cine-MR imaging of valvular heart disease

International Nuclear Information System (INIS)

Park, Jae Hyung; Han, Man Chung; Kim, Chu Wan; Kim, Dae Jin; Kim, Woo Sung; Park, Hyun Wuk; Cho, Zang Hee

1989-01-01

Cine-MR imaging was done in 2 normal persons and 9 patients of valvular heart disease with 2.0 T superconducting MR system (Spectro-2000; GoldStar, Korea). The MRI was undertaken using gradient echo technique with small flip angle. Repetition time (TR) was 34 msec, and echo time (TE), 18 msec. In most cases, 20 to 30 frames could be obtained during one cardiac cycle. With normal heart, high signal intensity was identified in the blood filled cardiac chambers. Transient signal void was observed near tricuspid, mitral and aortic valves due to the turbulences induced by valve opening or closure. In 6 cases of mitral valvular disease, mitral valve was identified in all cases. The valvular motion was limited revealing doming toward cardiac apex during diastole. Signal void was evident in pansystolic phase of left ventricle in all cases. Evidence of combined aortic or tricuspid valve disease were also demonstrated, revealing signal void in the corresponding cardiac chambers. Cine-MRI seemed to be not only a good non-invasive diagnostic modality for the valvular heart disease, but also an accurate modality for cardiac functional evaluation

Cine-MR imaging of valvular heart disease

Energy Technology Data Exchange (ETDEWEB)

Park, Jae Hyung; Han, Man Chung; Kim, Chu Wan [Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Dae Jin; Kim, Woo Sung; Park, Hyun Wuk; Cho, Zang Hee [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

1989-04-15

Cine-MR imaging was done in 2 normal persons and 9 patients of valvular heart disease with 2.0 T superconducting MR system (Spectro-2000; GoldStar, Korea). The MRI was undertaken using gradient echo technique with small flip angle. Repetition time (TR) was 34 msec, and echo time (TE), 18 msec. In most cases, 20 to 30 frames could be obtained during one cardiac cycle. With normal heart, high signal intensity was identified in the blood filled cardiac chambers. Transient signal void was observed near tricuspid, mitral and aortic valves due to the turbulences induced by valve opening or closure. In 6 cases of mitral valvular disease, mitral valve was identified in all cases. The valvular motion was limited revealing doming toward cardiac apex during diastole. Signal void was evident in pansystolic phase of left ventricle in all cases. Evidence of combined aortic or tricuspid valve disease were also demonstrated, revealing signal void in the corresponding cardiac chambers. Cine-MRI seemed to be not only a good non-invasive diagnostic modality for the valvular heart disease, but also an accurate modality for cardiac functional evaluation.

Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

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Xiaolin He

Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

Creation of knock out and knock in mice by CRISPR/Cas9 to validate candidate genes for human male infertility, interest, difficulties and feasibility.

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Kherraf, Zine-Eddine; Conne, Beatrice; Amiri-Yekta, Amir; Kent, Marie Christou; Coutton, Charles; Escoffier, Jessica; Nef, Serge; Arnoult, Christophe; Ray, Pierre F

2018-06-15

High throughput sequencing (HTS) and CRISPR/Cas9 are two recent technologies that are currently revolutionizing biological and clinical research. Both techniques are complementary as HTS permits to identify new genetic variants and genes involved in various pathologies and CRISPR/Cas9 permits to create animals or cell models to validate the effect of the identified variants, to characterize the pathogeny of the identified variants and the function of the genes of interest and ultimately to provide ways of correcting the molecular defects. We analyzed a cohort of 78 infertile men presenting with multiple morphological anomalies of the sperm flagella (MMAF), a severe form of male infertility. Using whole exome sequencing (WES), homozygous mutations in autosomal candidate genes were identified in 63% of the tested subjects. We decided to produce by CRISPR/cas9 four knock-out (KO) and one knock-in (KI) mouse lines to confirm these results and to increase our understanding of the physiopathology associated with these genetic variations. Overall 31% of the live pups obtained presented a mutational event in one of the targeted regions. All identified events were insertions or deletions localized near the PAM sequence. Surprisingly we observed a high rate of germline mosaicism as 30% of the F1 displayed a different mutation than the parental event characterized on somatic tissue (tail), indicating that CRISPR/Cas9 mutational events kept happening several cell divisions after the injection. Overall, we created mouse models for 5 distinct loci and in each case homozygous animals could be obtained in approximately 6 months. These results demonstrate that the combined use of WES and CRISPR/Cas9 is an efficient and timely strategy to identify and validate mutations responsible for infertility phenotypes in human. Copyright © 2018 Elsevier B.V. All rights reserved.

The clinical importance of radiological determination of the heart volume

International Nuclear Information System (INIS)

Jaedicke, W.; Ong, T.S.; Barmeyer, J.

1982-01-01

The size of the heart is an autonomous, important parameter of its functional state, i.e. in the radiologic heart diagnostics, the measurement of the heart volume is of equal value as the shape analysis. A size determination which must be exact enough for course controls and differentiation from the normal picture makes sense only if the measurement is carriet out in 3 dimensions and not in only one as is done when determining the heart-lung-quotient. The heart volume measurement carried out in lying or sitting position is considerably more reliable than in standing position as too many extracardiac factors influence the heart volume when the patient is standing. The echo cardiogram is a nearly ideal supplement but no competitor of radiological heart volume measurement and can be of the same value as or superior to heart volume measurement for functional diagnostics only in diseases limited to nearly exclusively to the left ventricle as in coronary diseases. (orig.) [de

The mitochondrial uniporter controls fight or flight heart rate increases.

Science.gov (United States)

Wu, Yuejin; Rasmussen, Tyler P; Koval, Olha M; Joiner, Mei-Ling A; Hall, Duane D; Chen, Biyi; Luczak, Elizabeth D; Wang, Qiongling; Rokita, Adam G; Wehrens, Xander H T; Song, Long-Sheng; Anderson, Mark E

2015-01-20

Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart rate increases are resistant to current therapies. However, the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix to stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of a dominant-negative (DN) MCU. Here, we show that DN-MCU mice had normal resting heart rates but were incapable of physiological fight or flight heart rate acceleration. We found that MCU function was essential for rapidly increasing mitochondrial calcium in pacemaker cells and that MCU-enhanced oxidative phoshorylation was required to accelerate reloading of an intracellular calcium compartment before each heartbeat. Our findings show that MCU is necessary for complete physiological heart rate acceleration and suggest that MCU inhibition could reduce inappropriate heart rate increases without affecting resting heart rate.

RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing

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Xie Zhongcong

2012-03-01

Full Text Available Abstract Amyloid-β-protein (Aβ, the key component of senile plaques in Alzheimer's disease (AD brain, is produced from amyloid precursor protein (APP by cleavage of β-secretase and then γ-secretase. APP adaptor proteins with phosphotyrosine-binding (PTB domains, including Dab (gene: DAB and Numb (gene: NUMB, can bind to and interact with the conserved YENPTY-motif in the APP C-terminus. Here we describe, for the first time, the effects of RNAi knock-down of Dab and Numb expression on APP processing and Aβ production. RNAi knock-down of Dab and Numb in H4 human neuroglioma cells stably transfected to express either FL-APP (H4-FL-APP cells or APP-C99 (H4-APP-C99 cells increased levels of APP-C-terminal fragments (APP-CTFs and lowered Aβ levels in both cell lines by inhibiting γ-secretase cleavage of APP. Finally, RNAi knock-down of APP also reduced levels of Numb in H4-APP cells. These findings suggest that pharmacologically blocking interaction of APP with Dab and Numb may provide novel therapeutic strategies of AD. The notion of attenuating γ-secretase cleavage of APP via the APP adaptor proteins, Dab and Numb, is particularly attractive with regard to therapeutic potential, given that side effects of γ-secretase inhibition owing to impaired proteolysis of other γ-secretase substrates, e.g. Notch, might be avoided.

Knock-down and speed of kill of a combination of fipronil and permethrin for the prevention of Ctenocephalides felis flea infestation in dogs.

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Halos, Lénaïg; Fourie, Josephus J; Fankhauser, Becky; Beugnet, Frederic

2016-02-02

A topical combination of fipronil + permethrin (Frontline Tri-Act/Frontect, Merial) has recently been developed to control fleas, ticks, mosquitoes, sandflies and stable flies on dogs. Two studies were conducted to assess its speed of kill and knock-down effect on Ctenocephalides felis fleas. The combination was compared to either fipronil alone or to a combination of permethrin, dinotefuran, and pyriproxyfen, In each study, 18 dogs were randomly allocated to one of three groups: (Group 1: untreated dog; Group 2: treated once on D0 with the combination of fipronil and permethrin; Group 3: treated once on D0 either with fipronil alone (study 1) or with a combination of permethrin, dinetofuran and pyriproxyfen (study 2)). Each dog was infested with 100 unfed adult C. felis fleas on Days 2 (study 2), 7, 14, 21 and 28. Fleas were collected from dogs at 1 h and 12 h post- infestations (PI) (study 1) or at 2 h and 6 h PI (study 2) to assess efficacy and from collection pans underneath cages 1 h (study 1) or 5 min (study 2) PI to assess knock-down effect. All treated dogs had significantly (p ≤ 0.01) lower flea counts than untreated dogs at every time point in both studies. For a whole month, a significant knock-down effect against infesting fleas is obtained in five minutes PI with the combination of permethrin and fipronil. Complete efficacy (>95%) was achieved in 1 h (study 1) or 2 h (study 2) PI for 14 days and by 6 h PI for all challenges conducted throughout the month. Efficacy remains >85% at 2 h PI for the whole month. A significantly higher efficacy of the fipronil + permethrin combination compared to other treatments was demonstrated at the earliest time points for the month (1 h knock-down effect and insecticidal efficacy compared to fipronil alone; 5 min knock-down effect compared to the combination of permethrin + dinetofuran + pyriproxyfen). The rapid flea knock-down effect and speed of kill demonstrated by the spot on combination of

Als2 mRNA splicing variants detected in KO mice rescue severe motor dysfunction phenotype in Als2 knock-down zebrafish.

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Gros-Louis, Francois; Kriz, Jasna; Kabashi, Edor; McDearmid, Jonathan; Millecamps, Stéphanie; Urushitani, Makoto; Lin, Li; Dion, Patrick; Zhu, Qinzhang; Drapeau, Pierre; Julien, Jean-Pierre; Rouleau, Guy A

2008-09-01

Recessive ALS2 mutations are linked to three related but slightly different neurodegenerative disorders: amyotrophic lateral sclerosis, hereditary spastic paraplegia and primary lateral sclerosis. To investigate the function of the ALS2 encoded protein, we generated Als2 knock-out (KO) mice and zAls2 knock-down zebrafish. The Als2(-/-) mice lacking exon 2 and part of exon 3 developed mild signs of neurodegeneration compatible with axonal transport deficiency. In contrast, zAls2 knock-down zebrafish had severe developmental abnormalities, swimming deficits and motor neuron perturbation. We identified, by RT-PCR, northern and western blotting novel Als2 transcripts in mouse central nervous system. These Als2 transcripts were present in Als2 null mice as well as in wild-type littermates and some rescued the zebrafish phenotype. Thus, we speculate that the newly identified Als2 mRNA species prevent the Als2 KO mice from developing severe neurodegenerative disease and might also regulate the severity of the motor neurons phenotype observed in ALS2 patients.

Features of Heart Rate Variability Capture Regulatory Changes During Kangaroo Care in Preterm Infants.

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Kommers, Deedee R; Joshi, Rohan; van Pul, Carola; Atallah, Louis; Feijs, Loe; Oei, Guid; Bambang Oetomo, Sidarto; Andriessen, Peter

2017-03-01

To determine whether heart rate variability (HRV) can serve as a surrogate measure to track regulatory changes during kangaroo care, a period of parental coregulation distinct from regulation within the incubator. Nurses annotated the starting and ending times of kangaroo care for 3 months. The pre-kangaroo care, during-kangaroo care, and post-kangaroo care data were retrieved in infants with at least 10 accurately annotated kangaroo care sessions. Eight HRV features (5 in the time domain and 3 in the frequency domain) were used to visually and statistically compare the pre-kangaroo care and during-kangaroo care periods. Two of these features, capturing the percentage of heart rate decelerations and the extent of heart rate decelerations, were newly developed for preterm infants. A total of 191 kangaroo care sessions were investigated in 11 preterm infants. Despite clinically irrelevant changes in vital signs, 6 of the 8 HRV features (SD of normal-to-normal intervals, root mean square of the SD, percentage of consecutive normal-to-normal intervals that differ by >50 ms, SD of heart rate decelerations, high-frequency power, and low-frequency/high-frequency ratio) showed a visible and statistically significant difference (P heart rate decelerations. HRV-based features may be clinically useful for capturing the dynamic changes in autonomic regulation in response to kangaroo care and other changes in environment and state. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional Analyses of a Novel CITED2 Nonsynonymous Mutation in Chinese Tibetan Patients with Congenital Heart Disease.

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Liu, Shiming; Su, Zhaobing; Tan, Sainan; Ni, Bin; Pan, Hong; Liu, Beihong; Wang, Jing; Xiao, Jianmin; Chen, Qiuhong

2017-08-01

CITED2 gene is an important cardiac transcription factor that plays a fundamental role in the formation and development of embryonic cardiovascular. Previous studies have showed that knock-out of CITED2 in mice might result in various cardiac malformations. However, the mechanisms of CITED2 mutation on congenital heart disease (CHD) in Chinese Tibetan population are still poorly understood. In the present study, 187 unrelated Tibetan patients with CHD and 200 unrelated Tibetan healthy controls were screened for variants in the CITED2 gene; we subsequently identified one potential disease-causing mutation p.G143A in a 6-year-old girl with PDA and functional analyses of the mutation were carried out. Our study showed that the novel mutation of CITED2 significantly enhanced the expression activity of vascular endothelial growth factor (VEGF) under the role of co-receptor hypoxia inducible factor 1-aipha (HIF-1A), which is closely related with embryonic cardiac development. As a result, CITED2 gene mutation may play a significant role in the development of pediatric congenital heart disease.

Knock-in of large reporter genes in human cells via CRISPR/Cas9-induced homology-dependent and independent DNA repair.

Science.gov (United States)

He, Xiangjun; Tan, Chunlai; Wang, Feng; Wang, Yaofeng; Zhou, Rui; Cui, Dexuan; You, Wenxing; Zhao, Hui; Ren, Jianwei; Feng, Bo

2016-05-19

CRISPR/Cas9-induced site-specific DNA double-strand breaks (DSBs) can be repaired by homology-directed repair (HDR) or non-homologous end joining (NHEJ) pathways. Extensive efforts have been made to knock-in exogenous DNA to a selected genomic locus in human cells; which, however, has focused on HDR-based strategies and was proven inefficient. Here, we report that NHEJ pathway mediates efficient rejoining of genome and plasmids following CRISPR/Cas9-induced DNA DSBs, and promotes high-efficiency DNA integration in various human cell types. With this homology-independent knock-in strategy, integration of a 4.6 kb promoterless ires-eGFP fragment into the GAPDH locus yielded up to 20% GFP+ cells in somatic LO2 cells, and 1.70% GFP+ cells in human embryonic stem cells (ESCs). Quantitative comparison further demonstrated that the NHEJ-based knock-in is more efficient than HDR-mediated gene targeting in all human cell types examined. These data support that CRISPR/Cas9-induced NHEJ provides a valuable new path for efficient genome editing in human ESCs and somatic cells. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Aldosterone and aldosterone receptor antagonists in patients with chronic heart failure

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Nappi J

2011-06-01

Full Text Available Jean M Nappi, Adam SiegClinical Pharmacy and Outcome Sciences, South Carolina College of Pharmacy, Medical University of South Carolina Campus, Charleston, SC, USAAbstract: Aldosterone is a mineralocorticoid hormone synthesized by the adrenal glands that has several regulatory functions to help the body maintain normal volume status and electrolyte balance. Studies have shown significantly higher levels of aldosterone secretion in patients with congestive heart failure compared with normal patients. Elevated levels of aldosterone have been shown to elevate blood pressure, cause left ventricular hypertrophy, and promote cardiac fibrosis. An appreciation of the true role of aldosterone in patients with chronic heart failure did not become apparent until the publication of the Randomized Aldactone Evaluation Study. Until recently, the use of aldosterone receptor antagonists has been limited to patients with severe heart failure and patients with heart failure following myocardial infarction. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF study added additional evidence to support the expanded use of aldosterone receptor antagonists in heart failure patients. The results of the EMPHASIS-HF trial showed that patients with mild-to-moderate (New York Heart Association Class II heart failure had reductions in mortality and hospitalizations from the addition of eplerenone to optimal medical therapy. Evidence remains elusive about the exact mechanism by which aldosterone receptor antagonists improve heart failure morbidity and mortality. The benefits of aldosterone receptor antagonist use in heart failure must be weighed against the potential risk of complications, ie, hyperkalemia and, in the case of spironolactone, possible endocrine abnormalities, in particular gynecomastia. With appropriate monitoring, these risks can be minimized. We now have evidence that patients with mild-to-severe symptoms

A NEW METHOD FOR CHARACTERIZING THE KNOCK RESISTANCE OF LNG FUELS USED IN THE TRANSPORTATION MARKET

NARCIS (Netherlands)

Levinsky, Howard; Gersen, Sander; van Essen, Martijn; van Dijk, Gerco

2014-01-01

To ensure that the engines to be used in LNG-fueled vehicles are matched with the expected variations in fuel composition, the knock resistance of the fuel must be determined unambiguously. Rather than rely on empirical methods using gas mixtures and “standard” engines traditionally employed for

New Role for Interleukin-13 Receptor α1 in Myocardial Homeostasis and Heart Failure.

Science.gov (United States)

Amit, Uri; Kain, David; Wagner, Allon; Sahu, Avinash; Nevo-Caspi, Yael; Gonen, Nir; Molotski, Natali; Konfino, Tal; Landa, Natalie; Naftali-Shani, Nili; Blum, Galia; Merquiol, Emmanuelle; Karo-Atar, Danielle; Kanfi, Yariv; Paret, Gidi; Munitz, Ariel; Cohen, Haim Y; Ruppin, Eytan; Hannenhalli, Sridhar; Leor, Jonathan

2017-05-20

The immune system plays a pivotal role in myocardial homeostasis and response to injury. Interleukins-4 and -13 are anti-inflammatory type-2 cytokines, signaling via the common interleukin-13 receptor α1 chain and the type-2 interleukin-4 receptor. The role of interleukin-13 receptor α1 in the heart is unknown. We analyzed myocardial samples from human donors (n=136) and patients with end-stage heart failure (n=177). We found that the interleukin-13 receptor α1 is present in the myocardium and, together with the complementary type-2 interleukin-4 receptor chain Il4ra , is significantly downregulated in the hearts of patients with heart failure. Next, we showed that Il13ra1 -deficient mice develop severe myocardial dysfunction and dyssynchrony compared to wild-type mice (left ventricular ejection fraction 29.7±9.9 versus 45.0±8.0; P =0.004, left ventricular end-diastolic diameter 4.2±0.2 versus 3.92±0.3; P =0.03). A bioinformatic analysis of mouse hearts indicated that interleukin-13 receptor α1 regulates critical pathways in the heart other than the immune system, such as extracellular matrix (normalized enrichment score=1.90; false discovery rate q=0.005) and glucose metabolism (normalized enrichment score=-2.36; false discovery rate q=0). Deficiency of Il13ra1 was associated with reduced collagen deposition under normal and pressure-overload conditions. The results of our studies in humans and mice indicate, for the first time, a role of interleukin-13 receptor α1 in myocardial homeostasis and heart failure and suggests a new therapeutic target to treat heart disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Haemodynamic findings on cardiac CT in children with congenital heart disease

International Nuclear Information System (INIS)

Goo, Hyun Woo

2011-01-01

In patients with congenital heart disease, haemodynamic findings demonstrated on cardiac CT might provide useful hints for understanding the haemodynamics of cardiac defects. In contrast to morphological features depicted on cardiac CT, such haemodynamic findings on cardiac CT have not been comprehensively reviewed in patients with congenital heart disease. This article describes normal haemodynamic phenomena of cardiovascular structures and various abnormal haemodynamic findings with their mechanisms and clinical significance on cardiac CT in patients with congenital heart disease. (orig.)

Easi-CRISPR for creating knock-in and conditional knockout mouse models using long ssDNA donors.

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Miura, Hiromi; Quadros, Rolen M; Gurumurthy, Channabasavaiah B; Ohtsuka, Masato

2018-01-01

CRISPR/Cas9-based genome editing can easily generate knockout mouse models by disrupting the gene sequence, but its efficiency for creating models that require either insertion of exogenous DNA (knock-in) or replacement of genomic segments is very poor. The majority of mouse models used in research involve knock-in (reporters or recombinases) or gene replacement (e.g., conditional knockout alleles containing exons flanked by LoxP sites). A few methods for creating such models have been reported that use double-stranded DNA as donors, but their efficiency is typically 1-10% and therefore not suitable for routine use. We recently demonstrated that long single-stranded DNAs (ssDNAs) serve as very efficient donors, both for insertion and for gene replacement. We call this method efficient additions with ssDNA inserts-CRISPR (Easi-CRISPR) because it is a highly efficient technology (efficiency is typically 30-60% and reaches as high as 100% in some cases). The protocol takes ∼2 months to generate the founder mice.

Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH).

Science.gov (United States)

Dong, Bingzi; Endo, Itsuro; Ohnishi, Yukiyo; Kondo, Takeshi; Hasegawa, Tomoka; Amizuka, Norio; Kiyonari, Hiroshi; Shioi, Go; Abe, Masahiro; Fukumoto, Seiji; Matsumoto, Toshio

2015-11-01

Activating mutations of calcium-sensing receptor (CaSR) cause autosomal dominant hypocalcemia (ADH). ADH patients develop hypocalcemia, hyperphosphatemia, and hypercalciuria, similar to the clinical features of hypoparathyroidism. The current treatment of ADH is similar to the other forms of hypoparathyroidism, using active vitamin D3 or parathyroid hormone (PTH). However, these treatments aggravate hypercalciuria and renal calcification. Thus, new therapeutic strategies for ADH are needed. Calcilytics are allosteric antagonists of CaSR, and may be effective for the treatment of ADH caused by activating mutations of CaSR. In order to examine the effect of calcilytic JTT-305/MK-5442 on CaSR harboring activating mutations in the extracellular and transmembrane domains in vitro, we first transfected a mutated CaSR gene into HEK cells. JTT-305/MK-5442 suppressed the hypersensitivity to extracellular Ca(2+) of HEK cells transfected with the CaSR gene with activating mutations in the extracellular and transmembrane domains. We then selected two activating mutations locating in the extracellular (C129S) and transmembrane (A843E) domains, and generated two strains of CaSR knock-in mice to build an ADH mouse model. Both mutant mice mimicked almost all the clinical features of human ADH. JTT-305/MK-5442 treatment in vivo increased urinary cAMP excretion, improved serum and urinary calcium and phosphate levels by stimulating endogenous PTH secretion, and prevented renal calcification. In contrast, PTH(1-34) treatment normalized serum calcium and phosphate but could not reduce hypercalciuria or renal calcification. CaSR knock-in mice exhibited low bone turnover due to the deficiency of PTH, and JTT-305/MK-5442 as well as PTH(1-34) increased bone turnover and bone mineral density (BMD) in these mice. These results demonstrate that calcilytics can reverse almost all the phenotypes of ADH including hypercalciuria and renal calcification, and suggest that calcilytics can become a

Knock-Limited Performance of Triptane and 28-R Fuel Blends as Affected by Changes in Compression Ratio and in Engine Operating Variables

Science.gov (United States)

Brun, Rinaldo J.; Feder, Melvin S.; Fisher, William F.

1947-01-01

A knock-limited performance investigation was conducted on blends of triptane and 28-P fuel with a 12-cylinder, V-type, liquid-cooled aircraft engine of 1710-cubic-inch displacement at three compression ratios: 6.65, 7.93, and 9.68. At each compression ratio, the effect of changes in temperature of the inlet air to the auxiliary-stage supercharger and in fuel-air ratio were investigated at engine speeds of 2280 and. 3000 rpm. The results show that knock-limited engine performance, as improved by the use of triptane, allowed operation at both take-off and cruising power at a compression ratio of 9.68. At an inlet-air temperature of 60 deg F, an engine speed of 3000 rpm ; and a fuel-air ratio of 0,095 (approximately take-off conditions), a knock-limited engine output of 1500 brake horsepower was possible with 100-percent 28-R fuel at a compression ratio of 6.65; 20-percent triptane was required for the same power output at a compression ratio of 7.93, and 75 percent at a compression ratio of 9.68 allowed an output of 1480 brake horsepower. Knock-limited power output was more sensitive to changes in fuel-air ratio as the engine speed was increased from 2280 to 3000 rpm, as the compression ratio is raised from 6.65 to 9.68, or as the inlet-air temperature is raised from 0 deg to 120 deg F.

Generation of Pax6-IRES-EGFP knock-in mouse via the cloning-free CRISPR/Cas9 system to reliably visualize neurodevelopmental dynamics.

Science.gov (United States)

Inoue, Yukiko U; Morimoto, Yuki; Hoshino, Mikio; Inoue, Takayoshi

2018-07-01

Pax6 encodes a transcription factor that plays pivotal roles in eye development, early brain patterning, neocortical arealization, and so forth. Visualization of Pax6 expression dynamics in these events could offer numerous advantages to neurodevelopmental studies. While CRISPR/Cas9 system has dramatically accelerated one-step generation of knock-out mouse, establishment of gene-cassette knock-in mouse via zygote injection has been considered insufficient due to its low efficiency. Recently, an improved CRISPR/Cas9 system for effective gene-cassette knock-in has been reported, where the native form of guide RNAs (crRNA and tracrRNA) assembled with recombinant Cas9 protein are directly delivered into mouse fertilized eggs. Here we apply this strategy to insert IRES-EGFP-pA cassette into Pax6 locus and achieve efficient targeted insertions of the 1.8 kb reporter gene. In Pax6-IRES-EGFP mouse we have generated, EGFP-positive cells reside in the eyes and cerebellum as endogenous Pax6 expressing cells at postnatal day 2. At the early embryonic stages when the embryos are transparent, EGFP-positive regions can be easily identified without PCR-based genotyping, precisely recapitulating the endogenous Pax6 expression patterns. Remarkably, at E12.5, the graded expression patterns of Pax6 in the developing neocortex now become recognizable in our knock-in mice, serving a sufficiently sensitive and useful tool to precisely visualize neurodevelopmental processes. Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

When the heart kills the liver: acute liver failure in congestive heart failure

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Saner FH

2009-12-01

Full Text Available Abstract Congestive heart failure as a cause of acute liver failure is rarely documented with only a few cases. Although the pathophysiology is poorly understood, there is rising evidence, that low cardiac output with consecutive reduction in hepatic blood flow is a main causing factor, rather than hypotension. In the setting of acute liver failure due to congestive heart failure, clinical signs of the latter can be absent, which requires an appropriate diagnostic approach. As a reference center for acute liver failure and liver transplantation we recorded from May 2003 to December 2007 202 admissions with the primary diagnoses acute liver failure. 13/202 was due to congestive heart failure, which was associated with a mortality rate of 54%. Leading cause of death was the underlying heart failure. Asparagine transaminase (AST, bilirubin, and international normalized ratio (INR did not differ significantly in surviving and deceased patients at admission. Despite both groups had signs of cardiogenic shock, the cardiac index (CI was significantly higher in the survival group on admission as compared with non-survivors (2.1 L/min/m2 vs. 1.6 L/min/m2, p = 0.04. Central venous - and pulmonary wedge pressure did not differ significantly. Remarkable improvement of liver function was recorded in the group, who recovered from cardiogenic shock. In conclusion, patients with acute liver failure require an appropriate diagnostic approach. Congestive heart failure should always be considered as a possible cause of acute liver failure.

Vascular and parenchymal amyloid pathology in an Alzheimer disease knock-in mouse model: interplay with cerebral blood flow.

Science.gov (United States)

Li, Hongmei; Guo, Qinxi; Inoue, Taeko; Polito, Vinicia A; Tabuchi, Katsuhiko; Hammer, Robert E; Pautler, Robia G; Taffet, George E; Zheng, Hui

2014-08-09

Accumulation and deposition of β-amyloid peptides (Aβ) in the brain is a central event in the pathogenesis of Alzheimer's disease (AD). Besides the parenchymal pathology, Aβ is known to undergo active transport across the blood-brain barrier and cerebral amyloid angiopathy (CAA) is a prominent feature in the majority of AD. Although impaired cerebral blood flow (CBF) has been implicated in faulty Aβ transport and clearance, and cerebral hypoperfusion can exist in the pre-clinical phase of Alzheimer's disease (AD), it is still unclear whether it is one of the causal factors for AD pathogenesis, or an early consequence of a multi-factor condition that would lead to AD at late stage. To study the potential interaction between faulty CBF and amyloid accumulation in clinical-relevant situation, we generated a new amyloid precursor protein (APP) knock-in allele that expresses humanized Aβ and a Dutch mutation in addition to Swedish/London mutations and compared this line with an equivalent knock-in line but in the absence of the Dutch mutation, both crossed onto the PS1M146V knock-in background. Introduction of the Dutch mutation results in robust CAA and parenchymal Aβ pathology, age-dependent reduction of spatial learning and memory deficits, and CBF reduction as detected by fMRI. Direct manipulation of CBF by transverse aortic constriction surgery on the left common carotid artery caused differential changes in CBF in the anterior and middle region of the cortex, where it is reduced on the left side and increased on the right side. However these perturbations in CBF resulted in the same effect: both significantly exacerbate CAA and amyloid pathology. Our study reveals a direct and positive link between vascular and parenchymal Aβ; both can be modulated by CBF. The new APP knock-in mouse model recapitulates many symptoms of AD including progressive vascular and parenchymal Aβ pathology and behavioral deficits in the absence of APP overexpression.

Vertebral scale system to measure canine heart size in radiographs

International Nuclear Information System (INIS)

Buchanan, J.W.; Bucheler, J.

1995-01-01

A method for measuring canine heart size in radiographs was developed on the basis that there is a good correlation between heart size and body length regardless of the conformation of the thorax. The lengths of the long and short axes of the heart of 100 clinically normal dogs were determined with calipers, and the dimensions were scaled against the length of vertebrae dorsal to the heart beginning with T4. The sum of the long and short axes of the heart expressed as vertebral heart size was 9.7 +/- 0.5 vertebrae. The differences between dogs with a wide or deep thorax, males and females, and right or left lateral recumbency were not significant. The caudal vena cava was 0.75 vertebrae +/- 0.13 in comparison to the length of the vertebra over the tracheal bifurcation

Pyrophosphate heart scintigram in children with progressive muscular dystrophy

Energy Technology Data Exchange (ETDEWEB)

Duska, F; Nesvadba, Z; Zdansky, P; Novak, J; Kubicek, J; Kafka, P; Vizda, J; Mazurova, Y

1984-08-01

A pyrophosphate heart scintigram was obtained in 16 boys with progressive muscular dystrophy Duchenne. All of them showed pathological ECG findings and high plasma levels of CK, AST, ALT and LD. In 4 patients the scintigram was distinctly positive and in further 3 it reached borderline values. The remaining 9 boys had normal scintigraphic findings. Those with a positive heart scintigram had very high plasma levels of the enzymes under study which was suggestive of current progression of the disease. There was, however, no relation between heart scintigraphy and the affliction of the skeletal muscles expressed by means of an index.

Verification of rubidium-82 for heart studies

International Nuclear Information System (INIS)

Budinger, T.F.; Yano, Y.; Twitchell, J.A.; Brennan, K.M.

1985-01-01

Whereas 82 Rb has been shown to reflect heart blood-flow under normal circumstances and has the great benefit of being available from a noncyclotron source, there remains a question with regard to the physiology of rubidium transport into the heart muscle. The fraction of the amount of the rubidium tracer that goes into the heart varies with flow, and, unfortunately, the amount that accumulates in the muscle will not therefore be proportional to flow. Over the past three years, the authors have re-evaluated this question and determined that the uptake of rubidium in the myocardium follows a simple model of conservation of mass wherein the amount that is present is equal to the product of flow times extraction

Radiocardiographic determination of the stroke volume and of the heart minute volume in athletes

Energy Technology Data Exchange (ETDEWEB)

Sattler, R; Stoll, W [Friedrich-Schiller-Universitaet, Jena (German Democratic Republic). Radiologische Klinik

1981-11-01

Radiocardiography, a novel radioisotope method for the problemless determination of many cardiodynamic parameters which can be applied also at given physical exercise is presented. On the basis of stroke volume and heart minute volume values from 35 athletes practising different sports and of a comparison with normal values reported in the literature, differences in the cardiac adaptation and the function of athletic hearts and so-called normal hearts are pointed out. The stroke volume of endurance-trained athletes exceeds that of untrained individuals by 30-40 ml. Under exercise the increase of the stroke volume is considerably greater in endurance athletes than in individuals practising other sports or in untrained subjects. At rest the values of the heart minute volume are almost the same in athletes and untrained individuals. Under exercise the heart minute volume of endurance athletes (40 l/min) is nearly twice that of untrained individuals (volume reserve of the athlete).

Radiocardiographic determination of the stroke volume and of the heart minute volume in athletes

International Nuclear Information System (INIS)

Sattler, R.; Stoll, W.

1981-01-01

Radiocardiography, a novel radioisotope method for the problemless determination of many cardiodynamic parameters which can be applied also at given physical exercise is presented. On the basis of stroke volume and heart minute volume values from 35 athletes practising different sports and of a comparison with normal values reported in the literature, differences in the cardiac adaptation and the function of athletic hearts and so-called normal hearts are pointed out. The stroke volume of endurance-trained athetes exceed that of untrained individuals by 30-40 ml. Under exercise the increase of the stroke volume is considerably greater in endurance athletes than in individuals practising other sports or in untrained subjects. At rest the values of the heart minute volume are almost the same in athletes and untrained individuals. Under exercise the heart minute volume of endurance athletes (40 l/min) is nearly twice that of untrained individuals (volume reserve of the athlete). (author)

A new approach for low-cost noninvasive detection of asymptomatic heart disease at rest.

Science.gov (United States)

DeMarzo, Arthur P; Calvin, James E

2007-01-01

It would be useful to have an inexpensive, noninvasive point-of-care test for early detection of asymptomatic heart disease. This study used impedance cardiography (ICG) in a new way to assess heart function that did not use stroke volume or cardiac output. There is a model of the ICG dZ/dt waveform that may be used as a template to represent normal heart function. The hypothesis was that a dZ/dt waveform which deviates from that template should indicate heart dysfunction and therefore heart disease. The objective was to assess the accuracy of this new ICG approach, using echocardiography as the standard. Thirty-four outpatients undergoing echocardiographic testing were tested by ICG while sitting upright and supine. All patients had no symptoms or history of a structural or functional heart disorder. Echocardiographic testing showed 17 patients with abnormalities and 17 as normal. ICG testing yielded 16 true positives for heart dysfunction with 1 false negative (sensitivity = 94%) and 17 true negatives with no false positives (specificity = 100%). Considering that the cost, technical skill, and time required for this ICG test are comparable to those of an electrocardiograph, this new approach has potential as a point-of-care screening test for asymptomatic heart disease.

Peripartum haemodynamic status of bitches with normal birth or dystocia.

Science.gov (United States)

Lúcio, C F; Silva, L C G; Rodrigues, J A; Veiga, G A L; Vannucchi, C I

2009-07-01

There has been limited investigation of parturition in the bitch and there is little information published on clinical and obstetrical examination other than opinion and anecdote. While there are substantial data on haemodynamic and vascular changes during normal parturition in humans, little is known about the physiological events in the dog. This study was aimed at maternal haemodynamic changes occurring during normal parturition and to investigate how these were modified in bitches with dystocia (DYST) treated either medically or via assisted delivery and caesarean operation. Three groups of 10 bitches were investigated; those with normal parturition, those with DYST corrected by manipulative assistance or caesarean operation and those with uterine inertia treated by oxytocin administration. Heart rate, systolic and diastolic blood pressure, electrocardiogram and blood glucose concentration were measured pre-partum, intra-partum, immediately after parturition and 1 h later. Heart rate was high at all times throughout the study and the majority of bitches had normal sinus rhythm. Blood pressure was generally within the normal range, and although systolic and diastolic blood pressure was highest during the intra-partum period and sometimes during the immediate post-partum period, there were no significant differences between groups. All bitches had blood glucose concentrations within the normal range throughout the study although pre-partum concentrations were statistically lower than many of the other time periods. The study provides useful physiological data that will facilitate monitoring and clinical management of bitches throughout normal parturition and DYST.

HEART ABNORMALITY CLASSIFICATIONS USING FOURIER TRANSFORMS METHOD AND NEURAL NETWORKS

Directory of Open Access Journals (Sweden)

Endah Purwanti

2014-05-01

Full Text Available Health problems with cardiovascular system disorder are still ranked high globally. One way to detect abnormalities in the cardiovascular system especially in the heart is through the electrocardiogram (ECG reading. However, reading ECG recording needs experience and expertise, software-based neural networks has designed to help identify any abnormalities ofthe heart through electrocardiogram digital image. This image is processed using image processing methods to obtain ordinate chart which representing the heart’s electrical potential. Feature extraction using Fourier transforms which are divided into several numbers of coefficients. As the software input, Fourier transforms coefficient have been normalized. Output of this software is divided into three classes, namely heart with atrial fibrillation, coronary heart disease and normal. Maximum accuracy rate ofthis software is 95.45%, with the distribution of the Fourier transform coefficients 1/8 and number of nodes 5, while minimum accuracy rate of this software at least 68.18% by distribution of the Fourier transform coefficients 1/32 and the number of nodes 32. Overall result accuracy rate of this software has an average of86.05% and standard deviation of7.82.

Rac1-PAK2 pathway is essential for zebrafish heart regeneration

Energy Technology Data Exchange (ETDEWEB)

Peng, Xiangwen [State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai 201203 (China); He, Quanze [Center for Reproduction and Genetics, Suzhou Municipal Hospital, Jiangsu 215002 (China); Li, Guobao; Ma, Jinmin [State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai 201203 (China); Zhong, Tao P., E-mail: taozhongfudan@yahoo.com [State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai 201203 (China); Department of Medicine, Vanderbilt University School of Medicine, TN 37232 (United States)

2016-04-15

P-21 activated kinases, or PAKs, are serine–threonine kinases that play important roles in diverse heart functions include heart development, cardiovascular development and function in a range of models; however, the mechanisms by which PAKs mediate heart regeneration are unknown. Here, we demonstrate that PAK2 and PAK4 expression is induced in cardiomyocytes and vessels, respectively, following zebrafish heart injury. Inhibition of PAK2 and PAK4 using a specific small molecule inhibitor impedes cardiomyocyte proliferation/dedifferentiation and cardiovascular regeneration, respectively. Cdc42 is specifically expressed in the ventricle and may function upstream of PAK2 but not PAK4 under normal conditions and that cardiomyocyte proliferentation during heart regeneration relies on Rac1-mediated activation of Pak2. Our results indicate that PAKs play a key role in heart regeneration.

Rac1-PAK2 pathway is essential for zebrafish heart regeneration

International Nuclear Information System (INIS)

Peng, Xiangwen; He, Quanze; Li, Guobao; Ma, Jinmin; Zhong, Tao P.

2016-01-01

P-21 activated kinases, or PAKs, are serine–threonine kinases that play important roles in diverse heart functions include heart development, cardiovascular development and function in a range of models; however, the mechanisms by which PAKs mediate heart regeneration are unknown. Here, we demonstrate that PAK2 and PAK4 expression is induced in cardiomyocytes and vessels, respectively, following zebrafish heart injury. Inhibition of PAK2 and PAK4 using a specific small molecule inhibitor impedes cardiomyocyte proliferation/dedifferentiation and cardiovascular regeneration, respectively. Cdc42 is specifically expressed in the ventricle and may function upstream of PAK2 but not PAK4 under normal conditions and that cardiomyocyte proliferentation during heart regeneration relies on Rac1-mediated activation of Pak2. Our results indicate that PAKs play a key role in heart regeneration.

[Improvement in functional capacity after levothyroxine treatment in patients with chronic heart failure and subclinical hypothyroidism].

Science.gov (United States)

Curotto Grasiosi, Jorge; Peressotti, Bruno; Machado, Rogelio A; Filipini, Eduardo C; Angel, Adriana; Delgado, Jorge; Cortez Quiroga, Gustavo A; Rus Mansilla, Carmen; Martínez Quesada, María del Mar; Degregorio, Alejandro; Cordero, Diego J; Dak, Marcelo; Izurieta, Carlos; Esper, Ricardo J

2013-10-01

To assess whether levothyroxine treatment improves functional capacity in patients with chronic heart failure (New York Heart Association class i-iii) and subclinical hypothyroidism. One hundred and sixty-three outpatients with stable chronic heart failure followed up for at least 6 months were enrolled. A physical examination was performed, and laboratory tests including thyroid hormone levels, Doppler echocardiogram, radionuclide ventriculography, and Holter monitoring were requested. Functional capacity was assessed by of the 6-min walk test. Patients with subclinical hypothyroidism were detected and, after undergoing the s6-min walk test, were given replacement therapy. When they reached normal thyrotropin (TSH) levels, the 6-min walk test was performed again. The distance walked in both tests was recorded, and the difference in meters covered by each patient was analyzed. Prevalence of subclinical hypothyroidism in patients with heart failure was 13%. These patients walked 292±63m while they were hypothyroid and 350±76m when TSH levels returned to normal, a difference of 58±11m (P<.011). Patients with normal baseline TSH levels showed no significant difference between the 2 6-min walk tests. Patients with chronic heart failure and subclinical hypothyroidism significantly improved their physical performance when normal TSH levels were reached. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Numerical Investigation of Injection Timing Influence on Fuel Slip and Influence of Compression Ratio on Knock Occurrence in Conventional Dual Fuel Engine

Directory of Open Access Journals (Sweden)

Mario Sremec

2017-12-01

Full Text Available Compressed natural gas can be used in diesel engine with great benefits, but because of its low reactivity it is usually used in a so called dual fuel combustion process. Optimal parameters for dual fuel engines are not yet investigated thoroughly which is the motivation for this work. In this work, a numerical study performed in a cycle simulation tool (AVL Boost v2013 on the influence of different injection timings on fuel slip into exhaust and influence of compression ratio on knock phenomena in port injected dual fuel engine was conducted. The introduction of natural gas into the intake port of a diesel engine usually results in some fuel slipping into the exhaust port due to valve overlap. By analysing the simulation results, the injection strategy that significantly decreases the natural gas slip is defined. The knock occurrence study showed that the highest allowed compression ratio that will result in knock free operation of the presented engine is 18 for ambient intake condition, while for charged intake conditions the compression ratio should be lowered to 16.

Total excitation of the isolated human heart

NARCIS (Netherlands)

Durrer, D.; Dam, R.Th. van; Freud, G.E.; Janse, M.J.; Meijler, F.L.; Arzbaecher, R.C.

To obtain information conceming the time course and instantaneous distribution of the excitatory process of the normal human healt, studies were made on isolated human hearts from seven individuals who died from various cerebral conditions, but who had no history of cardiac disease. Measurements

Dysfunction of an On-X Heart Valve by Pannus.

Science.gov (United States)

Abad, Cipriano; Urso, Stefano; Gomez, Elsa; De la Vega, Maria

2016-09-01

A 68-year-old woman with a history of previous double-valve replacement with On-X mechanical heart valves presented with clinical, echocardiographic and cardiac catheterization signs of obstruction of the On-X tricuspid heart valve prosthesis. The patient was successfully reoperated, but at surgery the valve was seen to be invaded by an abnormal overgrowth of pannus that blocked one of the leaflets. A small amount of non-obstructive fresh thrombus was also observed. The valve was successfully replaced with a biological heart valve prosthesis. The patient was discharged home, and is doing well four months after the operation, when echocardiography demonstrated normal function in the tricuspid valve. The present case represents the first ever report of pannus formation and subsequent dysfunction in an On-X heart valve, and also the first case of tricuspid valve malfunction and obstruction using this type of heart valve substitute.

Sqstm1 knock-down causes a locomotor phenotype ameliorated by rapamycin in a zebrafish model of ALS/FTLD.

Science.gov (United States)

Lattante, Serena; de Calbiac, Hortense; Le Ber, Isabelle; Brice, Alexis; Ciura, Sorana; Kabashi, Edor

2015-03-15

Mutations in SQSTM1, encoding for the protein SQSTM1/p62, have been recently reported in 1-3.5% of patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration (ALS/FTLD). Inclusions positive for SQSTM1/p62 have been detected in patients with neurodegenerative disorders, including ALS/FTLD. In order to investigate the pathogenic mechanisms induced by SQSTM1 mutations in ALS/FTLD, we developed a zebrafish model. Knock-down of the sqstm1 zebrafish ortholog, as well as impairment of its splicing, led to a specific phenotype, consisting of behavioral and axonal anomalies. Here, we report swimming deficits associated with shorter motor neuronal axons that could be rescued by the overexpression of wild-type human SQSTM1. Interestingly, no rescue of the loss-of-function phenotype was observed when overexpressing human SQSTM1 constructs carrying ALS/FTLD-related mutations. Consistent with its role in autophagy regulation, we found increased mTOR levels upon knock-down of sqstm1. Furthermore, treatment of zebrafish embryos with rapamycin, a known inhibitor of the mTOR pathway, yielded an amelioration of the locomotor phenotype in the sqstm1 knock-down model. Our results suggest that loss-of-function of SQSTM1 causes phenotypic features characterized by locomotor deficits and motor neuron axonal defects that are associated with a misregulation of autophagic processes. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of atrioventricular conduction on heart rate variability

KAUST Repository

Ahmad, Talha Jamal; Ali, Hussnain; Majeed, S. M Imran; Khan, Shoab A.

2011-01-01

This paper discusses the effect of atrioventricular conduction time (AVCT) on the short-term Heart Rate Variability (HRV) by computing HRV parameters using intervals between the onsets of successive P waves (PP time series) for three groups: normal

In situ Raman study of redox state changes of mitochondrial cytochromes in a perfused rat heart

DEFF Research Database (Denmark)

Brazhe, Nadezda; Treiman, Marek; Faricelli, Barbara

2013-01-01

We developed a Raman spectroscopy-based approach for simultaneous study of redox changes in c-and b-type cytochromes and for a semiquantitative estimation of the amount of oxygenated myoglobin in a perfused rat heart. Excitation at 532 nm was used to obtain Raman scattering of the myocardial...... surface of the isolated heart at normal and hypoxic conditions. Raman spectra of the heart under normal pO2 demonstrate unique peaks attributable to reduced c-and b-type cytochromes and oxymyoglobin (oMb). The cytochrome peaks decreased in intensity upon FCCP treatment, as predicted from uncoupling...

Erythroblast differentiation at spleen in Q137E mutant ribosomal protein S19 gene knock-in C57BL/6J mice.

Science.gov (United States)

Yamanegi, Koji; Yamada, Naoko; Nakasho, Keiji; Nishiura, Hiroshi

2018-01-01

We recently found that erythroblast-like cells derived from human leukaemia K562 cells express C5a receptor (C5aR) and produce its antagonistic and agonistic ligand ribosomal protein S19 (RP S19) polymer, which is cross-linked between K122 and Q137 by tissue transglutaminases. RP S19 polymer binds to the reciprocal C5aRs on erythroblast-like cells and macrophage-like cells derived from human monocytic THP-1 cells and promotes differentiation into reticulocyte-like cells through enucleation in vitro. To examine the roles of RP S19 polymer in mouse erythropoiesis, we prepared Q137E mutant RP S19 gene knock-in C57BL/6J mice. In contrast to wild-type mice, erythroblast numbers at the preliminary stage (CD71 high /TER119 low ) in spleen based on transferrin receptor (CD71) and glycophorin A (TER119) values and erythrocyte numbers in orbital artery bloods were not largely changed in knock-in mice. Conversely, erythroblast numbers at the early stage (CD71 high /TER119 high ) were significantly decreased in spleen by knock-in mice. The reduction of early erythroblast numbers in spleen was enhanced by the phenylhydrazine-induced pernicious anemia model knock-in mice and was rescued by a functional analogue of RP S19 dimer S-tagged C5a/RP S19. These data indicated that RP S19 polymer plays the roles in the early erythroblast differentiation of C57BL/6J mouse spleen. Copyright © 2017 Elsevier GmbH. All rights reserved.

Neurofascin Knock Down in the Basolateral Amygdala Mediates Resilience of Memory and Plasticity in the Dorsal Dentate Gyrus Under Stress.

Science.gov (United States)

Saha, Rinki; Kriebel, Martin; Volkmer, Hansjürgen; Richter-Levin, Gal; Albrecht, Anne

2018-02-05

Activation of the amygdala is one of the hallmarks of acute stress reactions and a central element of the negative impact of stress on hippocampus-dependent memory and cognition. Stress-induced psychopathologies, such as posttraumatic stress disorder, exhibit a sustained hyperactivity of the amygdala, triggered at least in part by deficits in GABAergic inhibition that lead to shifts in amygdalo-hippocampal interaction. Here, we have utilized lentiviral knock down of neurofascin to reduce GABAergic inhibition specifically at the axon initial segment (AIS) of principal neurons within the basolateral amygdala (BLA) of rats. Metaplastic effects of such a BLA modulation on hippocampal synaptic function were assessed using BLA priming prior to the induction of long-term potentiation (LTP) on dentate gyrus synapses in anesthetized rats in vivo. The knock down of neurofascin in the BLA prevented a priming-induced impairment on LTP maintenance in the dentate gyrus. At the behavioral level, a similar effect was observable, with neurofascin knock down preventing the detrimental impact of acute traumatic stress on hippocampus-dependent spatial memory retrieval in a water maze task. These findings suggest that reducing GABAergic inhibition specifically at the AIS synapses of the BLA alters amygdalo-hippocampal interactions such that it attenuates the adverse impact of acute stress exposure on cognition-related hippocampal functions.

Towards mastering CRISPR-induced gene knock-in in plants: Survey of key features and focus on the model Physcomitrella patens.

Science.gov (United States)

Collonnier, Cécile; Guyon-Debast, Anouchka; Maclot, François; Mara, Kostlend; Charlot, Florence; Nogué, Fabien

2017-05-15

Beyond its predominant role in human and animal therapy, the CRISPR-Cas9 system has also become an essential tool for plant research and plant breeding. Agronomic applications rely on the mastery of gene inactivation and gene modification. However, if the knock-out of genes by non-homologous end-joining (NHEJ)-mediated repair of the targeted double-strand breaks (DSBs) induced by the CRISPR-Cas9 system is rather well mastered, the knock-in of genes by homology-driven repair or end-joining remains difficult to perform efficiently in higher plants. In this review, we describe the different approaches that can be tested to improve the efficiency of CRISPR-induced gene modification in plants, which include the use of optimal transformation and regeneration protocols, the design of appropriate guide RNAs and donor templates and the choice of nucleases and means of delivery. We also present what can be done to orient DNA repair pathways in the target cells, and we show how the moss Physcomitrella patens can be used as a model plant to better understand what DNA repair mechanisms are involved, and how this knowledge could eventually be used to define more performant strategies of CRISPR-induced gene knock-in. Copyright © 2017 Elsevier Inc. All rights reserved.

Knock-in strategy at 3'-end of Crx gene by CRISPR/Cas9 system shows the gene expression profiles during human photoreceptor differentiation.

Science.gov (United States)

Homma, Kohei; Usui, Sumiko; Kaneda, Makoto

2017-03-01

Fluorescent reporter gene knock-in induced pluripotent stem cell (iPSC) lines have been used to evaluate the efficiency of differentiation into specific cell lineages. Here, we report a knock-in strategy for the generation of human iPSC reporter lines in which a 2A peptide sequence and a red fluorescent protein (E2-Crimson) gene were inserted at the termination codon of the cone-rod homeobox (Crx) gene, a photoreceptor-specific transcriptional factor gene. The knock-in iPSC lines were differentiated into fluorescence-expressing cells in 3D retinal differentiation culture, and the fluorescent cells also expressed Crx specifically in the nucleus. We found that the fluorescence intensity was positively correlated with the expression levels of Crx mRNA and that fluorescent cells expressed rod photoreceptor-specific genes in the later stage of differentiation. Finally, we treated the fluorescent cells with DAPT, a Notch inhibitor, and found that DAPT-enhanced retinal differentiation was associated with up-regulation of Crx, Otx2 and NeuroD1, and down-regulation of Hes5 and Ngn2. These suggest that this knock-in strategy at the 3'-end of the target gene, combined with the 2A peptide linked to fluorescent proteins, offers a useful tool for labeling specific cell lineages or monitoring expression of any marker genes without affecting the function of the target gene. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Can complexity decrease in congestive heart failure?

Science.gov (United States)

Mukherjee, Sayan; Palit, Sanjay Kumar; Banerjee, Santo; Ariffin, M. R. K.; Rondoni, Lamberto; Bhattacharya, D. K.

2015-12-01

The complexity of a signal can be measured by the Recurrence period density entropy (RPDE) from the reconstructed phase space. We have chosen a window based RPDE method for the classification of signals, as RPDE is an average entropic measure of the whole phase space. We have observed the changes in the complexity in cardiac signals of normal healthy person (NHP) and congestive heart failure patients (CHFP). The results show that the cardiac dynamics of a healthy subject is more complex and random compare to the same for a heart failure patient, whose dynamics is more deterministic. We have constructed a general threshold to distinguish the border line between a healthy and a congestive heart failure dynamics. The results may be useful for wide range for physiological and biomedical analysis.

Ratio of organs to blood of mercury during its uptake by normal and acatalasemic mice

International Nuclear Information System (INIS)

Ogata, M.; Aikoh, H.

1987-01-01

The brain/blood, liver/blood, and heart/blood ratios of acatalasemic mice after intraperitoneal injection of labelled metallic mercury or after exposure to labelled metallic mercury vapor were significantly higher than those of normal mice. These ratios of normal or acatalasemic mice after injection with metallic mercury or exposure to metallic mercury vapor were significantly higher than those of normal and acatalasemic mice injected with mercuric ion. The amount of metallic mercury exhaled from acatalasemic mice injected with metallic mercury was greater than that from normal mice, indicating that the level of metallic mercury in blood of the former was higher than that of the latter. Actually, metallic mercury in the blood of acatalasemic mice injected with metallic mercury is higher than that in the blood of normal mice, suggesting that metallic mercury is easily transferred from blood to brain, liver, kidney, and heart

Valvular Heart Disease in Heart Failure

Directory of Open Access Journals (Sweden)

Giuseppe MC Rosano

2017-01-01

Full Text Available Structural valvular heart disease may be the cause of heart failure or may worsen the clinical status of patients with heart failure. Heart failure may also develop in patients treated with valve surgery. Patients with heart failure with valvular heart disease are at increased risk of events including sudden cardiac death. Before considering intervention (surgical or percutaneous all patients should receive appropriate medical and device therapy taking into account that vasodilators must be used with caution in patients with severe aortic stenosis. Numerous percutaneous and/or hybrid procedures have been introduced in the past few years and they are changing the management of valvular heart disease. In patients with heart failure and valvular heart disease, either primary or functional, the whole process of decision-making should be staged through a comprehensive evaluation of the risk– benefit ratio of different treatment strategies and should be made by a multidisciplinary ‘heart team’ with a particular expertise in valvular heart disease. The heart team should include heart failure cardiologists, cardiac surgeons/structural valve interventionists, imaging specialists, anaesthetists, geriatricians and intensive care specialists. This article will review recent developments and distill practical guidance in the management of this important heart failure co-morbidity.

[BLG gene knockout and hLF gene knock-in at BLG locus in goat by TALENs].

Science.gov (United States)

Song, Shaozheng; Zhu, Mengmin; Yuan, Yuguo; Rong, Yao; Xu, Sheng; Chen, Si; Mei, Junyan; Cheng, Yong

2016-03-01

To knock out β-lactoglobulin (BLG) gene and insert human lactoferrin (hLF) coding sequence at BLG locus of goat, the transcription activator-like effector nucleases (TALEN) mediated recombination was used to edit the BLG gene of goat fetal fibroblast, then as donor cells for somatic cell nuclear transfer. We designed a pair of specific plasmid TALEN-3-L/R for goat BLG exon III recognition sites, and BLC14-TK vector containing a negative selection gene HSV-TK, was used for the knock in of hLF gene. TALENs plasmids were transfected into the goat fetal fibroblast cells, and the cells were screened three days by 2 μg/mL puromycin. DNA cleavage activities of cells were verified by PCR amplification and DNA production sequencing. Then, targeting vector BLC14-TK and plasmids TALEN-3-L/R were co-transfected into goat fetal fibroblasts, both 700 μg/mL G418 and 2 μg/mL GCV were simultaneously used to screen G418-resistant cells. Detections of integration and recombination were implemented to obtain cells with hLF gene site-specific integration. We chose targeting cells as donor cells for somatic cell nuclear transfer. The mutagenicity of TALEN-3-L/R was between 25% and 30%. A total of 335 reconstructed embryos with 6 BLG-/hLF+ targeting cell lines were transferred into 16 recipient goats. There were 9 pregnancies confirmed by ultrasound on day 30 to 35 (pregnancy rate of 39.1%), and one of 50-day-old fetus with BLG-/hLF+ was achieved. These results provide the basis for hLF gene knock-in at BLG locus of goat and cultivating transgenic goat of low allergens and rich hLF in the milk.

The pyrophosphate heart scintigram in children with progressive muscular dystrophy

International Nuclear Information System (INIS)

Duska, F.; Nesvadba, Z.; Zdansky, P.; Novak, J.; Kubicek, J.; Kafka, P.; Vizda, J.; Mazurova, Y.; Karlova Univ., Hradec Kralove; Karlova Univ., Hradec Kralove

1984-01-01

A pyrophosphate heart scintigram was obtained in 16 boys with progressive muscular dystrophy Duchenne. All of them showed pathological ECG findings and high plasma levels of CK, AST, ALT and LD. In 4 patients the scintigram was distinctly positive and in further 3 it reached borderline values. The remaining 9 boys had normal scintigraphic findings. Those with a positive heart scintigram had very high plasma levels of the enzymes under study which was suggestive of current progression of the disease. There was, however, no relation between heart scintigraphy and the affliction of the skeletal muscles expressed by means of an index. (orig.) [de

Lung and Heart Sounds Analysis: State-of-the-Art and Future Trends.

Science.gov (United States)

Padilla-Ortiz, Ana L; Ibarra, David

2018-01-01

Lung sounds, which include all sounds that are produced during the mechanism of respiration, may be classified into normal breath sounds and adventitious sounds. Normal breath sounds occur when no respiratory problems exist, whereas adventitious lung sounds (wheeze, rhonchi, crackle, etc.) are usually associated with certain pulmonary pathologies. Heart and lung sounds that are heard using a stethoscope are the result of mechanical interactions that indicate operation of cardiac and respiratory systems, respectively. In this article, we review the research conducted during the last six years on lung and heart sounds, instrumentation and data sources (sensors and databases), technological advances, and perspectives in processing and data analysis. Our review suggests that chronic obstructive pulmonary disease (COPD) and asthma are the most common respiratory diseases reported on in the literature; related diseases that are less analyzed include chronic bronchitis, idiopathic pulmonary fibrosis, congestive heart failure, and parenchymal pathology. Some new findings regarding the methodologies associated with advances in the electronic stethoscope have been presented for the auscultatory heart sound signaling process, including analysis and clarification of resulting sounds to create a diagnosis based on a quantifiable medical assessment. The availability of automatic interpretation of high precision of heart and lung sounds opens interesting possibilities for cardiovascular diagnosis as well as potential for intelligent diagnosis of heart and lung diseases.

An analysis of heart rhythm dynamics using a three-coupled oscillator model

International Nuclear Information System (INIS)

Gois, Sandra R.F.S.M.; Savi, Marcelo A.

2009-01-01

Rhythmic phenomena represent one of the most striking manifestations of the dynamic behavior in biological systems. Understanding the mechanisms responsible for biological rhythms is crucial for the comprehension of the dynamics of life. Natural rhythms could be either regular or irregular over time and space. Each kind of dynamical behavior may be related to both normal and pathological physiological functioning. The cardiac conducting system can be treated as a network of self-excitatory elements and, since these elements exhibit oscillatory behavior, they can be modeled as nonlinear oscillators. This paper proposes a mathematical model to describe heart rhythms considering three modified Van der Pol oscillators connected with time delay couplings. Therefore, the heart dynamics is represented by a system of differential difference equations. Numerical simulations are carried out presenting qualitative agreement with the general heart rhythm behavior. Normal and pathological rhythms represented by the ECG signals are reproduced. Pathological rhythms are generated by either the coupling alterations that represents communications aspects in the heart electric system or forcing excitation representing external pacemaker excitation.

Study of trace element metabolism in normal and cancerous mice using multitracer technique

International Nuclear Information System (INIS)

Wang Xiao; Kong Fuquan; Zhao Kui; Zhang Xiang; Qin Zhi

2008-01-01

A radioactive multitracer solution of the 24 elements, e.g. Be, Na, K, Rb, Mg, Ca, Sr, Ga, As, Sc, V, Cr, Mn, Co, Fe, Zn, Y, Zr, Mo, Nb, To, Ru, Ag and In, was obtained from the nuclear reaction of 25 MeV/u 40 Ar + Se with a series of chemical process. The multitracer solution was orally administered to normal and muscular turnout-bearing mice of male Balb/c mice. Urine and faeces samples of mice were collected. The two group mice were saerificed after 96 h. The uptake of 17 elements, Na, Rb, Ga, As, Sc, V, Cr, Mn, Co, Fe, Zn, Y, Zr, Tc, Ru, Ag and In, were simultaneously detected in normal mice while 15 elements, Na, Rb, Ga, Sc, V, Cr, Mn, Co, Fe, Y, Zr, Tc, Ru, Ag and In, were simultaneously detected in tumour-bearing mice. Our results indicate that the majority of the detected elements were distributed in liver, kidney, pelt, turnout while a small fraction of the biotrace elements were distributed in heart and spleen. (tumour-bearing mice) in the two groups of mice. The higher concentrations of Fe, Na, Mn were detected in heart or kidney of normal mice. Na, Mn, Fe and Co showed better absorption in most tissues in the normal mice, except for Na and Mn in heart. (authors)

Universal design of a microcontroller and IoT system to detect the heart rate

Science.gov (United States)

Uwamahoro, Raphael; Mushikiwabeza, Alexie; Minani, Gerard; Mohan Murari, Bhaskar

2017-11-01

Heart rate analysis provides vital information of the present condition of the human body. It helps medical professionals in diagnosis of various malfunctions of the body. The limitation of vision impaired and blind people to access medical devices cause a considerable loss of life. In this paper, we intended to develop a heart rate detection system that is usable for people with normal and abnormal vision. The system is based on a non-invasive method of measuring the variation of the tissue blood flow rate by means of a photo transmitter and detector through fingertip known as photoplethysmography (PPG). The signal detected is firstly passed through active low pass filter and then amplified by a two stages high gain amplifier. The amplified signal is feed into the microcontroller to calculate the heart rate and displays the heart beat via sound systems and Liquid Crystal Display (LCD). To distinguish arrhythmia, normal heart rate and abnormal working conditions of the system, recognition is provided in different sounds, LCD readings and Light Emitting Diodes (LED).

Heart Health - Brave Heart

Science.gov (United States)

... Bar Home Current Issue Past Issues Cover Story Heart Health Brave Heart Past Issues / Winter 2009 Table of Contents For ... you can have a good life after a heart attack." Lifestyle Changes Surviving—and thriving—after such ...

Characterizing Gaseous Fuels for Their Knock Resistance based on the Chemical and Physical Properties of the Fuel

NARCIS (Netherlands)

Levinsky, Howard; Gersen, Sander; van Essen, Martijn; van Dijk, Gerco

2016-01-01

A method is described to characterize the effects of changes in the composition of gaseous fuels on engine knock by computing the autoignition process during the compression and burn periods of the engine cycle. To account for the effects of fuel composition on the in-cylinder pressure and

Energy dependence of the cross section of fast deuteron knock-out from Li, Be, and C by 380 to 665 MeV protons

Energy Technology Data Exchange (ETDEWEB)

Komarov, V I; Kosarev, G E; Reshetnikov, G P; Savchenko, O V; Tesh, Z

1974-12-31

The high energy parts of the spectra of fast deuterons, which are knocked out from Li, Be and C targets by protons at a 5.5 deg lab. angle with proton energies of 666, 578, 484 and 382 MeV were measured. The cross sections of quasi-elastic deuteron knock-out obtained are compared with the corresponding cross sections of elastic pd-scattering at energies mentioned above. The evaluations of the effective number of two-nucleon clusters are discussed, which have been obtained taking into account (in the Glauber approximation) the incident proton and knocked-out deuteron interactions with nuclear nucleons. The results show the common behavior of the scattering mechanism responsible for elastic pd- and quasi-elastic proton backward scattering with large momentum transfer to two-nucleon clusters. The energy dependence of the deuteron production cross section at the energy kinematically corresponding to the p + N yields d + pi process on tanget nucleons is close to that of the cross section for the p + p yields d + pi /sup +/ process. (auth)

Adrenergic innervation of the developing chick heart: neural crest ablations to produce sympathetically aneural hearts

International Nuclear Information System (INIS)

Kirby, M.; Stewart, D.

1984-01-01

Ablation of various regions of premigratory trunk neural crest which gives rise to the sympathetic trunks was used to remove sympathetic cardiac innervation. Neuronal uptake of [ 3 H]-norepinephrine was used as an index of neuronal development in the chick atrium. Following ablation of neural crest over somites 10-15 or 15-20, uptake was significantly decreased in the atrium at 16 and 17 days of development. Ablation of neural crest over somites 5-10 and 20-25 caused no decrease in [ 3 H]-norepinephrine uptake. Removal of neural crest over somites 5-25 or 10-20 caused approximately equal depletions of [ 3 H]-norepinephrine uptake in the atrium. Cardiac norepinephrine concentration was significantly depressed following ablation of neural crest over somites 5-25 but not over somites 10-20. Light-microscopic and histofluorescent preparations confirmed the absence of sympathetic trunks in the region of the normal origin of the sympathetic cardiac nerves following neural crest ablation over somites 10-20. The neural tube and dorsal root ganglia were damaged in the area of the neural-crest ablation; however, all of these structures were normal cranial and caudal to the lesioned area. Development of most of the embryos as well as the morphology of all of the hearts was normal following the lesion. These results indicate that it is possible to produce sympathetically aneural hearts by neural-crest ablation; however, sympathetic cardiac nerves account for an insignificant amount of cardiac norepinephrine

Rest thallium-201 myocardial perfusion imaging in a patient with leukaemic infiltration of the heart

International Nuclear Information System (INIS)

Civelek, A.C.; Camargo, E.E.; Links, J.M.; Brinker, J.A.; Wagner, H.N. Jr.

1992-01-01

Despite the high incidence of leukaemic infiltration of the heart, only 8 cases of atrioventricular block due to leukemia have been reported in the literature. Improvement in the heart block associated with disappearance of the leukaemic infiltrate has not been reported. A rest thallium-201 study was used in a 65-year-old man to demonstrate leukaemic infiltration of the heart which was associated with complete heart block. After chemotherapy, when the tumour burden was reduced and the leukaemia in remission, his heart block resolved, and a follow-up thallium scan was normal. (orig.)

Heart transplantation and arterial elasticity

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Colvin-Adams M

2013-12-01

Full Text Available Monica Colvin-Adams,1 Nonyelum Harcourt,1 Robert LeDuc,2 Ganesh Raveendran,1 Yassir Sonbol,3 Robert Wilson,1 Daniel Duprez11Cardiovascular Division, University of Minnesota, Minneapolis, MN, USA; 2Division of Biostatistics University of Minnesota, Minneapolis, MN, USA; 3Cardiovascular Division, St Luke's Hospital System, Sugar Land, TX, USAObjective: Arterial elasticity is a functional biomarker that has predictive value for cardiovascular morbidity and mortality in nontransplant populations. There is little information regarding arterial elasticity in heart transplant recipients. This study aimed to characterize small (SAE and large (LAE artery elasticity in heart transplant recipients in comparison with an asymptomatic population free of overt cardiovascular disease. A second goal was to identify demographic and clinical factors associated with arterial elasticity in this unique population.Methods: Arterial pulse waveform was registered noninvasively at the radial artery in 71 heart transplant recipients between 2008 and 2010. SAEs and LAEs were derived from diastolic pulse contour analysis. Comparisons were made to a healthy cohort of 1,808 participants selected from our prevention clinic database. Multiple regression analyses were performed to evaluate associations between risk factors and SAE and LAE within the heart transplant recipients.Results: LAE and SAE were significantly lower in heart transplant recipients than in the normal cohort (P <0.01 and P < 0.0001, respectively. Female sex and history of ischemic cardiomyopathy were significantly associated with reduced LAE and SAE. Older age and the presence of moderate cardiac allograft vasculopathy were also significantly associated with reduced SAE. Transplant duration was associated with increased SAE.Conclusion: Heart transplants are associated with peripheral endothelial dysfunction and arterial stiffness, as demonstrated by a significant reduction in SAE and LAE when compared with a

Chest radiographic findings and complications of the temporary implantation of the Jarvik-7 artificial heart while awaiting orthotopic heart transplantation: Experience with five cases

International Nuclear Information System (INIS)

Sadler, L.R.; Fuhrman, C.R.; Hardesty, R.A.; Griffith, B.P.

1986-01-01

The Jarvik-7 artificial heart was originally introduced as a therapeutic alternative to cardiac transplantation in patients with endstage refractory cardiac disease. Its use has been expanded to those patients awaiting cardiac transplantation in whom death is impending and for whom a suitable donor match is unavailable. At Presbyterian-University Hospital of Pittsburgh five patients have had Jarvik-7 hearts implanted as a temporary measure while awaiting compatible donors for cardiac transplantation. The authors believe this is the largest patient group to undergo this procedure at a single institution. They present a brief description of the Jarvik-7 heart, the clinical factors affecting patient selection, and the radiographic appearance of a normally functioning Jarvik-7 heart, and review the chest radiographic complications seen in the patient group, along with eventual patient outcome

Prior publication productivity, grant percentile ranking, and topic-normalized citation impact of NHLBI cardiovascular R01 grants.

Science.gov (United States)

Kaltman, Jonathan R; Evans, Frank J; Danthi, Narasimhan S; Wu, Colin O; DiMichele, Donna M; Lauer, Michael S

2014-09-12

We previously demonstrated absence of association between peer-review-derived percentile ranking and raw citation impact in a large cohort of National Heart, Lung, and Blood Institute cardiovascular R01 grants, but we did not consider pregrant investigator publication productivity. We also did not normalize citation counts for scientific field, type of article, and year of publication. To determine whether measures of investigator prior productivity predict a grant's subsequent scientific impact as measured by normalized citation metrics. We identified 1492 investigator-initiated de novo National Heart, Lung, and Blood Institute R01 grant applications funded between 2001 and 2008 and linked the publications from these grants to their InCites (Thompson Reuters) citation record. InCites provides a normalized citation count for each publication stratifying by year of publication, type of publication, and field of science. The coprimary end points for this analysis were the normalized citation impact per million dollars allocated and the number of publications per grant that has normalized citation rate in the top decile per million dollars allocated (top 10% articles). Prior productivity measures included the number of National Heart, Lung, and Blood Institute-supported publications each principal investigator published in the 5 years before grant review and the corresponding prior normalized citation impact score. After accounting for potential confounders, there was no association between peer-review percentile ranking and bibliometric end points (all adjusted P>0.5). However, prior productivity was predictive (Pcitation counts, we confirmed a lack of association between peer-review grant percentile ranking and grant citation impact. However, prior investigator publication productivity was predictive of grant-specific citation impact. © 2014 American Heart Association, Inc.

ABCC-NIH adult health study, Hiroshima 1958-1960. Cardiovascular project report Number 6, heart size norm

Energy Technology Data Exchange (ETDEWEB)

Ueda, Shoichi, Russell, W.J.; Yano, Katsuhiko

1962-05-01

Utilizing the information obtained from the detailed clinical examinations of subjects seen at the Atomic Bomb Casualty Commission, standard heart size determinations in the Hiroshima population are provided. A formula has been devised to express the normal transverse cardiac diameter, obtained from the routine posteroanterior chest roentgenogram, in relation to weight, height, and age. The analysis was made for each sex separately. Values computed by using this formula are regarded as standard heart size. Deviations from the standard are interpreted as individual variability in the normal group, with a standard deviation of 9 mm. When this standard was applied to abnormal subjects, a high correlation between the relative heart size and the blood pressure or the presence of overt heart disease was evident. For this reason, the relative heart size for this standard should prove useful, together with other related factors, in the diagnosis and investigation of cardiovascular disease. A nomograph has been devised for practical use. 12 references, 7 figures, 4 tables.

Nutrition in neonatal congenital heart disease

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Morgan CT

2013-09-01

Full Text Available Conall T Morgan,1 Anne Marie Shine,2 Colin J McMahon1 1Department of Pediatric Cardiology, 2Department of Clinical Nutrition and Dietetics, Our Lady's Children's Hospital Crumlin, Dublin, Republic of Ireland Abstract: There are 40,000 infants born in the USA with congenital heart disease annually. Achievement of adequate oral nutrition is difficult in this population. Malnutrition is common. Single ventricle physiology, the risk of necrotizing enterocolitis, and cardiopulmonary bypass prevent the establishment of normal oral feeding patterns. Improved nutrition results in improved surgical outcomes, lower mortality, and shorter hospital stay. In this review, we discuss the challenges this population faces. Keywords: necrotizing enterocolitis, malnutrition, growth failure, hypoplastic left heart

A new knock-in mouse model of l-DOPA-responsive dystonia.

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Rose, Samuel J; Yu, Xin Y; Heinzer, Ann K; Harrast, Porter; Fan, Xueliang; Raike, Robert S; Thompson, Valerie B; Pare, Jean-Francois; Weinshenker, David; Smith, Yoland; Jinnah, Hyder A; Hess, Ellen J

2015-10-01

Abnormal dopamine neurotransmission is associated with many different genetic and acquired dystonic disorders. For instance, mutations in genes critical for the synthesis of dopamine, including GCH1 and TH cause l-DOPA-responsive dystonia. Despite evidence that implicates abnormal dopamine neurotransmission in dystonia, the precise nature of the pre- and postsynaptic defects that result in dystonia are not known. To better understand these defects, we generated a knock-in mouse model of l-DOPA-responsive dystonia (DRD) mice that recapitulates the human p.381Q>K TH mutation (c.1141C>A). Mice homozygous for this mutation displayed the core features of the human disorder, including reduced TH activity, dystonia that worsened throughout the course of the active phase, and improvement in the dystonia in response to both l-DOPA and trihexyphenidyl. Although the gross anatomy of the nigrostriatal dopaminergic neurons was normal in DRD mice, the microstructure of striatal synapses was affected whereby the ratio of axo-spinous to axo-dendritic corticostriatal synaptic contacts was reduced. Microinjection of l-DOPA directly into the striatum ameliorated the dystonic movements but cerebellar microinjections of l-DOPA had no effect. Surprisingly, the striatal dopamine concentration was reduced to ∼1% of normal, a concentration more typically associated with akinesia, suggesting that (mal)adaptive postsynaptic responses may also play a role in the development of dystonia. Administration of D1- or D2-like dopamine receptor agonists to enhance dopamine signalling reduced the dystonic movements, whereas administration of D1- or D2-like dopamine receptor antagonists to further reduce dopamine signalling worsened the dystonia, suggesting that both receptors mediate the abnormal movements. Further, D1-dopamine receptors were supersensitive; adenylate cyclase activity, locomotor activity and stereotypy were exaggerated in DRD mice in response to the D1-dopamine receptor agonist SKF

Total Artificial Heart Implantation as a Bridge to Heart Transplantation in an Active Duty Service Member With Amyloid Cardiomyopathy.

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Scully, Michael S; Wessman, Dylan E; McKee, James M; Francisco, Gregory M; Nayak, Keshav R; Kobashigawa, Jon A

2017-03-01

Cardiac involvement by light-chain (AL) amyloid occurs in up to 50% of patients with primary AL amyloidosis. The prognosis of amyloid heart disease is poor with 1-year survival rates of 35 to 40%. Historically, heart transplantation was considered controversial for patients with AL amyloid cardiomyopathy (CM) given the systemic nature of the disease and poor survival. We present a case report of an active duty service member diagnosed with advanced cardiac amyloid who underwent total artificial heart transplant as a bridge to heart transplant and eventual autologous stem cell transplant. A 47-year-old active duty male initially evaluated for atypical chest pain was found to have severe concentric left ventricular hypertrophy on echocardiogram but normal voltage on electrocardiogram. Cardiac magnetic resonance imaging, laboratory studies, and bone marrow biopsy established the diagnosis of cardiac amyloidosis. At the time of diagnosis, the patient's prognosis was very poor with a median survival of 5 months on the basis of the Mayo Clinic revised prognostic staging system for amyloidosis. The patient developed rapidly progressive left ventricular dysfunction and heart failure leading to cardiac arrest. The patient received a total artificial heart as a bridge to orthotopic heart and kidney transplantation and eventual stem cell transplant. He continues to be in remission and has a fair functional capacity without restriction in activities of daily living or moderate exercise. Amyloid CM is a rare and devastating disease. The natural course of the disease has made heart transplant in these patients controversial. Modern advancements in chemotherapies and advanced heart failure treatments have improved outcomes for select patients with AL amyloid CM undergoing heart transplantation. There is ongoing research seeking improvement in treatment options and outcomes for patients with this deadly disease. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Ventricular arrhythmias in the absence of structural heart disease.

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Prystowsky, Eric N; Padanilam, Benzy J; Joshi, Sandeep; Fogel, Richard I

2012-05-15

Ventricular arrhythmia (VA) in structurally normal hearts can be broadly considered under non-life-threatening monomorphic and life-threatening polymorphic rhythms. Monomorphic VA is classified on the basis of site of origin in the heart, and the most common areas are the ventricular outflow tracts and left ventricular fascicles. The morphology of the QRS complexes on electrocardiogram is an excellent tool to identify the site of origin of the rhythm. Although these arrhythmias are common and generally carry an excellent prognosis, rare sudden death events have been reported. Very frequent ventricular ectopy may also result in a cardiomyopathy in a minority of patients. Suppression of VA may be achieved using calcium-channel blockers, beta-adrenergic blockers, and class I or III antiarrhythmic drugs. Radiofrequency ablation has emerged as an excellent option to eliminate these arrhythmias, although certain foci including aortic cusps and epicardium may be technically challenging. Polymorphic ventricular tachycardia (VT) is rare and generally occurs in patients with genetic ion channel disorders including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic VT, and short QT syndrome. Unlike monomorphic VT, these arrhythmic syndromes are associated with sudden death. While the cardiac gross morphology is normal, suggesting a structurally normal heart, abnormalities exist at the molecular level and predispose them to arrhythmias. Another fascinating area, idiopathic ventricular fibrillation and early repolarization syndrome, are undergoing research for a genetic basis. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Pet measurements of presynaptic sympathetic nerve terminals in the heart

International Nuclear Information System (INIS)

Schwaiger, M.; Hutchins, G.D.; Wieland, D.M.

1991-01-01

[ 18 F]Metaraminol (FMR) and [ 11 C]hydroxyephedrine (HED) are catecholamine analogues that have been developed at the University of Michigan for the noninvasive characterization of the sympathetic nervous system of the heart using positron emission tomography (PET). Pharmacological studies employing neurotoxins and uptake inhibitors have demonstrated that both FMR and HED specifically trace the uptake and storage of catecholamines in sympathetic nerve terminals with little nonspecific tracer accumulation. These compounds exhibit excellent qualitative imaging characteristics with heart-to-blood ratios exceeding 6:1 as early as 15 min after intravenous injection in both animals (HED and FMR) and humans (HED). Tracer kinetic modeling techniques have been employed for the quantitative assessment of neuronal catecholamine uptake and storage. Indices of neuronal function, such as the volume of tracer distribution derived from the kinetic models, have been employed in preliminary human studies. Comparison of the tissue distribution volume of HED between normal (control subjects) and denervated (recent transplant patients) cardiac tissue demonstrates a dynamic range of approximately 5:1. This distribution volume is reduced by 60% from normal in patients with dilated cardiomyopathy, indicating dysfunction of the sympathetic system. These results show that HED used in combination with PET provides a sophisticated quantitative approach for studying the sympathetic nervous system of the normal and diseased human heart

Heart rate turbulence and variability in patients with ventricular arrhythmias

Directory of Open Access Journals (Sweden)

Diego Tarricone

2009-08-01

Full Text Available Background: To evaluate the changes in autonomic neural control mechanisms before malignant ventricular arrhythmias, we measured heart rate variability (HRV and heart rate turbulence (HRT in patients with ventricular tachycardia or fibrillation (Group I; n=6, non sustained ventricular tachycardia (Group II; n=32, frequent premature ventricular beats (Group III; n=26 and with ICD implantation (Group IV; n=11. Methods: Time domain parameters of HRV and turbulence onset (TO and slope (TS were calculated on 24 hour Holter recordings. Normal values were: SDNN > 70 msec for HRV, TO <0% and TS >2.5 msec/RR-I for HRT. Results: Whereas SDNN was within normal range and similar in all study groups, HRT parameters were significantly different in patients who experienced VT/VF during Holter recording. Abnormal TO and/or TS were present in 100% of Group I patients and only in about 50% of Group II and IV. On the contrary, normal HRT parameters were present in 40-70% of Group II, III and IV patients and none of Group I. Conclusions: These data suggest that HRT analysis is more suitable than HRV to detect those transient alterations in autonomic control mechanisms that are likely to play a major trigger role in the genesis of malignant cardiac arrhythmias. (Heart International 2007; 3: 51-7

Effects of SIRT1 gene knock-out via activation of SREBP2 protein-mediated PI3K/AKT signaling on osteoarthritis in mice.

Science.gov (United States)

Yu, Fei; Zeng, Hui; Lei, Ming; Xiao, De-Ming; Li, Wei; Yuan, Hao; Lin, Jian-Jing

2016-10-01

This study investigated the effects of SIRT1 gene knock-out on osteoarthritis in mice, and the possible roles of SREBP2 protein and the PI3K/AKT signaling pathway in the effects. Mice were randomly divided into a normal group and a SIRT1 gene knock-out group (6 mice in each group). In these groups, one side of the knee anterior cruciate ligament was traversed, and the ipsilateral medial meniscus was cut to establish an osteoarthritis model of knee joint. The countralateral synovial bursa was cut out, serving as controls. The knee joint specimens were then divided into four groups: SIRT1 +/+ control group (group A, n=6); SIRT1 +/+ osteoarthritis group (group B, n=6); SIRT1 -/- control group (group C, n=6); SIRT1 -/- osteoarthritis group (group D, n=6). HE staining, Masson staining, Safranin O-Fast Green staining and Van Gieson staining were used to observe the morphological changes in the articular cartilage of the knee. Immunohistochemical staining was employed to detect the expression of SIRT1, SREBP2, VEGF, AKT, HMGCR and type II collagen proteins. SA-β-gal staining was utilized to evaluate chondrocyte aging. The results showed clear knee joint cartilage destruction and degeneration in the SIRT1 -/- osteoarthritis group. The tidal line was twisted and displaced anteriorly. Type II collagen was destroyed and distributed unevenly. Compared with the SIRT1 +/+ osteoarthritis group and SIRT1 -/- control group, SIRT1 protein expression was not obviously changed in the SIRT1 -/- osteoarthritis group (P>0.05), while the expression levels of the SREBP2, VEGF and HMGCR proteins were significantly increased (Pknock-out may aggravate cartilage degeneration in osteoarthritis by activating the SREBP2 protein-mediated PI3K/AKT signalling pathway, suggesting that SIRT1 gene may play a protective role against osteoarthritis.

Targeted knock-in of CreER T2 in zebrafish using CRISPR/Cas9.

Science.gov (United States)

Kesavan, Gokul; Hammer, Juliane; Hans, Stefan; Brand, Michael

2018-04-01

New genome-editing approaches, such as the CRISPR/Cas system, have opened up great opportunities to insert or delete genes at targeted loci and have revolutionized genetics in model organisms like the zebrafish. The Cre-loxp recombination system is widely used to activate or inactivate genes with high spatial and temporal specificity. Using a CRISPR/Cas9-mediated knock-in strategy, we inserted a zebrafish codon-optimized CreER T2 transgene at the otx2 gene locus to generate a conditional Cre-driver line. We chose otx2 as it is a patterning gene of the anterior neural plate that is expressed during early development. By knocking in CreER T2 upstream of the endogenous ATG of otx2, we utilized this gene's native promoter and enhancer elements to perfectly match CreER T2 and endogenous otx2 expression patterns. Next, by combining this novel driver line with a Cre-dependent reporter line, we show that only in the presence of tamoxifen can efficient Cre-loxp-mediated recombination be achieved in the anterior neural plate-derived tissues like the telencephalon, the eye and the optic tectum. Our results imply that the otx2:CreER T2 transgenic fish will be a valuable tool for lineage tracing and conditional mutant studies in larval and adult zebrafish.

Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual Disability Cereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein Kinase-mTORC1 Translational Pathway.

Science.gov (United States)

Bavley, Charlotte C; Rice, Richard C; Fischer, Delaney K; Fakira, Amanda K; Byrne, Maureen; Kosovsky, Maria; Rizzo, Bryant K; Del Prete, Dolores; Alaedini, Armin; Morón, Jose A; Higgins, Joseph J; D'Adamio, Luciano; Rajadhyaksha, Anjali M

2018-03-14

A homozygous nonsense mutation in the cereblon ( CRBN ) gene results in autosomal recessive, nonsyndromic intellectual disability that is devoid of other phenotypic features, suggesting a critical role of CRBN in mediating learning and memory. In this study, we demonstrate that adult male Crbn knock-out ( Crbn KO ) mice exhibit deficits in hippocampal-dependent learning and memory tasks that are recapitulated by focal knock-out of Crbn in the adult dorsal hippocampus, with no changes in social or repetitive behavior. Cellular studies identify deficits in long-term potentiation at Schaffer collateral CA1 synapses. We further show that Crbn is robustly expressed in the mouse hippocampus and Crbn KO mice exhibit hyperphosphorylated levels of AMPKα (Thr172). Examination of processes downstream of AMP-activated protein kinase (AMPK) finds that Crbn KO mice have a selective impairment in mediators of the mTORC1 translation initiation pathway in parallel with lower protein levels of postsynaptic density glutamatergic proteins and higher levels of excitatory presynaptic markers in the hippocampus with no change in markers of the unfolded protein response or autophagy pathways. Acute pharmacological inhibition of AMPK activity in adult Crbn KO mice rescues learning and memory deficits and normalizes hippocampal mTORC1 activity and postsynaptic glutamatergic proteins without altering excitatory presynaptic markers. Thus, this study identifies that loss of Crbn results in learning, memory, and synaptic defects as a consequence of exaggerated AMPK activity, inhibition of mTORC1 signaling, and decreased glutamatergic synaptic proteins. Thus, Crbn KO mice serve as an ideal model of intellectual disability to further explore molecular mechanisms of learning and memory. SIGNIFICANCE STATEMENT Intellectual disability (ID) is one of the most common neurodevelopmental disorders. The cereblon ( CRBN ) gene has been linked to autosomal recessive, nonsyndromic ID, characterized by an

A Low-Normal Free Triiodothyronine Level Is Associated with Adverse Prognosis in Euthyroid Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

Science.gov (United States)

Chen, Yu-Yang; Shu, Xiao-Rong; Su, Zi-Zhuo; Lin, Rong-Jie; Zhang, Hai-Feng; Yuan, Wo-Liang; Wang, Jing-Feng; Xie, Shuang-Lun

2017-12-12

Thyroid dysfunction is prevalent in patients with heart failure (HF) and hypothyroidism is related to the adverse prognosis of HF subjects receiving cardiac resynchronization therapy (CRT). We aim to investigate whether low-normal free triiodothyronine (fT3) level is related to CRT response and the prognosis of euthyroid patients with HF after CRT implantation.One hundred and thirteen euthyroid patients who received CRT therapy without previous thyroid disease and any treatment affecting thyroid hormones were enrolled. All of patients were evaluated for cardiac function and thyroid hormones (serum levels of fT3, free thyroxine [fT4] and thyroid-stimulating hormone [TSH]). The end points were overall mortality and hospitalization for HF worsening. During a follow-up period of 39 ± 3 weeks, 36 patients (31.9%) died and 45 patients (39.8%) had hospitalization for HF exacerbation. A higher rate of NYHA III/IV class and a lower fT3 level were both observed in death group and HF event group. Multivariate Cox regression analyses disclosed that a lower-normal fT3 level (HR = 0.648, P = 0.009) and CRT response (HR = 0.441, P = 0.001) were both independent predictors of overall mortality. In addition, they were also both related to HF re-hospitalization event (P < 0.01 for both). Patients with fT3 < 3.00 pmol/L had a significantly higher overall mortality than those with fT3 ≥ 3.00 pmol/L (P = 0.027). Meanwhile, a higher HF hospitalization event rate was also found in patients with fT3 < 3.00 pmol/L (P < 0.001).A lower-normal fT3 level is correlated with a worse cardiac function an adverse prognosis in euthyroid patients with HF after CRT implantation.

Using impedance cardiography to assess left ventricular systolic function via postural change in patients with heart failure.

Science.gov (United States)

DeMarzo, Arthur P; Calvin, James E; Kelly, Russell F; Stamos, Thomas D

2005-01-01

For the diagnosis and management of heart failure, it would be useful to have a simple point-of-care test for assessing ventricular function that could be performed by a nurse. An impedance cardiography (ICG) parameter called systolic amplitude (SA) can serve as an indicator of left ventricular systolic function (LVSF). This study tested the hypothesis that patients with normal LVSF should have a significant increase in SA in response to an increase in end-diastolic volume caused by postural change from sitting upright to supine, while patients with depressed LVSF associated with heart failure should have a minimal increase or a decrease in SA from upright to supine. ICG data were obtained in 12 patients without heart disease and with normal LVSF and 18 patients with clinically diagnosed heart failure. Consistent with the hypothesis, patients with normal LVSF had a significant increase in SA from upright to supine, whereas heart failure patients had a minimal increase or a decrease in SA from upright to supine. This ICG procedure may be useful for monitoring the trend of patient response to titration of beta blockers and other medications. ICG potentially could be used to detect worsening LVSF and provide a means of measurement for adjusting treatment.

NPHP4 Variants Are Associated With Pleiotropic Heart Malformations

NARCIS (Netherlands)

French, Vanessa M.; van de Laar, Ingrid M. B. H.; Wessels, Marja W.; Rohe, Christan; Roos-Hesselink, Jolien W.; Wang, Guangliang; Frohn-Mulder, Ingrid M. E.; Severijnen, Lies-Anne; de Graaf, Bianca M.; Schot, Rachel; Breedveld, Guido; Mientjes, Edwin; van Tienhoven, Marianne; Jadot, Elodie; Jiang, Zhengxin; Verkerk, Annemieke; Swagemakers, Sigrid; Venselaar, Hanka; Rahimi, Zohreh; Najmabadi, Hossein; Meijers-Heijboer, Hanne; de Graaff, Esther; Helbing, Wim A.; Willemsen, Rob; Devriendt, Koen; Belmont, John W.; Oostra, Ben A.; Amack, Jeffrey D.; Bertoli-Avella, Aida M.

2012-01-01

Rationale: Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs. Objective: To identify genetic

NPHP4 variants are associated with pleiotropic heart malformations.

NARCIS (Netherlands)

French, V.M.; Laar, I.M. van de; Wessels, M.W.; Rohe, C.; Roos-Hesselink, J.W.; Wang, G.; Frohn-Mulder, I.M.; Severijnen, L.A.; Graaf, B.M. de; Schot, R.; Breedveld, G.; Mientjes, E.; Tienhoven, M. van; Jadot, E.; Jiang, Z.; Verkerk, A.; Swagemakers, S.; Venselaar, H.; Rahimi, Z.; Najmabadi, H.; Meijers-Heijboer, H.; Graaff, E. de; Helbing, W.A.; Willemsen, R.; Devriendt, K.; Belmont, J.W.; Oostra, B.A.; Amack, J.D.; Bertoli-Avella, A.M.

2012-01-01

RATIONALE: Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs. OBJECTIVE: To identify genetic

Using CRISPR/Cas9 to Knock out Amylase in Acinar Cells Decreases Pancreatitis-Induced Autophagy

Directory of Open Access Journals (Sweden)

Kohei Yasunaga

2018-01-01

Full Text Available Pancreatic cancer is a malignant neoplasm that originates from acinar cells. Acinar cells get reprogrammed to become duct cells, resulting in pancreatic cancer. Pancreatitis is an acinar cell inflammation, leading to “impaired autophagy flux”. Pancreatitis promotes acinar-to-ductal transdifferentiation. Expression of amylase gets eliminated during the progression of pancreatic cancer. Amylase is considered as an acinar cell marker; however, its function in cells is not known. Thus, we investigated whether amylase affects the acinar cell autophagy and whether it plays any role in development of pancreatitis. Here, we knocked out ATG12 in a pancreatic cancer cells and acinar cells using CRISPR/Cas9. Autophagy inhibition led to an increase in the expression of duct cell markers and a simultaneous decrease in that of acinar cell markers. It also caused an increase in cell viability and changes in mitochondrial morphology. Next, we knocked out amylase in acinar cells. Amylase deficiency decreased autophagy induced by pancreatitis. Our results suggest that amylase controls pancreatitis-induced autophagy. We found that eliminating amylase expression contributes to pancreatic cancer etiology by decreasing autophagy. Furthermore, our results indicate that amylase plays a role in selective pancreatitis-induced autophagy of pancreatic enzyme vesicles.

Increased heart rate variability but normal resting metabolic rate in hypocretin/orexin-deficient human narcolepsy.

NARCIS (Netherlands)

Fronczek, R.; Overeem, S.; Reijntjes, R.; Lammers, G.J.; Dijk, J.G.M.; Pijl, H.

2008-01-01

STUDY OBJECTIVES: We investigated autonomic balance and resting metabolic rate to explore their possible involvement in obesity in hypocretin/orexin-deficient narcoleptic subjects. METHODS: Resting metabolic rate (using indirect calorimetry) and variability in heart rate and blood pressure were

Plasma intermedin concentration in patients with chronic heart faliure

International Nuclear Information System (INIS)

Yu Xiaohua; Du Xingbang; Zhu Yunhe; Luo Lei; Zhao Changjun; Liu Yongfeng; Ren Liangping; Ren Yongsheng

2011-01-01

Objective: To study the clinical significance of determination of changes of plasma levels of intermedin (IMD), BNP and CRP in patients with chronic heart failure. Methods: Plasma IMD, BNP (with RIA) and CRP (with immuno-turbidity) levels were determined in 46 patients with chronic heart failure of various grades (grade I-II n=31, grade III-IV, n=15) and 42 normal controls. Results: Compared with the control group,the plasma IMD level in patients with chronic heart failure was decreased 53.2% (P<0.01), the BNP and CRP were increased 1658.5% and 80.5% respectively (each P<0.001). Compared with the grade I-II group, the plasma IMD level in grade III-IV was decreased 34.7% (P<0.05), the BNP and CRP levels in grade III-IV were increased 257.8% and 76% (all P<0.001) individually. Conclusion: Plasma intermedin concentration was significantly decreased in patients with chronic heart failure, which suggests that they play an important role in the pathogenesis of chronic heart failure. (authors)

Study on the abnormal morphogenesis of the arterial end of the heart induced by neutron irradiation

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Hidaka, N [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

1980-02-01

Transposition complexes of the great arteries were frequently produced in rat embryonic hearts whose mothers were exposed to a single whole-body dose of 130 rad 14.1 MeV fast neutron radiation on 8 day after conception. To clarify the morphogenesis of transposition complexes, especially double outlet right ventricle (DORV), embryonic rat hearts were serially sectioned and were reconstructed photographically 13 to 16 days after conception, when truncal swelling, intercalated valve swelling, and conical ridges appeared. In the control group, all the hearts had a normal D (dextral) loop. In the experimental group, 82.6% of the hearts had a D loop, 11.3% had an L (levo) loop, and 5.9% had an A (anterior) loop. In this group, the D loop hearts were divided into normal, retarded, and abnormal. Most of the retarded hearts developed into abnormal hearts. The positional relationships between experimentally produced swelling and ridges are classified. Morphologic anomalies are formed in the truncoconal region and correspond to the site of and the quantitative changes of the swelling and ridges. Abnormality in the position and extent of the swelling and ridges is the most important characteristic in the morphogenesis of transposition complexes. The second most important characteristic is abnormality in the time of appearance and the extent and site of cell death in the conical septum. DORV is embryologically divided into two types: a type in which the great arteries are normally related and a type in which they are inversely related. The developmental process of the DORV is entirely different from that of the complete transposition of the great arteries.

The human heart: application of the golden ratio and angle.

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Henein, Michael Y; Zhao, Ying; Nicoll, Rachel; Sun, Lin; Khir, Ashraf W; Franklin, Karl; Lindqvist, Per

2011-08-04

The golden ratio, or golden mean, of 1.618 is a proportion known since antiquity to be the most aesthetically pleasing and has been used repeatedly in art and architecture. Both the golden ratio and the allied golden angle of 137.5° have been found within the proportions and angles of the human body and plants. In the human heart we found many applications of the golden ratio and angle, in addition to those previously described. In healthy hearts, vertical and transverse dimensions accord with the golden ratio, irrespective of different absolute dimensions due to ethnicity. In mild heart failure, the ratio of 1.618 was maintained but in end-stage heart failure the ratio significantly reduced. Similarly, in healthy ventricles mitral annulus dimensions accorded with the golden ratio, while in dilated cardiomyopathy and mitral regurgitation patients the ratio had significantly reduced. In healthy patients, both the angles between the mid-luminal axes of the pulmonary trunk and the ascending aorta continuation and between the outflow tract axis and continuation of the inflow tract axis of the right ventricle approximate to the golden angle, although in severe pulmonary hypertension, the angle is significantly increased. Hence the overall cardiac and ventricular dimensions in a normal heart are consistent with the golden ratio and angle, representing optimum pump structure and function efficiency, whereas there is significant deviation in the disease state. These findings could have anatomical, functional and prognostic value as markers of early deviation from normality. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A comparison of single knock-on and complete bubble destruction models of the fission induced re-solution of gas atoms from bubbles

International Nuclear Information System (INIS)

Wood, M.H.

1978-03-01

In previous theoretical studies of the behaviour of the fission gases in nuclear fuel, the Nelson single knock-on model of the fission induced re-solution of gas atoms from fission gas bubbles has been employed. In the present investigation, predictions from this model are compared with those from a complete bubble destruction model of the re-solution process. The main conclusions of the study are that the complete bubble destruction model predicts more gas release after a particular irradiation time than the single knock-on model, for the same choice of the model parameters, and that parameter sets chosen to give the same gas release predict significantly different bubble size distribution functions. (author)

The role of abnormal fetal heart rate in scheduling chorionic villus sampling.

Science.gov (United States)

Yagel, S; Anteby, E; Ron, M; Hochner-Celnikier, D; Achiron, R

1992-09-01

To assess the value of fetal heart rate (FHR) measurements in predicting spontaneous fetal loss in pregnancies scheduled for chorionic villus sampling (CVS). A prospective descriptive study. Two hospital departments of obstetrics and gynaecology in Israel. 114 women between 9 and 11 weeks gestation scheduled for chorionic villus sampling (CVS). Fetal heart rate was measured by transvaginal Doppler ultrasound and compared with a monogram established from 75 fetuses. Whenever a normal FHR was recorded, CVS was performed immediately. 106 women had a normal FHR and underwent CVS; two of these pregnancies ended in miscarriage. In five pregnancies no fetal heart beats could be identified and fetal death was diagnosed. In three pregnancies an abnormal FHR was recorded and CVS was postponed; all three pregnancies ended in miscarriage within 2 weeks. Determination of FHR correlated with crown-rump length could be useful in predicting spontaneous miscarriage before performing any invasive procedure late in the first trimester.

Ivabradine Improves Heart Rate Variability in Patients with Nonischemic Dilated Cardiomyopathy

Directory of Open Access Journals (Sweden)

Ertugrul Kurtoglu

2014-10-01

Full Text Available Background: Ivabradine is a novel specific heart rate (HR-lowering agent that improves event-free survival in patients with heart failure (HF. Objectives: We aimed to evaluate the effect of ivabradine on time domain indices of heart rate variability (HRV in patients with HF. Methods: Forty-eight patients with compensated HF of nonischemic origin were included. Ivabradine treatment was initiated according to the latest HF guidelines. For HRV analysis, 24-h Holter recording was obtained from each patient before and after 8 weeks of treatment with ivabradine. Results: The mean RR interval, standard deviation of all normal to normal RR intervals (SDNN, the standard deviation of 5-min mean RR intervals (SDANN, the mean of the standard deviation of all normal-to-normal RR intervals for all 5-min segments (SDNN index, the percentage of successive normal RR intervals exceeding 50 ms (pNN50, and the square root of the mean of the squares of the differences between successive normal to normal RR intervals (RMSSD were low at baseline before treatment with ivabradine. After 8 weeks of treatment with ivabradine, the mean HR (83.6 ± 8.0 and 64.6 ± 5.8, p < 0.0001, mean RR interval (713 ± 74 and 943 ± 101 ms, p < 0.0001, SDNN (56.2 ± 15.7 and 87.9 ± 19.4 ms, p < 0.0001, SDANN (49.5 ± 14.7 and 76.4 ± 19.5 ms, p < 0.0001, SDNN index (24.7 ± 8.8 and 38.3 ± 13.1 ms, p < 0.0001, pNN50 (2.4 ± 1.6 and 3.2 ± 2.2 %, p < 0.0001, and RMSSD (13.5 ± 4.6 and 17.8 ± 5.4 ms, p < 0.0001 substantially improved, which sustained during both when awake and while asleep. Conclusion: Our findings suggest that treatment with ivabradine improves HRV in nonischemic patients with HF.

Knock Resistance and Fine Particle Emissions for Several Biomass-Derived Oxygenates in a Direct-Injection Spark-Ignition Engine

Energy Technology Data Exchange (ETDEWEB)

Ratcliff, Matthew A.; Burton, Jonathan; Sindler, Petr; Christensen, Earl; Fouts, Lisa; Chupka, Gina M.; McCormick, Robert L.

2016-04-01

Several high octane number oxygenates that could be derived from biomass were blended with gasoline and examined for performance properties and their impact on knock resistance and fine particle emissions in a single cylinder direct-injection spark-ignition engine. The oxygenates included ethanol, isobutanol, anisole, 4-methylanisole, 2-phenylethanol, 2,5-dimethyl furan, and 2,4-xylenol. These were blended into a summertime blendstock for oxygenate blending at levels ranging from 10 to 50 percent by volume. The base gasoline, its blends with p-xylene and p-cymene, and high-octane racing gasoline were tested as controls. Relevant gasoline properties including research octane number (RON), motor octane number, distillation curve, and vapor pressure were measured. Detailed hydrocarbon analysis was used to estimate heat of vaporization and particulate matter index (PMI). Experiments were conducted to measure knock-limited spark advance and particulate matter (PM) emissions. The results show a range of knock resistances that correlate well with RON. Molecules with relatively low boiling point and high vapor pressure had little effect on PM emissions. In contrast, the aromatic oxygenates caused significant increases in PM emissions (factors of 2 to 5) relative to the base gasoline. Thus, any effect of their oxygen atom on increasing local air-fuel ratio was outweighed by their low vapor pressure and high double-bond equivalent values. For most fuels and oxygenate blend components, PMI was a good predictor of PM emissions. However, the high boiling point, low vapor pressure oxygenates 2-phenylethanol and 2,4-xylenol produced lower PM emissions than predicted by PMI. This was likely because they did not fully evaporate and combust, and instead were swept into the lube oil.

Heart transplantation on the first day of life from an anencephalic donor.

Science.gov (United States)

Parisi, F; Squitieri, C; Carotti, A; Di Carlo, D; Gagliardi, M G

1999-05-01

Heart transplantation on the first day of life, and graft harvesting from anencephalic donors, have been very rare events in the history of transplantation. At Bambino Gesù Hospital (Rome), heart transplantation was performed on a newborn 9 h after birth, using a graft harvested from an anencephalic donor. This graft achieved a good cardiocirculatory function, but the recipient died of necrotizing enterocolitis (NEC) on post-operative day (POD) 10. Despite failure, this case and other reports support the concept that hearts from anencephalic donors can work normally, and indicate that heart transplantation on the first day of life may have a favorable outcome if postoperative maintenance of multi-organ balance and function is successful.

The evolving role of the total artificial heart in the management of end-stage congenital heart disease and adolescents.

Science.gov (United States)

Ryan, Thomas D; Jefferies, John L; Zafar, Farhan; Lorts, Angela; Morales, David L S

2015-01-01

Advances in medical therapies have yielded improvement in morbidity and a decrease in mortality for patients with congenital heart disease, both surgically palliated and uncorrected. An unintended consequence is a cohort of adolescent and adult patients with heart failure who require alternative therapies. One intriguing option is placement of a total artificial heart (TAH) either as a bridge to transplant or as a destination therapy. Of the 1091 Jarvik-7 type TAH (Symbion, CardioWest and SynCardia) placed between 1985 and 2012, only 24 have been performed in patients with congenital heart disease, and a total of 51 were placed in patients younger than 21. At our institution, the SynCardia TAH was implanted in a 19-year-old patient with cardiac allograft failure because of chronic rejection and related multisystem organ failure including need for hemodialysis. Over the next year, she was nutritionally and physically rehabilitated, as were her end organs, allowing her to come off dialysis, achieve normal renal function and eventually be successfully transplanted. Given the continued growth of adolescent and adult congenital heart disease populations with end-stage heart failure, the TAH may offer therapeutic options where previously there were few. In addition, smaller devices such as the SynCardia 50/50 will open the door for applications in smaller children. The Freedom Driver offers the chance for patients to leave the hospital with a TAH, as does the AbioCor, which is a fully implantable TAH option. In this report, we review the history of the TAH and potential applications in adolescent patients and congenital heart disease.

Spatial and temporal lineage analysis of a Pitx3-driven Cre-recombinase knock-in mouse model.

Directory of Open Access Journals (Sweden)

Marten P Smidt

Full Text Available Development and function of mesodiencephalic dopaminergic (mdDA neurons has received a lot of scientific interest since these neurons are critically involved in neurological diseases as Parkinson and psychiatric diseases as schizophrenia, depression and attention deficit hyperactivity disorder (ADHD. The understanding of the molecular processes that lead to normal development and function of mdDA neurons has provided insight in the pathology and provided critical information on new treatment paradigms. In order to be able to study specific genetic ablation in mdDA neurons a new tools was developed that drives Cre-recombinase under the control of the Pitx3 locus. The Pitx3 gene is well known for its specific expression in mdDA neurons and is present at the onset of terminal differentiation. Analysis of newly generated Pitx3-Cre knock-in mice shows that Cre expression, measured through the activation of eYfp by removal of a "Stop" signal (LoxP-Stop-LoxP-eYfp reporter mouse, is present at the onset of terminal differentiation and mimics closely the native Pitx3 expression domain. In conclusion, we present here a new Cre-driver mouse model to be used in the restricted ablation of interesting genes in mdDA neurons in order to improve our understanding of the underlying molecular programming.

Doppler ultrasound evaluation of cerebral blood flow pattern in neonates with congenital heart disease

International Nuclear Information System (INIS)

Kim, Tae Hoon; Kim, Mi Young; Kim, Yang Min; Lee, Soo Hyun; Kim, Soo Jin; Kim, Woong Han

2003-01-01

To evaluate intracerebral resistive index (RI) values in neonates with congenital heart disease and to investigate their changes after the corrective surgery of the congenital heart disease. Sixty nine neonates with congenital heart disease who underwent brain ultrasonography were included. Resistive index values were obtained at the genu portion of the anterior cerebral arteries through the anterior fontanelles. The patients were divided into 4 groups according to the presence of associated patent ductus arteriosus (PDA) and intracranial RI values. We evaluated the types of congenital heart disease that could influence RI values. Resistive index values were statistically higher in patients with PDA than in patients without PDA (p<0.05). RI values were higher in cases of large PDA with left-to-right shunt, but within the normal range in cases of small or nearly closing PDA or large PDA with bidirectional blood flow or with right-to-left shunt. For those patients without PDA, RI values were higher when patients had pulmonary atresia with multiple collateral vessels into the lung or when truncus arteriosus was present. RI values were also high in patients with hypoplastic left heart syndrome. RI values were normalized after the ligation of PDA, but patients with hypoplastic left heart syndrome showed persistently high RI values even after the Norwood's operation with Blalock-Taussig shunt. RI values are influenced by various congenital heart diseases except PDA. Therefore, the presences of the congenital heart disease and its hemodynamic changes should be taken into consideration in the evaluation of the intracranial RI values using Doppler ultrasonography.