Immunostimulant, cerebroprotective & nootropic activities of Andrographis paniculata leaves extract in normal & type 2 diabetic rats

PubMed Central

Radhika, P.; Annapurna, A.; Rao, S. Nageswara

2012-01-01

Background & objectives: A large number of plants have been recognized to be effective in the treatment of diabetes mellitus. Persistent hyperglycaemia is associated with decreased function of immune system and cerebral ischaemia mainly due to increased oxidative stress and inflammatory response. Andrographis paniculata is a medicinal plant widely used in folk medicine for various purposes. In this study the effect of chronic administration (7 days) of methanolic extract of A. paniculata leaves was studied in rats with experimentally induced diabetes, nootropic and immunostimulant activities were evaluated. The effect of acute administration of methanolic extract of A. paniculata leaves was also studied for cerebroprotective activity. Methods: Type 2 diabetes was induced in rats by streptozotocin (STZ) (65 mg/kg) + nicotinamide (150 mg/kg). Various biochemical parameters were estimated using standard methods. Results: A significant (P<0.05) increase in cognitive function was observed in both normal and type 2 diabetic rats. Nootropic activity in terms of per cent reduction in latency period was more in type 2 diabetic rats. A significant increase in blood lymphocyte count, splenic lymphocyte count and peritoneal macrophage count was observed in both normal and type 2 diabetic rats. Immunostimulant activity was observed more in type 2 diabetic rats. The per cent decrease in cerebral infarction was more in type 2 diabetic rats when compared to normal rats. The per cent increase in superoxide dismutase (SOD) levels was more in type 2 diabetic rats. Interpretation & conclusions: The antioxidant activity of the methanolic extract of A. paniculata leaves was evident by decreased tissue malondialdehyde (MDA) levels and increased SOD levels. These properties may be responsible for the observed cerebroprotective activity. The methanolic leaf extract of A. paniculata showed significant immunostimulant, cerebroprotective and nootropic activities in normal and type 2 diabetic rats. PMID:22771592

Intrathecal Infusion of Hydrogen-Rich Normal Saline Attenuates Neuropathic Pain via Inhibition of Activation of Spinal Astrocytes and Microglia in Rats

PubMed Central

Sun, Xuejun; Xiang, Zhenghua; Yang, Liqun; Huang, Shengdong; Lu, Zhijie; Sun, Yuming; Yu, Wei-Feng

2014-01-01

Background Reactive oxygen and nitrogen species are key molecules that mediate neuropathic pain. Although hydrogen is an established antioxidant, its effect on chronic pain has not been characterized. This study was to investigate the efficacy and mechanisms of hydrogen-rich normal saline induced analgesia. Methodology/Principal findings In a rat model of neuropathic pain induced by L5 spinal nerve ligation (L5 SNL), intrathecal injection of hydrogen-rich normal saline relieved L5 SNL-induced mechanical allodynia and thermal hyperalgesia. Importantly, repeated administration of hydrogen-rich normal saline did not lead to tolerance. Preemptive treatment with hydrogen-rich normal saline prevented development of neuropathic pain behavior. Immunofluorochrome analysis revealed that hydrogen-rich normal saline treatment significantly attenuated L5 SNL-induced increase of 8-hydroxyguanosine immunoreactive cells in the ipsilateral spinal dorsal horn. Western blot analysis of SDS/PAGE-fractionated tyrosine-nitrated proteins showed that L5 SNL led to increased expression of tyrosine-nitrated Mn-containing superoxide dismutase (MnSOD) in the spinal cord, and hydrogen-rich normal saline administration reversed the tyrosine-nitrated MnSOD overexpression. We also showed that the analgesic effect of hydrogen-rich normal saline was associated with decreased activation of astrocytes and microglia, attenuated expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the spinal cord. Conclusion/Significance Intrathecal injection of hydrogen-rich normal saline produced analgesic effect in neuropathic rat. Hydrogen-rich normal saline-induced analgesia in neuropathic rats is mediated by reducing the activation of spinal astrocytes and microglia, which is induced by overproduction of hydroxyl and peroxynitrite. PMID:24857932

Increased Error-Related Negativity (ERN) in Childhood Anxiety Disorders: ERP and Source Localization

ERIC Educational Resources Information Center

Ladouceur, Cecile D.; Dahl, Ronald E.; Birmaher, Boris; Axelson, David A.; Ryan, Neal D.

2006-01-01

Background: In this study we used event-related potentials (ERPs) and source localization analyses to track the time course of neural activity underlying response monitoring in children diagnosed with an anxiety disorder compared to age-matched low-risk normal controls. Methods: High-density ERPs were examined following errors on a flanker task…

Evaluation of toxicity after one-months treatment with Bauhinia forficata decoction in streptozotocin-induced diabetic rats

PubMed Central

Pepato, Maria Teresa; Baviera, Amanda Martins; Vendramini, Regina Célia; Brunetti, Iguatemy Lourenço

2004-01-01

Background Previous experiments have shown that a decoction of Bauhinia forficata leaves reduces the changes in carbohydrate and protein metabolism that occur in rats with streptozotocin-induced diabetes. In the present investigation, the serum activities of enzymes known to be reliable toxicity markers were monitored in normal and streptozotocin-diabetic rats to discover whether the use of B. forficata decoction has toxic effects on liver, muscle or pancreas tissue or on renal microcirculation. Methods An experimental group of normal and streptozotocin-diabetic rats received an aqueous decoction of fresh B. forficata leaves (150 g/L) by mouth for 33 days while a control group of normal and diabetic rats received water for the same length of time. The serum activity of the toxicity markers lactate dehydrogenase, creatine kinase, amylase, angiotensin-converting enzyme and bilirubin were assayed before receiving B. forficata decoction and on day 19 and 33 of treatment. Results The toxicity markers in normal and diabetic rats were not altered by the diabetes itself nor by treatment with decoction. Whether or not they received B. forficata decoction the normal rats showed a significant increase in serum amylase activity during the experimental period while there was a tendency for the diabetic rats, both treated and untreated with decoction, to have lower serum amylase activities than the normal rats. Conclusions Administration of an aqueous decoction of B. forficata is a potential treatment for diabetes and does not produce toxic effects measurable with the enzyme markers used in our study. PMID:15186500

Technical note: An improved approach to determining background aerosol concentrations with PILS sampling on aircraft

NASA Astrophysics Data System (ADS)

Fukami, Christine S.; Sullivan, Amy P.; Ryan Fulgham, S.; Murschell, Trey; Borch, Thomas; Smith, James N.; Farmer, Delphine K.

2016-07-01

Particle-into-Liquid Samplers (PILS) have become a standard aerosol collection technique, and are widely used in both ground and aircraft measurements in conjunction with off-line ion chromatography (IC) measurements. Accurate and precise background samples are essential to account for gas-phase components not efficiently removed and any interference in the instrument lines, collection vials or off-line analysis procedures. For aircraft sampling with PILS, backgrounds are typically taken with in-line filters to remove particles prior to sample collection once or twice per flight with more numerous backgrounds taken on the ground. Here, we use data collected during the Front Range Air Pollution and Photochemistry Éxperiment (FRAPPÉ) to demonstrate that not only are multiple background filter samples are essential to attain a representative background, but that the chemical background signals do not follow the Gaussian statistics typically assumed. Instead, the background signals for all chemical components analyzed from 137 background samples (taken from ∼78 total sampling hours over 18 flights) follow a log-normal distribution, meaning that the typical approaches of averaging background samples and/or assuming a Gaussian distribution cause an over-estimation of background samples - and thus an underestimation of sample concentrations. Our approach of deriving backgrounds from the peak of the log-normal distribution results in detection limits of 0.25, 0.32, 3.9, 0.17, 0.75 and 0.57 μg m-3 for sub-micron aerosol nitrate (NO3-), nitrite (NO2-), ammonium (NH4+), sulfate (SO42-), potassium (K+) and calcium (Ca2+), respectively. The difference in backgrounds calculated from assuming a Gaussian distribution versus a log-normal distribution were most extreme for NH4+, resulting in a background that was 1.58× that determined from fitting a log-normal distribution.

Diet, physical activity, and sedentary behaviors as risk factors for overweight in adolescence.

PubMed

Patrick, Kevin; Norman, Gregory J; Calfas, Karen J; Sallis, James F; Zabinski, Marion F; Rupp, Joan; Cella, John

2004-04-01

The proportion of overweight adolescents has increased, but the behavioral risk factors for overweight youth are not well understood. To examine how diet, physical activity, and sedentary behaviors relate to overweight status in adolescents. Baseline data from the Patient-Centered Assessment and Counseling for Exercise Plus Nutrition Project, a randomized controlled trial of adolescents to determine the effects of a clinic-based intervention on physical activity and dietary behaviors. A total of 878 adolescents aged 11 to 15 years, 42% of whom were from minority backgrounds. Centers for Disease Control and Prevention body mass index-for-age percentiles divided into 2 categories: normal weight (<85th percentile) and at risk for overweight plus overweight (AR + O) (>or=85th percentile). Overall, 45.7% of the sample was classified as AR + O with a body mass index for age at the 85th percentile or higher. More girls from minority backgrounds (54.8%) were AR + O compared with non-Hispanic white girls (42%) (chi(2)(1) = 7.6; P =.006). Bivariate analyses indicated that girls and boys in the AR + O group did fewer minutes per day of vigorous physical activity, consumed fewer total kilojoules per day, and had fewer total grams of fiber per day than those in the normal-weight group. Boys in the AR + O group also did fewer minutes per day of moderate physical activity and watched more minutes per day of television on nonschool days than normal-weight boys. Final multivariate models indicated that independent of socioeconomic status (as assessed by household education level), girls had a greater risk of being AR + O if they were Hispanic or from another minority background (odds ratio [OR] = 1.65; 95% confidence interval [CI], 1.09-2.49) and a reduced risk of being AR + O as minutes per day of vigorous physical activity increased (OR = 0.93; 95% CI, 0.89-0.97). A low level of vigorous physical activity was the only significant risk factor for boys being AR + O (OR = 0.92; 95% CI, 0.89-0.95). Analyses based on meeting behavioral guidelines supported these findings and showed that failing to meet the 60 min/d moderate to vigorous physical activity guideline was associated with overweight status for both girls and boys. In addition, boys who failed to meet sedentary behavior and dietary fiber guidelines were more likely to be overweight. Of the 7 dietary and physical activity variables examined in this cross-sectional study, insufficient vigorous physical activity was the only risk factor for higher body mass index for adolescent boys and girls. Prospective studies are needed to clarify the relative importance of dietary and physical activity behaviors on overweight in adolescence.

Pathophysiology of dysarthria in cerebral palsy.

PubMed Central

Neilson, P D; O'Dwyer, N J

1981-01-01

Electromyograms were recorded with hooked-wire electrodes from sixteen lip, tongue and jaw muscles in six normal and seven cerebral palsied adult subjects during a variety of speech and non-speech tasks. The recorded patterns of muscle activity fail to support a number of theories concerning the pathophysiology of dysarthria in cerebral palsy. There was no indication of weakness in individual articulator muscles. There was no evidence of uncontrolled sustained background activity or of abnormal tonic stretch reflex responses in lip or tongue muscles. Primitive or pathological reflexes could not be elicited by orofacial stimulation. No imbalance between positive and negative oral responses was observed. The view that random involuntary movement disrupts essentially normal voluntary control in athetosis was not supported. Each cerebral palsied subject displayed an idiosyncratic pattern of abnormal muscle activity which was reproduced across repetitions of the same phrase, indicating a consistent defect in motor programming. PMID:7334387

Differences of brain electrical activity between moderate and severe obstructive sleep apneic patients: a LORETA study.

PubMed

Toth, Marton; Kondakor, Istvan; Faludi, Bela

2016-10-01

The effects of initiation of continuous positive airway pressure (CPAP) therapy on electroencephalographic (EEG) background activity were investigated in patients exhibiting both moderate (n = 13) and severe (n = 12) obstructive sleep apnea syndromes in the testing of the potential differences of alterations of brain electrical activity caused by chronic hypoxia between these two groups. A normal control group (n = 14) was also examined. Two EEG examinations were achieved in each group: before and after first-time CPAP therapy. Low-resolution electromagnetic tomography (LORETA) was implemented towards localizing the generators of EEG activity in separate frequency bands. Prior to CPAP treatment, as a common direction of change, analysis with LORETA demonstrated increased activity in comparison with the patient and control groups. In the moderate group, significant changes were detected in the alpha2 band in the posterior cingulate cortex as well as in the beta1 band in the right posterior parietal cortex and the left supramarginal gyrus. In the severe group, significant changes were found in theta and alpha1 bands in the posterior cingulate cortex. Following CPAP treatment, these significant differences vanished in the severe group. In the moderate group, significantly decreased activity was seen in the beta3 band in the right fusiform gyrus. These findings potentially suggest a normalizing effect of CPAP therapy on EEG background activity in both groups of obstructive sleep apnea syndrome patients. Compensatory alterations of brain electrical activity in regions associated with influencing successful memory retrieval, emotional perception, default mode network, anorexia and fear network caused by chronic intermittent hypoxia could possibly be reversed with the use of CPAP therapy. © 2016 European Sleep Research Society.

Application of neuro-fuzzy methods to gamma spectroscopy

NASA Astrophysics Data System (ADS)

Grelle, Austin L.

Nuclear non-proliferation activities are an essential part of national security activities both domestic and abroad. The safety of the public in densely populated environments such as urban areas or large events can be compromised if devices using special nuclear materials are present. Therefore, the prompt and accurate detection of these materials is an important topic of research, in which the identification of normal conditions is also of importance. With gamma-ray spectroscopy, these conditions are identified as the radiation background, which though being affected by a multitude of factors is ever present. Therefore, in nuclear non-proliferation activities the accurate identification of background is important. With this in mind, a method has been developed to utilize aggregate background data to predict the background of a location through the use of an Artificial Neural Network (ANN). After being trained on background data, the ANN is presented with nearby relevant gamma-ray spectroscopy data---as identified by a Fuzzy Inference System - to create a predicted background spectra to compare to a measured spectra. If a significant deviation exists between the predicted and measured data, the method alerts the user such that a more thorough investigation can take place. Research herein focused on data from an urban setting in which the number of false positives was observed to be 28 out of a total of 987, representing 2.94% error. The method therefore currently shows a high rate of false positives given the current configuration, however there are promising steps that can be taken to further minimize this error. With this in mind, the method stands as a potentially significant tool in urban nuclear nonproliferation activities.

Comparative analysis of background EEG activity in childhood absence epilepsy during valproate treatment: a standardized, low-resolution, brain electromagnetic tomography (sLORETA) study.

PubMed

Shin, Jung-Hyun; Eom, Tae-Hoon; Kim, Young-Hoon; Chung, Seung-Yun; Lee, In-Goo; Kim, Jung-Min

2017-07-01

Valproate (VPA) is an antiepileptic drug (AED) used for initial monotherapy in treating childhood absence epilepsy (CAE). EEG might be an alternative approach to explore the effects of AEDs on the central nervous system. We performed a comparative analysis of background EEG activity during VPA treatment by using standardized, low-resolution, brain electromagnetic tomography (sLORETA) to explore the effect of VPA in patients with CAE. In 17 children with CAE, non-parametric statistical analyses using sLORETA were performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between the untreated and treated condition. Maximum differences in current density were found in the left inferior frontal gyrus for the delta frequency band (log-F-ratio = -1.390, P > 0.05), the left medial frontal gyrus for the theta frequency band (log-F-ratio = -0.940, P > 0.05), the left inferior frontal gyrus for the alpha frequency band (log-F-ratio = -0.590, P > 0.05), and the left anterior cingulate for the beta frequency band (log-F-ratio = -1.318, P > 0.05). However, none of these differences were significant (threshold log-F-ratio = ±1.888, P < 0.01; threshold log-F-ratio = ±1.722, P < 0.05). Because EEG background is accepted as normal in CAE, VPA would not be expected to significantly change abnormal thalamocortical oscillations on a normal EEG background. Therefore, our results agree with currently accepted concepts but are not consistent with findings in some previous studies.

Soleus and lateral gastrocnemius H-reflexes during standing with unstable footwear.

PubMed

Friesenbichler, Bernd; Lepers, Romuald; Maffiuletti, Nicola A

2015-05-01

Unstable footwear has been shown to increase lower extremity muscle activity, but the reflex response to perturbations induced by this intervention is unknown. Twenty healthy subjects stood in stable and unstable footwear conditions (presented randomly) while H-reflex amplitude and background muscle activity were measured in the soleus and lateral gastrocnemius (LG) muscles. Wearing unstable footwear resulted in larger H-reflexes (normalized to the maximal M-wave) for the LG (+12%; P = 0.025), but not for the soleus (+4%; P > 0.05). Background activity of both muscles was significantly higher in the unstable condition. The H-reflex facilitation observed with unstable footwear was unexpected, as challenging postural conditions usually result in reflex depression. Increased muscle activity, decreased presynaptic inhibition, and/or more forward postural position may have (over-)compensated the expected reflex depression. Differences between LG and soleus H-reflex modulation may be due to diverging motor unit recruitment thresholds. © 2015 Wiley Periodicals, Inc.

Alterations in lipids & lipid peroxidation in rats fed with flavonoid rich fraction of banana (Musa paradisiaca) from high background radiation area.

PubMed

Krishnan, Kripa; Vijayalakshmi, N R

2005-12-01

A group of villages in Kollam district of Kerala, southern part of India are exposed to a higher dose of natural radiation than global average. Yet no adverse health effects have been found in humans, animals and plants in these areas. The present study was carried out to understand whether radiation affects the quantity and quality of flavonoids in plants grown in this area of high radiation, and to assess the effect of feeding flavonoid rich fraction (FRF) of the two varieties of banana to rats on their biochemical parameters like lipids, lipid peroxides and antioxidant enzyme levels. A total of 42 albino rats were equally divided into 7 groups. Rats fed laboratory diet alone were grouped under group I (normal control). Groups II and V received flavonoid rich fraction (FRF) from the fruits of two varieties of Musa paradisiaca, Palayamkodan and Rasakadali respectively from normal background radiation area (Veli) and treated as controls. Rats of groups III and IV received FRF of Palayamkodan from high background radiation areas (HBRAs) - Neendakara and Karunagappally respectively while groups VI and VII received FRF of Rasakadali from HBRAs. At the end of the experimental period of 45 days, lipids, lipid peroxides and antioxidant enzymes from liver, heart and kidney were analyzed. FRF of Palayamkodan and Rasakadali varieties showed significant hypolipidaemic and antioxidant activities. But these activities were found to be lowered in plants grown in HBRAs, particularly in Karunagappally area. Of the two, Palayamkodan variety was more effective in reducing lipids and lipid peroxides. MDA and hydroperoxides were significantly diminished in rats given FRF of banana from Veli (control area) only. FRF from plants grown in HBRAs exerted inhibition in the activities of antioxidant enzymes in the liver of rats and this inhibitory effect was maximum in rats fed FRF from Karunagappally. Banana grown in HBRAs is of lower quality with less efficient antioxidant system. Palayamkodan was superior with its effect on hypolipidaemic and antioxidant activities. High background radiation seems to have no enhancing effect on the radioprotective action of flavonoids of banana and thereby to those consuming these fruits.

Physiologic correlates to background noise acceptance

NASA Astrophysics Data System (ADS)

Tampas, Joanna; Harkrider, Ashley; Nabelek, Anna

2004-05-01

Acceptance of background noise can be evaluated by having listeners indicate the highest background noise level (BNL) they are willing to accept while following the words of a story presented at their most comfortable listening level (MCL). The difference between the selected MCL and BNL is termed the acceptable noise level (ANL). One of the consistent findings in previous studies of ANL is large intersubject variability in acceptance of background noise. This variability is not related to age, gender, hearing sensitivity, personality, type of background noise, or speech perception in noise performance. The purpose of the current experiment was to determine if individual differences in physiological activity measured from the peripheral and central auditory systems of young female adults with normal hearing can account for the variability observed in ANL. Correlations between ANL and various physiological responses, including spontaneous, click-evoked, and distortion-product otoacoustic emissions, auditory brainstem and middle latency evoked potentials, and electroencephalography will be presented. Results may increase understanding of the regions of the auditory system that contribute to individual noise acceptance.

The buried active faults in southeastern China as revealed by the relocated background seismicity and fault plane solutions

NASA Astrophysics Data System (ADS)

Zhu, A.; Wang, P.; Liu, F.

2017-12-01

The southeastern China in the mainland corresponds to the south China block, which is characterized by moderate historical seismicity and low stain rate. Most faults are buried under thick Quaternary deposits, so it is difficult to detect and locate them using the routine geological methods. Only a few have been identified to be active in late Quaternary, which leads to relatively high potentially seismic risk to this region due to the unexpected locations of the earthquakes. We performed both hypoDD and tomoDD for the background seismicity from 2000 to 2016 to investigate the buried faults. Some buried active faults are revealed by the relocated seismicity and the velocity structure, no geologically known faults corresponding to them and no surface active evidence ever observed. The geometries of the faults are obtained by analyzing the hypocentral distribution pattern and focal mechanism. The focal mechanism solutions indicate that all the revealed faults are dominated in strike-slip mechanisms, or with some thrust components. While the previous fault investigation and detection results show that most of the Quaternary faults in southeastern China are dominated by normal movement. It suggests that there may exist two fault systems in deep and shallow tectonic regimes. The revealed faults may construct the deep one that act as the seismogenic faults, and the normal faults at shallow cannot generate the destructive earthquakes. The variation in the Curie-point depths agrees well with the structure plane of the revealed active faults, suggesting that the faults may have changed the deep structure.

EEG background activity is abnormal in the temporal and inferior parietal cortex in benign rolandic epilepsy of childhood: a LORETA study.

PubMed

Besenyei, M; Varga, E; Fekete, I; Puskás, S; Hollódy, K; Fogarasi, A; Emri, M; Opposits, G; Kis, S A; Clemens, B

2012-01-01

Benign rolandic epilepsy of childhood (BERS) is an epilepsy syndrome with presumably genetic-developmental etiology. The pathological basis of this syndrome is completely unknown. We postulated that a developmental abnormality presumably results in abnormal EEG background activity findings. 20 children with typical BERS and an age- and sex-matched group of healthy control children underwent EEG recording and analysis. 60×2 s epochs of waking EEG background activity (without epileptiform potentials and artifacts) were analyzed in the 1-25 Hz frequency range, in very narrow bands (VNB, 1 Hz bandwidth). LORETA (Low Resolution Electromagnetic Tomography) localized multiple distributed sources of EEG background activity in the Talairach space. LORETA activity (current source density) was computed for 2394 voxels and 25 VNBs. Normalized LORETA data were processed to voxel-wise comparison between the BERS and control groups. Bonferroni-corrected p<0.05 Student's t-values were accepted as statistically significant. Increased LORETA activity was found in the BERS group (as compared to the controls) in the left and right temporal lobes (fusiform gyri, posterior parts of the superior, middle and inferior temporal gyri) and in the angular gyri in the parietal lobes, in the 4-6 Hz VNBs, mainly at 5 Hz. (1) Areas of abnormal LORETA activity exactly correspond to the temporal and parietal cortical areas that are major components of the Mirsky attention model and also the perisylvian speech network. Thus the LORETA findings may correspond to impaired attention and speech in BERS patients. (2) The LORETA findings may contribute to delineating the epileptic network in BERS. The novel findings may contribute to investigating neuropsychological disturbances and organization of the epileptic network in BERS. Copyright © 2011 Elsevier B.V. All rights reserved.

Method to improve cancerous lesion detection sensitivity in a dedicated dual-head scintimammography system

DOEpatents

Kieper, Douglas Arthur [Seattle, WA; Majewski, Stanislaw [Morgantown, WV; Welch, Benjamin L [Hampton, VA

2012-07-03

An improved method for enhancing the contrast between background and lesion areas of a breast undergoing dual-head scintimammographic examination comprising: 1) acquiring a pair of digital images from a pair of small FOV or mini gamma cameras compressing the breast under examination from opposing sides; 2) inverting one of the pair of images to align or co-register with the other of the images to obtain co-registered pixel values; 3) normalizing the pair of images pixel-by-pixel by dividing pixel values from each of the two acquired images and the co-registered image by the average count per pixel in the entire breast area of the corresponding detector; and 4) multiplying the number of counts in each pixel by the value obtained in step 3 to produce a normalization enhanced two dimensional contrast map. This enhanced (increased contrast) contrast map enhances the visibility of minor local increases (uptakes) of activity over the background and therefore improves lesion detection sensitivity, especially of small lesions.

Method to improve cancerous lesion detection sensitivity in a dedicated dual-head scintimammography system

DOEpatents

Kieper, Douglas Arthur [Newport News, VA; Majewski, Stanislaw [Yorktown, VA; Welch, Benjamin L [Hampton, VA

2008-10-28

An improved method for enhancing the contrast between background and lesion areas of a breast undergoing dual-head scintimammographic examination comprising: 1) acquiring a pair of digital images from a pair of small FOV or mini gamma cameras compressing the breast under examination from opposing sides; 2) inverting one of the pair of images to align or co-register with the other of the images to obtain co-registered pixel values; 3) normalizing the pair of images pixel-by-pixel by dividing pixel values from each of the two acquired images and the co-registered image by the average count per pixel in the entire breast area of the corresponding detector; and 4) multiplying the number of counts in each pixel by the value obtained in step 3 to produce a normalization enhanced two dimensional contrast map. This enhanced (increased contrast) contrast map enhances the visibility of minor local increases (uptakes) of activity over the background and therefore improves lesion detection sensitivity, especially of small lesions.

Influence of ACTG4-7-PGP (Semax) on Morphofunctional State of Hepatocytes in Chronic Emotional and Painful Stress.

PubMed

Ivanov, A V; Bobyntsev, I I; Shepeleva, O M; Kryukov, A A; Andreeva, L A; Myasoedov, N F

2017-05-01

We studied the effect of intraperitoneal administration of peptide ACTG 4-7 -PGP to male Wistar rats in doses of 5, 50, 150, and 450 μg/kg on the morphofunctional state of hepatocytes in chronic emotional and painful stress. A dose-dependent stress-limiting effect of the peptide was observed: it normalized the protein synthesis function of the liver and serum activity of ALT. The anticytolytic effect of the peptide increased with increasing its dose against the background of the increase in the relative number of multinucleated and multinucleolated cells and deceleration of the recovery of serum protein concentration. The decrease of hepatocyte cytolysis against the background of more intense morphological signs of protein synthesis processes attests to activation of reparative processes in the liver parenchyma via enhanced constitutional synthesis of protein.

Living healthier for longer: Comparative effects of three heart-healthy behaviors on life expectancy with and without cardiovascular disease

PubMed Central

2009-01-01

Background Non-smoking, having a normal weight and increased levels of physical activity are perhaps the three key factors for preventing cardiovascular disease (CVD). However, the relative effects of these factors on healthy longevity have not been well described. We aimed to calculate and compare the effects of non-smoking, normal weight and physical activity in middle-aged populations on life expectancy with and without cardiovascular disease. Methods Using multi-state life tables and data from the Framingham Heart Study (n = 4634) we calculated the effects of three heart healthy behaviours among populations aged 50 years and over on life expectancy with and without cardiovascular disease. For the life table calculations, we used hazard ratios for 3 transitions (No CVD to CVD, no CVD to death, and CVD to death) by health behaviour category, and adjusted for age, sex, and potential confounders. Results High levels of physical activity, never smoking (men), and normal weight were each associated with 20-40% lower risks of developing CVD as compared to low physical activity, current smoking and obesity, respectively. Never smoking and high levels of physical activity reduced the risks of dying in those with and without a history of CVD, but normal weight did not. Never-smoking was associated with the largest gains in total life expectancy (4.3 years, men, 4.1 years, women) and CVD-free life expectancy (3.8 and 3.4 years, respectively). High levels of physical activity and normal weight were associated with lesser gains in total life expectancy (3.5 years, men and 3.4 years, women, and 1.3 years, men and 1.0 year women, respectively), and slightly lesser gains in CVD-free life expectancy (3.0 years, men and 3.1 years, women, and 3.1 years men and 2.9 years women, respectively). Normal weight was the only behaviour associated with a reduction in the number of years lived with CVD (1.8 years, men and 1.9 years, women). Conclusions Achieving high levels of physical activity, normal weight, and never smoking, are effective ways to prevent cardiovascular disease and to extend total life expectancy and the number of years lived free of CVD. Increasing the prevalence of normal weight could further reduce the time spent with CVD in the population. PMID:20034381

A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.

PubMed

Aidoud, Nacima; Delplanque, Bernadette; Baudry, Charlotte; Garcia, Cyrielle; Moyon, Anais; Balasse, Laure; Guillet, Benjamin; Antona, Claudine; Darmaun, Dominique; Fraser, Karl; Ndiaye, Sega; Leruyet, Pascale; Martin, Jean-Charles

2018-03-22

We evaluated the effect of adding docosahexaenoic:arachidonic acids (3:2) (DHA+ARA) to 2 representative commercial infant formulas on brain activity and brain and eye lipids in an artificially reared rat pup model. The formula lipid background was either a pure plant oil blend, or dairy fat with a plant oil blend (1:1). Results at weaning were compared to breast milk-fed pups. Brain functional activity was determined by positron emission tomography scan imaging, the brain and eye fatty acid and lipid composition by targeted and untargeted lipidomics, and DHA brain regional location by mass-spectrometry imaging. The brain functional activity was normalized to controls with DHA+ARA added to the formulas. DHA in both brain and eyes was influenced by formula intake, but more than two-thirds of tissue DHA-glycerolipids remained insensitive to the dietary challenge. However, the DHA lipidome correlated better with brain function than sole DHA content ( r = 0.70 vs. r = 0.48; P < 0.05). Brain DHA regional distribution was more affected by the formula lipid background than the provision of PUFAs. Adding DHA+ARA to formulas alters the DHA content and lipidome of nervous tissue in the neonate, making it closer to dam milk-fed controls, and normalizes brain functional activity.-Aidoud, N., Delplanque, B., Baudry, C., Garcia, C., Moyon, A., Balasse, L., Guillet, B., Antona, C., Darmaun, D., Fraser, K., Ndiaye, S., Leruyet, P., Martin, J.-C. A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.

Constitutive properties of adult mammalian cardiac muscle cells

NASA Technical Reports Server (NTRS)

Zile, M. R.; Richardson, K.; Cowles, M. K.; Buckley, J. M.; Koide, M.; Cowles, B. A.; Gharpuray, V.; Cooper, G. 4th

1998-01-01

BACKGROUND: The purpose of this study was to determine whether changes in the constitutive properties of the cardiac muscle cell play a causative role in the development of diastolic dysfunction. METHODS AND RESULTS: Cardiocytes from normal and pressure-hypertrophied cats were embedded in an agarose gel, placed on a stretching device, and subjected to a change in stress (sigma), and resultant changes in cell strain (epsilon) were measured. These measurements were used to examine the passive elastic spring, viscous damping, and myofilament activation. The passive elastic spring was assessed in protocol A by increasing the sigma on the agarose gel at a constant rate to define the cardiocyte sigma-versus-epsilon relationship. Viscous damping was assessed in protocol B from the loop area between the cardiocyte sigma-versus-epsilon relationship during an increase and then a decrease in sigma. In both protocols, myofilament activation was minimized by a reduction in [Ca2+]i. Myofilament activation effects were assessed in protocol C by defining cardiocyte sigma versus epsilon during an increase in sigma with physiological [Ca2+]i. In protocol A, the cardiocyte sigma-versus-epsilon relationship was similar in normal and hypertrophied cells. In protocol B, the loop area was greater in hypertrophied than normal cardiocytes. In protocol C, the sigma-versus-epsilon relation in hypertrophied cardiocytes was shifted to the left compared with normal cells. CONCLUSIONS: Changes in viscous damping and myofilament activation in combination may cause pressure-hypertrophied cardiocytes to resist changes in shape during diastole and contribute to diastolic dysfunction.

Categorization of hyperspectral information (HSI) based on the distribution of spectra in hyperspace

NASA Astrophysics Data System (ADS)

Resmini, Ronald G.

2003-09-01

Hyperspectral information (HSI) data are commonly categorized by a description of the dominant physical geographic background captured in the image cube. In other words, HSI categorization is commonly based on a cursory, visual assessment of whether the data are of desert, forest, urban, littoral, jungle, alpine, etc., terrains. Additionally, often the design of HSI collection experiments is based on the acquisition of data of the various backgrounds or of objects of interest within the various terrain types. These data are for assessing and quantifying algorithm performance as well as for algorithm development activities. Here, results of an investigation into the validity of the backgrounds-driven mode of characterizing the diversity of hyperspectral data are presented. HSI data are described quantitatively, in the space where most algorithms operate: n-dimensional (n-D) hyperspace, where n is the number of bands in an HSI data cube. Nineteen metrics designed to probe hyperspace are applied to 14 HYDICE HSI data cubes that represent nine different backgrounds. Each of the 14 sets (one for each HYDICE cube) of 19 metric values was analyzed for clustering. With the present set of data and metrics, there is no clear, unambiguous break-out of metrics based on the nine different geographic backgrounds. The break-outs clump seemingly unrelated data types together; e.g., littoral and urban/residential. Most metrics are normally distributed and indicate no clustering; one metric is one outlier away from normal (i.e., two clusters); and five are comprised of two distributions (i.e., two clusters). Overall, there are three different break-outs that do not correspond to conventional background categories. Implications of these preliminary results are discussed as are recommendations for future work.

Impact of physical activity on the association of overweight and obesity with cardiovascular disease: The Rotterdam Study.

PubMed

Koolhaas, Chantal M; Dhana, Klodian; Schoufour, Josje D; Ikram, M Arfan; Kavousi, Maryam; Franco, Oscar H

2017-06-01

Background Being overweight or obese is associated with an increased risk of cardiovascular disease (CVD). Physical activity might reduce the risk associated with overweight and obesity. We examined the association between overweight and obesity and CVD risk as a function of physical activity levels in a middle-aged and elderly population. Design The study was a prospective cohort study. Methods The study included 5344 participants aged 55 years or older from the population-based Rotterdam Study. Participants were classified as having high or low physical activity based on the median of the population. Normal weight (18.5-24.9 kg/m 2 ), overweight (25.0-29.9 kg/m 2 ) and obese participants (≥30 kg/m 2 ) were categorized as having high or low physical activity to form six categories. We assessed the association of the six categories with CVD risk using Cox proportional hazard models adjusted for confounders. High physical activity and normal weight was used as the reference group. Results During 15 years of follow-up (median 10.3 years, interquartile range 8.2-11.7 years), 866 (16.2%) participants experienced a CVD event. Overweight and obese participants with low physical activity had a higher CVD risk than normal weight participants with high physical activity. The HRs and 95% confidence intervals (CIs) were 1.33 (1.07-1.66) and 1.35 (1.04-1.75), respectively. Overweight and obese participants with high physical activity did not show a higher CVD risk (HRs (95%CIs) 1.03 (0.82-1.29) and 1.12 (0.83-1.52), respectively). Conclusions Our findings suggest that the beneficial impact of physical activity on CVD might outweigh the negative impact of body mass index among middle-aged and elderly people. This emphasizes the importance of physical activity for everyone across all body mass index strata, while highlighting the risk associated with inactivity even among normal weight people.

Phenotypic regional fMRI activation patterns during memory encoding in MCI and AD

PubMed Central

Browndyke, Jeffrey N.; Giovanello, Kelly; Petrella, Jeffrey; Hayden, Kathleen; Chiba-Falek, Ornit; Tucker, Karen A.; Burke, James R.; Welsh-Bohmer, Kathleen A.

2014-01-01

Background Reliable blood-oxygen-level-dependent (BOLD) fMRI phenotypic biomarkers of Alzheimer's disease (AD) or mild cognitive impairment (MCI) are likely to emerge only from a systematic, quantitative, and aggregate examination of the functional neuroimaging research literature. Methods A series of random-effects, activation likelihood estimation (ALE) meta-analyses were conducted on studies of episodic memory encoding operations in AD and MCI samples relative to normal controls. ALE analyses were based upon a thorough literature search for all task-based functional neuroimaging studies in AD and MCI published up to January 2010. Analyses covered 16 fMRI studies, which yielded 144 distinct foci for ALE meta-analysis. Results ALE results indicated several regional task-based BOLD consistencies in MCI and AD patients relative to normal controls across the aggregate BOLD functional neuroimaging research literature. Patients with AD and those at significant risk (MCI) showed statistically significant consistent activation differences during episodic memory encoding in the medial temporal lobe (MTL), specifically parahippocampal gyrus, as well superior frontal gyrus, precuneus, and cuneus, relative to normal controls. Conclusions ALE consistencies broadly support the presence of frontal compensatory activity, MTL activity alteration, and posterior midline “default mode” hyperactivation during episodic memory encoding attempts in the diseased or prospective pre-disease condition. Taken together these robust commonalities may form the foundation for a task-based fMRI phenotype of memory encoding in AD. PMID:22841497

Exploring the X-Ray Universe

NASA Astrophysics Data System (ADS)

Seward, Frederick D.; Charles, Philip A.

1995-11-01

Exploring the X-Ray Universe describes the view of the stars and galaxies that is obtained through X-ray telescopes. X-rays, which are invisible to human sight, are created in the cores of active galaxies, in cataclysmic stellar explosions, and in streams of gas expelled by the Sun and stars. The window on the heavens used by the X-ray astronomers shows the great drama of cosmic violence on the grandest scale.

The Functionality of Facial Appearance and Its Importance to a Korean Population

PubMed Central

Kim, Young Jun; Park, Jang Wan; Kim, Jeong Min; Park, Sun Hyung; Hwang, Jae Ha; Lee, Sam Yong; Shin, Jun Ho

2013-01-01

Background Many people have an interest in the correction of facial scars or deformities caused by trauma. The increasing ability to correct such flaws has been one of the reasons for the increase in the popularity of facial plastic surgery. In addition to its roles in communication, breathing, eating, olfaction and vision, the appearance of the face also plays an important role in human interactions, including during social activities. However, studies on the importance of the functional role of facial appearance. As a function of the face are scare. Therefore, in the present study, we evaluated the importance of the functions of the face in Korea. Methods We conducted an online panel survey of 300 participants (age range, 20-70 years). Each respondent was administered the demographic data form, Facial Function Assessment Scale, Rosenberg Self-Esteem Scale, and standard gamble questionnaires. Results In the evaluation on the importance of facial functions, a normal appearance was considered as important as communication, breathing, speech, and vision. Of the 300 participants, 85% stated that a normal appearance is important in social activities. Conclusions The results of this survey involving a cross-section of the Korean population indicated that a normal appearance was considered one of the principal facial functions. A normal appearance was considered more important than the functions of olfaction and expression. Moreover, a normal appearance was determined to be an important facial function for leading a normal life in Korea. PMID:24286044

Turbulent Fluid Motion 5: Fourier Analysis, the Spectral Form of the Continuum Equations, and Homogeneous Turbulence

NASA Technical Reports Server (NTRS)

Deissler, Robert G.

1996-01-01

Background material on Fourier analysis and on the spectral form of the continuum equations, both averaged and unaveraged, are given. The equations are applied to a number of cases of homogeneous turbulence with and without mean gradients. Spectral transfer of turbulent activity between scales of motion is studied in some detail. The effects of mean shear, heat transfer, normal strain, and buoyancy are included in the analyses.

The background model in the energy range from 0.1 MeV up to several MeV for low altitude and high inclination satellites.

NASA Astrophysics Data System (ADS)

Arkhangelskaja, I. V.; Arkhangelskiy, A. I.

2016-02-01

The gamma-ray background physical origin for low altitude orbits defined by: diffuse cosmic gamma-emission, atmospheric gamma-rays, gamma-emission formed in interactions of charged particles (both prompt and activation) and transient events such as electrons precipitations and solar flares. The background conditions in the energy range from 0.1 MeV up to several MeV for low altitude orbits differ due to frequency of Earth Radiation Belts - ERBs (included South Atlantic Anomaly - SAA) passes and cosmic rays rigidity. The detectors and satellite constructive elements are activated by trapped in ERBs and moving along magnetic lines charged particles. In this case we propose simplified polynomial model separately for polar and equatorial orbits parts: background count rate temporal profile approximation by 4-5 order polynomials in equatorial regions, and linear approximations, parabolas or constants in polar caps. The polynomials’ coefficients supposed to be similar for identical spectral channels for each analyzed equatorial part taken into account normalization coefficients defined due to Kp-indexes study within period corresponding to calibration coefficients being approximately constants. The described model was successfully applied for the solar flares hard X-ray and gamma-ray emission characteristic studies by AVS-F apparatus data onboard CORONAS-F satellite.

Radiation dose in the high background radiation area in Kerala, India.

PubMed

Christa, E P; Jojo, P J; Vaidyan, V K; Anilkumar, S; Eappen, K P

2012-03-01

A systematic radiological survey has been carried out in the region of high-background radiation area in Kollam district of Kerala to define the natural gamma-radiation levels. One hundred and forty seven soil samples from high-background radiation areas and five samples from normal background region were collected as per standard sampling procedures and were analysed for (238)U, (232)Th and (40)K by gamma-ray spectroscopy. External gamma dose rates at all sampling locations were also measured using a survey meter. The activities of (238)U, (232)Th and (40)K was found to vary from 17 to 3081 Bq kg(-1), 54 to 11976 Bq kg(-1) and BDL (67.4 Bq kg(-1)) to 216 Bq kg(-1), respectively, in the study area. Such heterogeneous distribution of radionuclides in the region may be attributed to the deposition phenomenon of beach sand soil in the region. Radium equivalent activities were found high in several locations. External gamma dose rates estimated from the levels of radionuclides in soil had a range from 49 to 9244 nGy h(-1). The result of gamma dose rate measured at the sampling sites using survey meter showed an excellent correlation with dose rates computed from the natural radionuclides estimated from the soil samples.

Insulin secretion enhancing activity of roselle calyx extract in normal and streptozotocin-induced diabetic rats

PubMed Central

Wisetmuen, Eamruthai; Pannangpetch, Patchareewan; Kongyingyoes, Bunkerd; Kukongviriyapan, Upa; Yutanawiboonchai, Wiboonchai; Itharat, Arunporn

2013-01-01

Background and Objective: Our recent study revealed the antihyperglycemic activity of an ethanolic extract of roselle calyxes (Hibiscus sabdariffa) in diabetic rats. The present study had, therefore, an objective to investigate the mechanism underlying this activity. Materials and Methods: Male Sprague Dawley rats were induced to be diabetes by intraperitoneal injection of 45 mg/kg streptozotocin (STZ). Normal rats as well as diabetic rats were administered with the ethanolic extract of H. sabdariffa calyxes (HS-EE) at 0.1 and 1.0 g/kg/day, respectively, for 6 weeks. Then, blood glucose and insulin levels, at basal and glucose-stimulated secretions, were measured. The pancreas was dissected to examine histologically. Results: HS-EE 1.0 g/kg/day significantly decreased the blood glucose level by 38 ± 12% in diabetic rats but not in normal rats. In normal rats, treatment with 1.0 g/kg HS-EE increased the basal insulin level significantly as compared with control normal rats (1.28 ± 0.25 and 0.55 ± 0.05 ng/ml, respectively). Interestingly, diabetic rats treated with 1.0 g/kg HS-EE also showed a significant increase in basal insulin level as compared with the control diabetic rats (0.30 ± 0.05 and 0.15 ± 0.01 ng/ml, respectively). Concerning microscopic histological examination, HS-EE 1.0 g/kg significantly increased the number of islets of Langerhans in both normal rats (1.2 ± 0.1 and 2.0 ± 0.1 islet number/10 low-power fields (LPF) for control and HS-EE treated group, respectively) and diabetic rats (1.0 ± 0.3 and 3.9 ± 0.6 islet number/10 LPF for control and HS-EE treated group, respectively). Conclusion: The antidiabetic activity of HS-EE may be partially mediated via the stimulating effect on insulin secretion. PMID:23798879

Rapid high-amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias

PubMed Central

O'Grady, Gregory; Du, Peng; Paskaranandavadivel, Nira; Angeli, Timothy R.; Lammers, Wim JEP; Asirvatham, Samuel J.; Windsor, John A.; Farrugia, Gianrico; Pullan, Andrew J.; Cheng, Leo K.

2012-01-01

Background Gastric slow waves propagate aborally as rings of excitation. Circumferential propagation does not normally occur, except at the pacemaker region. We hypothesized that: i) the unexplained high-velocity, high-amplitude activity associated with the pacemaker region is a consequence of circumferential propagation; ii) rapid, high-amplitude circumferential propagation emerges during gastric dysrhythmias; iii) the driving network conductance might switch between ICC-MP and circular ICC-IM during circumferential propagation; iv) extracellular amplitudes and velocities are correlated. Methods An experimental-theoretical study was performed. HR gastric mapping was performed in pigs during normal activation, pacing and dysrhythmia. Activation profiles, velocities and amplitudes were quantified. ICC pathways were theoretically evaluated in a bidomain model. Extracellular potentials were modelled as a function of membrane potentials. Key Results High-velocity, high-amplitude activation was only recorded in the pacemaker region when circumferential conduction occurred. Circumferential propagation accompanied dysrhythmia in 8/8 experiments, was faster than longitudinal propagation (8.9 vs 6.9 mm/s; p=0.004), and of higher amplitude (739 vs 528 μV; p=0.007). Simulations predicted that ICC-MP could be the driving network during longitudinal propagation, whereas during ectopic pacemaking, ICC-IM could outpace and activate ICC-MP in the circumferential axis. Experimental and modeling data demonstrated a linear relationship between velocities and amplitudes (p<0.001). Conclusions & Inferences The high-velocity and high-amplitude profile of the normal pacemaker region is due to localized circumferential propagation. Rapid circumferential propagation also emerges during a range of gastric dysrhythmias, elevating extracellular amplitudes and organizing transverse wavefronts. One possible explanation for these findings is bidirectional coupling between ICC-MP and circular ICC-IM networks. PMID:22709238

Modeling Seasonal Thermal Radiance Cycles for Change Detection at Volcanic / Geothermal Areas

NASA Astrophysics Data System (ADS)

Vaughan, R.; Beuttel, B. S.

2013-12-01

Remote sensing observations of thermal features associated with (and often preceding) volcanic activity have been used for decades to detect and monitor volcanism. However, anomalous thermal precursors to volcanic eruptions are usually only recognized retrospectively. One of the reasons for this is that precursor thermal activity is often too subtle in magnitude (spatially, temporally, or in absolute temperature) to be unambiguously detected in time to issue warnings or forecasts. Part of the reason for this is the trade-off between high spatial and high temporal resolution associated with satellite imaging systems. Thus, the goal of this work has been to develop some techniques for using high-temporal-resolution, coarse-spatial-resolution imagery to try to detect subtle thermal anomalies. To identify anomalies, background thermal activity must first be characterized. Every active, or potentially active, volcano has a unique thermal history that provides information about normal background thermal activity due to seasonal or diurnal variations. Understanding these normal variations allows recognition of anomalous activity that may be due to volcanic / hydrothermal processes - ultimately with a lead time that may be sufficient to issue eruption warnings or forecasts. Archived MODIS data, acquired ~daily from 2000 to 2012, were used to investigate seasonal thermal cycles at three volcanic areas with different types of thermal features: Mount St. Helens, which had a dacite dome-building eruption from 2004-2008; Mount Ruapehu, which has a 500-m diameter active summit crater lake; and Yellowstone, which is a large active geothermal system that has hundreds of hot springs and fumarole fields spread out over a very large area. The focus has been on using MODIS 1-km sensor radiance data in the MIR and TIR wavelength regions that are sensitive to thermal emission from features that range in temperature from hundreds of °C, down to tens of °C (below the boiling temperature of water). To detect such features it is best to use data acquired at night, as this maximizes the delta T between the thermal target and non-thermal background and minimizes the effects of the Sun. Decadal time-series plots of nighttime MODIS sensor radiance data over the target areas show that seasonal thermal cycles due to varying solar incidence angle can be modeled with a sine function and removed to reveal subtle changes in TIR radiance. The seasonal sine function is unique to each volcanic / geothermal area and can be modeled iteratively using a least squares fit to the cloud of radiance data. The sine function model can also be used to generate a first-order cloud cover approximation for the nighttime TIR data. This work helps establish a framework for improved thermal alarm algorithms, automated thermal detection methods, and operational monitoring techniques for active, or potentially active, volcanoes throughout the world. This type of background study is a step toward establishing a global volcanic eruption forecasting system using satellite-based remote sensing data that are sensitive to subtle precursor thermal anomalies.

Cigarette smoke–induced induction of antioxidant enzyme activities in airway leukocytes is absent in active smokers with COPD

PubMed Central

Dove, Rosamund E.; Leong-Smith, Pheneatia; Roos-Engstrand, Ester; Pourazar, Jamshid; Shah, Mittal; Behndig, Annelie F.; Mudway, Ian S.; Blomberg, Anders

2015-01-01

Background Oxidative injury to the airway has been proposed as an important underlying mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). As the extent of oxidant-mediated damage is dependent on the endogenous antioxidant defences within the airways, we examined whether COPD was associated with deficiencies in the antioxidant network within the respiratory tract lining fluids (RTLFs) and resident airway leukocytes. We hypothesised that COPD would be associated with both basal depression of antioxidant defences and impaired adaptive antioxidant responses to cigarette smoke. Methods Low molecular weight and enzymatic antioxidants together with metal-handling proteins were quantified in bronchoalveolar lavage fluid and airway leukocytes, derived from current (n=9) and ex-smoking COPD patients (n=15), as well as from smokers with normal lung function (n=16) and healthy never smokers (n=13). Results Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers. In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers. Conclusions We found no evidence of impaired basal antioxidant defences, within either the RTLFs or airway leukocytes in stable ex-smoking COPD patients compared with healthy never smoking controls. Current cigarette smoking induced an up-regulation of low molecular weight antioxidants in the RTLFs of both control subjects with normal lung function and patients with COPD. Importantly, the present data demonstrated a cigarette smoke–induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression. PMID:26557249

Differential functional magnetic resonance imaging response to food pictures in successful weight-loss maintainers relative to normal-weight and obese controls1234

PubMed Central

Haley, Andreana P; Sweet, Lawrence H; Phelan, Suzanne; Raynor, Hollie A; Del Parigi, Angelo; Cohen, Ron; Wing, Rena R

2009-01-01

Background: Prior research indicates that successful weight-loss maintainers (SWLs) work harder than people of normal weight to maintain their weight loss, including greater dietary restriction of fat and higher physical activity levels. However, little work to date has examined how SWLs differ biologically from normal-weight (NW) and obese controls. Objective: The objective was to compare the brain responses of SWLs to food pictures with those of NW and obese controls. Design: Blood oxygen level–dependent responses to high- and low-energy food pictures were measured in 18 NW controls, 16 obese controls, and 17 SWLs. Results: Group differences were identified in 4 regions, which indicated significant change in activation in response to the food pictures. SWLs showed greater activation in the left superior frontal region and right middle temporal region than did NW and obese controls—a pattern of results confirmed in exploratory voxel-wise analyses. Obese controls also showed greater activation in a bilateral precentral region. Conclusions: These results suggest that SWLs show greater activation in frontal regions and primary and secondary visual cortices—a pattern consistent with greater inhibitory control in response to food cues and greater visual attention to the food cues. A greater engagement of inhibitory control regions in response to food cues as well as a greater monitoring of foods may promote control of food intake and successful weight-loss maintenance. PMID:19675107

Platelet ERK5 is a Redox Switch and Triggers Maladaptive Platelet Responses and Myocardial Infarct Expansion

PubMed Central

Cameron, Scott J.; Ture, Sara K.; Mickelsen, Deanne; Chakrabarti, Enakshi; Modjeski, Kristina L.; McNitt, Scott; Seaberry, Micheal; Field, David J.; Le, Nhat-Tu; Abe, Jun-ichi; Morrell, Craig N.

2015-01-01

Background Platelets have a pathophysiologic role in the ischemic microvascular environment of acute coronary syndromes (ACS). Compared to platelet activation in normal healthy conditions, less attention is given to mechanisms of platelet activation in diseased states. Platelet function and mechanisms of activation in ischemic and reactive oxygen species (ROS) rich environments may not be the same as in normal healthy conditions. Extracellular Regulated Protein Kinase 5 (ERK5) is a Mitogen Activated Protein Kinase (MAPK) family member activated in hypoxic, ROS rich environments, and in response to receptor signaling mechanisms. Prior studies suggest a protective effect of ERK5 in endothelial and myocardial cells following ischemia. We present evidence that platelets express ERK5 and platelet ERK5 has an adverse effect on platelet activation via selective receptor-dependent and receptor-independent ROS mediated mechanisms in ischemic myocardium. Methods and Results Using isolated human platelets and a mouse model of myocardial infarction (MI), we found that platelet ERK5 is activated post-MI and platelet specific ERK5−/− mice have less platelet activation, reduced MI size, and improved post-MI heart function. Furthermore, the expression of downstream ERK5 regulated proteins is reduced in ERK5−/− platelets post-MI. Conclusions ERK5 functions as a platelet activator in ischemic conditions and platelet ERK5 maintains the expression of some platelet proteins following MI, leading to infarct expansion. This demonstrates that platelet function in normal healthy conditions is different from platelet function in chronic ischemic and inflammatory conditions. Platelet ERK5 may be a target for acute therapeutic intervention in the thrombotic and inflammatory post-MI environment. PMID:25934838

Open field locomotor activity and anxiety-related behaviors in mucopolysaccharidosis type IIIA mice.

PubMed

Lau, Adeline A; Crawley, Allison C; Hopwood, John J; Hemsley, Kim M

2008-08-05

Mucopolysaccharidosis (MPS) IIIA, or Sanfilippo syndrome, is a lysosomal storage disorder characterized by severe and progressive neuropathology. Following an asymptomatic period, patients may present with sleep disturbances, cognitive decline, aggressive tendencies and hyperactivity. A naturally-occurring mouse model of MPS IIIA also exhibits many of these behavioral features and has been recently back-crossed onto a C57BL/6 genetic background. To more thoroughly characterize the behavioral phenotype of congenic MPS IIIA mice, we assessed exploratory activity and unconditioned anxiety-related behavior in the elevated plus maze (EPM) and open field locomotor activity. Although MPS IIIA male mice were less active in the EPM at 18 and 20 weeks of age, they were more likely to explore the open arms than their normal counter-parts suggesting reduced anxiety. Repeated EPM testing reduced exploration of the open arms in MPS IIIA mice. In the open field test, significant reductions in activity were evident in naïve-tested male MPS IIIA mice from 10 weeks of age. Female normal and MPS IIIA mice displayed similar exploratory activity in the open field test. These differences in anxiety and locomotor activity will allow us to evaluate the efficacy of therapeutic regimes for MPS IIIA as a forerunner to developing safe and effective therapies for Sanfilippo patients.

Adaptive Value Normalization in the Prefrontal Cortex Is Reduced by Memory Load.

PubMed

Holper, L; Van Brussel, L D; Schmidt, L; Schulthess, S; Burke, C J; Louie, K; Seifritz, E; Tobler, P N

2017-01-01

Adaptation facilitates neural representation of a wide range of diverse inputs, including reward values. Adaptive value coding typically relies on contextual information either obtained from the environment or retrieved from and maintained in memory. However, it is unknown whether having to retrieve and maintain context information modulates the brain's capacity for value adaptation. To address this issue, we measured hemodynamic responses of the prefrontal cortex (PFC) in two studies on risky decision-making. In each trial, healthy human subjects chose between a risky and a safe alternative; half of the participants had to remember the risky alternatives, whereas for the other half they were presented visually. The value of safe alternatives varied across trials. PFC responses adapted to contextual risk information, with steeper coding of safe alternative value in lower-risk contexts. Importantly, this adaptation depended on working memory load, such that response functions relating PFC activity to safe values were steeper with presented versus remembered risk. An independent second study replicated the findings of the first study and showed that similar slope reductions also arose when memory maintenance demands were increased with a secondary working memory task. Formal model comparison showed that a divisive normalization model fitted effects of both risk context and working memory demands on PFC activity better than alternative models of value adaptation, and revealed that reduced suppression of background activity was the critical parameter impairing normalization with increased memory maintenance demand. Our findings suggest that mnemonic processes can constrain normalization of neural value representations.

Accuracy of cochlear implant recipients in speech reception in the presence of background music.

PubMed

Gfeller, Kate; Turner, Christopher; Oleson, Jacob; Kliethermes, Stephanie; Driscoll, Virginia

2012-12-01

This study examined speech recognition abilities of cochlear implant (CI) recipients in the spectrally complex listening condition of 3 contrasting types of background music, and compared performance based upon listener groups: CI recipients using conventional long-electrode devices, Hybrid CI recipients (acoustic plus electric stimulation), and normal-hearing adults. We tested 154 long-electrode CI recipients using varied devices and strategies, 21 Hybrid CI recipients, and 49 normal-hearing adults on closed-set recognition of spondees presented in 3 contrasting forms of background music (piano solo, large symphony orchestra, vocal solo with small combo accompaniment) in an adaptive test. Signal-to-noise ratio thresholds for speech in music were examined in relation to measures of speech recognition in background noise and multitalker babble, pitch perception, and music experience. The signal-to-noise ratio thresholds for speech in music varied as a function of category of background music, group membership (long-electrode, Hybrid, normal-hearing), and age. The thresholds for speech in background music were significantly correlated with measures of pitch perception and thresholds for speech in background noise; auditory status was an important predictor. Evidence suggests that speech reception thresholds in background music change as a function of listener age (with more advanced age being detrimental), structural characteristics of different types of music, and hearing status (residual hearing). These findings have implications for everyday listening conditions such as communicating in social or commercial situations in which there is background music.

Effects of the Healthy Start randomized intervention trial on physical activity among normal weight preschool children predisposed to overweight and obesity

PubMed Central

Larsen, Sofus Christian; Rohde, Jeanett Friis; Stougaard, Maria; Olsen, Nanna Julie; Heitmann, Berit Lilienthal

2017-01-01

Background There is limited evidence to support the effectiveness of primary interventions aiming to prevent excess weight gain among young children. Evaluating behavioral changes, such as physical activity (PA), may add to future development of efficient interventions. The objective was to evaluate the effect on PA outcomes of the 15 month Healthy Start intervention that focused on changing diet, PA, sleep and stress management among normal weight but obesity-prone preschool children. Children were defined as obesity-prone if they had a birth weight > 4,000 g, mothers with a pre-pregnancy body mass index of > 28 kg/m2, or mothers with ≤ 10 years of schooling. Method From a baseline study population of 635 normal weight 2–6 year old preschool children from the greater Copenhagen area, parents of 307 children had given information on PA at both the baseline and follow-up examinations. PA was obtained from a 7 days recording in the Children’s Physical Activity Questionnaire. Time used for sport activities were combined with outdoor playing time to achieve a proxy of total PA level of moderate to vigorous intensity. Results Linear regression analyses revealed that at follow-up the intervention group spent more time on sports and outdoor activities combined per week than the control group (ITT analyses: intervention: 400 min/week; 95% confidence interval (CI): 341, 459 versus control: 321 min/week; 95% CI: 277, 366; p = 0.02), although no significant intervention effects were seen for each of the subcategories, e.g. sports participation, outdoor activities, screen time, or commuting frequency. Conclusion Our results suggest that the overall time spent on sports and outdoor activities combined was increased at follow-up among normal weight obesity-prone children, as a result of the Healthy Start intervention. Trial registration ClinicalTrials.gov NCT01583335 PMID:28991907

Resting-state activity in development and maintenance of normal brain function.

PubMed

Pizoli, Carolyn E; Shah, Manish N; Snyder, Abraham Z; Shimony, Joshua S; Limbrick, David D; Raichle, Marcus E; Schlaggar, Bradley L; Smyth, Matthew D

2011-07-12

One of the most intriguing recent discoveries concerning brain function is that intrinsic neuronal activity manifests as spontaneous fluctuations of the blood oxygen level-dependent (BOLD) functional MRI signal. These BOLD fluctuations exhibit temporal synchrony within widely distributed brain regions known as resting-state networks. Resting-state networks are present in the waking state, during sleep, and under general anesthesia, suggesting that spontaneous neuronal activity plays a fundamental role in brain function. Despite its ubiquitous presence, the physiological role of correlated, spontaneous neuronal activity remains poorly understood. One hypothesis is that this activity is critical for the development of synaptic connections and maintenance of synaptic homeostasis. We had a unique opportunity to test this hypothesis in a 5-y-old boy with severe epileptic encephalopathy. The child developed marked neurologic dysfunction in association with a seizure disorder, resulting in a 1-y period of behavioral regression and progressive loss of developmental milestones. His EEG showed a markedly abnormal pattern of high-amplitude, disorganized slow activity with frequent generalized and multifocal epileptiform discharges. Resting-state functional connectivity MRI showed reduced BOLD fluctuations and a pervasive lack of normal connectivity. The child underwent successful corpus callosotomy surgery for treatment of drop seizures. Postoperatively, the patient's behavior returned to baseline, and he resumed development of new skills. The waking EEG revealed a normal background, and functional connectivity MRI demonstrated restoration of functional connectivity architecture. These results provide evidence that intrinsic, coherent neuronal signaling may be essential to the development and maintenance of the brain's functional organization.

Enhanced Somatosensory Feedback Reduces Prefrontal Cortical Activity During Walking in Older Adults

PubMed Central

Christou, Evangelos A.; Ring, Sarah A.; Williamson, John B.; Doty, Leilani

2014-01-01

Background. The coordination of steady state walking is relatively automatic in healthy humans, such that active attention to the details of task execution and performance (controlled processing) is low. Somatosensation is a crucial input to the spinal and brainstem circuits that facilitate this automaticity. Impaired somatosensation in older adults may reduce automaticity and increase controlled processing, thereby contributing to deficits in walking function. The primary objective of this study was to determine if enhancing somatosensory feedback can reduce controlled processing during walking, as assessed by prefrontal cortical activation. Methods. Fourteen older adults (age 77.1±5.56 years) with mild mobility deficits and mild somatosensory deficits participated in this study. Functional near-infrared spectroscopy was used to quantify metabolic activity (tissue oxygenation index, TOI) in the prefrontal cortex. Prefrontal activity and gait spatiotemporal data were measured during treadmill walking and overground walking while participants wore normal shoes and under two conditions of enhanced somatosensation: wearing textured insoles and no shoes. Results. Relative to walking with normal shoes, textured insoles yielded a bilateral reduction of prefrontal cortical activity for treadmill walking (ΔTOI = −0.85 and −1.19 for left and right hemispheres, respectively) and for overground walking (ΔTOI = −0.51 and −0.66 for left and right hemispheres, respectively). Relative to walking with normal shoes, no shoes yielded lower prefrontal cortical activity for treadmill walking (ΔTOI = −0.69 and −1.13 for left and right hemispheres, respectively), but not overground walking. Conclusions. Enhanced somatosensation reduces prefrontal activity during walking in older adults. This suggests a less intensive utilization of controlled processing during walking. PMID:25112494

Exercise training does not increase muscle FNDC5 protein or mRNA expression in pigs

PubMed Central

Fain, John N.; Company, Joseph M.; Booth, Frank W.; Laughlin, M. Harold; Padilla, Jaume; Jenkins, Nathan T.; Bahouth, Suleiman W.; Sacks, Harold S.

2013-01-01

Background Exercise training elevates circulating irisin and induces the expression of the FNDC5 gene in skeletal muscles of mice. Our objective was to determine whether exercise training also increases FNDC5 protein or mRNA expression in the skeletal muscles of pigs as well as plasma irisin. Methods Castrated male pigs of the Rapacz familial hypercholesterolemic (FHM) strain and normal (Yucatan miniature) pigs were sacrificed after 16–20 weeks of exercise training. Samples of cardiac muscle, deltoid and triceps brachii muscle, subcutaneous and epicardial fat were obtained and FNDC5 mRNA, along with that of 6 other genes, was measured in all tissues of FHM pigs by reverse transcription polymerase chain reaction. FNDC protein in deltoid and triceps brachii was determined by Western blotting in both FHM and normal pigs. Citrate synthase activity was measured in the muscle samples of all pigs as an index of exercise training. Irisin was measured by an ELISA assay. Results There was no statistically significant effect of exercise training on FNDC5 gene expression in epicardial or subcutaneous fat, deltoid muscle, triceps brachii muscle or heart muscle. Exercise-training elevated circulating levels of irisin in the FHM pigs and citrate synthase activity in deltoid and triceps brachii muscle. A similar increase in citrate synthase activity was seen in muscle extracts of exercise-trained normal pigs but there was no alteration in circulating irisin. Conclusion Exercise training in pigs does not increase FNDC5 mRNA or protein in the deltoid or triceps brachii of FHM or normal pigs while increasing circulating irisin only in the FHM pigs. These data indicate that the response to exercise training in normal pigs is not comparable to that seen in mice. PMID:23831442

The metabolism of primaquine to its active metabolite is dependent on CYP 2D6.

PubMed

Pybus, Brandon S; Marcsisin, Sean R; Jin, Xiannu; Deye, Gregory; Sousa, Jason C; Li, Qigui; Caridha, Diana; Zeng, Qiang; Reichard, Gregory A; Ockenhouse, Christian; Bennett, Jason; Walker, Larry A; Ohrt, Colin; Melendez, Victor

2013-06-20

The efficacy of the 8-aminoquinoline (8AQ) drug primaquine (PQ) has been historically linked to CYP-mediated metabolism. Although to date no clear evidence exists in the literature that unambiguously assigns the metabolic pathway or specific metabolites necessary for activity, recent literature suggests a role for CYP 2D6 in the generation of redox active metabolites. In the present study, the specific CYP 2D6 inhibitor paroxetine was used to assess its effects on the production of specific phenolic metabolites thought to be involved in PQ efficacy. Further, PQ causal prophylactic (developing liver stage) efficacy against Plasmodium berghei in CYP 2D knockout mice was assessed in comparison with a normal C57 background and with humanized CYP 2D6 mice to determine the direct effects of CYP 2D6 metabolism on PQ activity. PQ exhibited no activity at 20 or 40 mg/kg in CYP 2D knockout mice, compared to 5/5 cures in normal mice at 20 mg/kg. The activity against developing liver stages was partially restored in humanized CYP 2D6 mice. These results unambiguously demonstrate that metabolism of PQ by CYP 2D6 is essential for anti-malarial causal prophylaxis efficacy.

Associations between a neurophysiological marker of central cholinergic activity and cognitive functions in young and older adults

PubMed Central

2012-01-01

Background The deterioration of the central cholinergic system in aging is hypothesized to underlie declines in several cognitive domains, including memory and executive functions. However, there is surprisingly little direct evidence regarding acetylcholine’s specific role(s) in normal human cognitive aging. Methods We used short-latency afferent inhibition (SAI) with transcranial magnetic stimulation (TMS) as a putative marker of cholinergic activity in vivo in young (n = 24) and older adults (n = 31). Results We found a significant age difference in SAI, concordant with other evidence of cholinergic decline in normal aging. We also found clear age differences on several of the memory and one of the executive function measures. Individual differences in SAI levels predicted memory but not executive functions. Conclusion Individual differences in SAI levels were better predictors of memory than executive functions. We discuss cases in which the relations between SAI and cognition might be even stronger, and refer to other age-related biological changes that may interact with cholinergic activity in cognitive aging. PMID:22537877

Occurrence and distribution of contaminants in bottom sediment and water of the Barron River Canal, Big Cypress National Preserve, Florida

USGS Publications Warehouse

Miller, Ronald L.; McPherson, Benjamin F.

2001-01-01

Trace elements and organic contaminants in bottom-sediment samples collected from 10 sites on the Barron River Canal and from one site on the Turner River in October 1998 had patterns of distribution that indicated different sources. At some sites on the Barron River Canal, lead, copper, and zinc, normalized to aluminum, exceeded limits normally considered as background and may be enriched by human activities. Polynuclear aromatic hydrocarbons and p-cresol, normalized against organic carbon, had patterns of distribution that indicated local sources of input from a road or vehicular traffic or from an old creosote wood treatment facility. Phthalate esters and the traces elements arsenic, cadmium, and zinc were more widely distributed with the highest normalized concentrations occurring at the Turner River background site, probably due to the high percentage of fine sediment (74% less than 63 micrometers) and high organic carbon concentration (42%) at that site and the binding effect of organic carbon on trace elements and trace organic compounds. Low concentrations of pesticides or pesticide degradation products were detected in bottom sediment (DDD and DDE, each less than 3.5 µg/kg) and water (9 pesticides, each less than 0.06 µ/L), primarily in the northern reach of the Barron River Canal where agriculture is a likely source. Although a few contaminants approached criteria that would indicate adverse effects on aquatic life, none exceeded the criteria, but the potential synergistic effects of mixtures of contaminants found at most sites are not included in the criteria.

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase

PubMed Central

Wirth, Eva K.; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-01-01

Background The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). Methods We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated. PMID:26601078

The Impact of Listening Condition on Background Noise Acceptance for Young Adults with Normal Hearing

ERIC Educational Resources Information Center

Gordon-Hickey, Susan; Moore, Robert E.; Estis, Julie M.

2012-01-01

Purpose: To evaluate the effect of different speech conditions on background noise acceptance. A total of 23 stimulus pairings, differing in primary talker gender (female, male, conventional), number of background talkers (1, 4, 12), and gender composition of the background noise (female, male, mixed) were used to evaluate background noise…

Sonographic Features of Nodular Hashimoto Thyroiditis.

PubMed

Oppenheimer, Daniel Corey; Giampoli, Ellen; Montoya, Simone; Patel, Swapnil; Dogra, Vikram

2016-09-01

The aim of the study was to analyze the sonographic features of nodular Hashimoto thyroiditis (HT) in patients with diffuse background thyroiditis and normal background thyroid parenchyma. Eighty-six patients who had fine-needle aspiration biopsy of 100 thyroid nodules confirmed to be HT and a thyroid ultrasound within 1 year of the biopsy were included in the study. Retrospective analysis of several sonographic features of each nodule was then performed. The mean age of patients with nodular HT was 53 years, 84% of which were female. Nodular HT occurred in a background of diffuse thyroiditis in 85% and in a homogeneous normal background in 15%. Ninety-three percent of nodules were completely solid and 7% of nodules were cystic and solid. Although the sonographic appearance of nodular HT was variable, the most common appearance was a solid (93/100) and hypoechoic nodule (44/100) with a thin hypoechoic halo (42/100) without calcifications (96/100). On color Doppler, 17% of nodules showed peripheral hypervascularity, 14% of nodules were diffusely hypervascular, 34% were iso vascular, 32% were hypovascular, and 3% were avascular. The sonographic appearance of nodular HT was not significantly different in patients with diffuse background thyroiditis compared with those without background thyroiditis. The sonographic appearance of nodular HT is variable, but the most common appearance is a solid sharply circumscribed hypoechoic nodule with thin hypoechoic halo without calcification. There was no significant difference in the appearance of nodular HT in patients with diffuse background thyroiditis compared with patients with normal background thyroid parenchyma.

Development and Application of Plasma Actuators for Active Control of High-Speed and High Reynolds Number Flows

NASA Technical Reports Server (NTRS)

Sammy, Mo

2010-01-01

Active flow control is often used to manipulate flow instabilities to achieve a desired goal (e.g. prevent separation, enhance mixing, reduce noise, etc.). Instability frequencies normally scale with flow velocity scale and inversely with flow length scale (U/l). In a laboratory setting for such flow experiments, U is high, but l is low, resulting in high instability frequency. In addition, high momentum and high background noise & turbulence in the flow necessitate high amplitude actuation. Developing a high amplitude and high frequency actuator is a major challenge. Ironically, these requirements ease up in application (but other issues arise).

Perceptions & Attitudes of Male Homosexuals from Differing Socio-Cultural & Audiological Backgrounds.

ERIC Educational Resources Information Center

Swartz, Daniel B.

This study examined four male homosexual, sociocultural groups: normal-hearing homosexuals with normal-hearing parents, deaf homosexuals with normal-hearing parents, deaf homosexuals with hearing-impaired parents, and hard-of-hearing homosexuals with normal-hearing parents. Differences with regard to self-perception, identity, and attitudes were…

Statistical Study on Variations of the Ionospheric Ion Density Observed by DEMETER and Related to Seismic Activities

NASA Astrophysics Data System (ADS)

Yan, Rui; Parrot, Michel; Pinçon, Jean-Louis

2017-12-01

In this paper, we present the result of a statistical study performed on the ionospheric ion density variations above areas of seismic activity. The ion density was observed by the low altitude satellite DEMETER between 2004 and 2010. In the statistical analysis a superposed epoch method is used where the observed ionospheric ion density close to the epicenters both in space and in time is compared to background values recorded at the same location and in the same conditions. Data associated with aftershocks have been carefully removed from the database to prevent spurious effects on the statistics. It is shown that, during nighttime, anomalous ionospheric perturbations related to earthquakes with magnitudes larger than 5 are evidenced. At the time of these perturbations the background ion fluctuation departs from a normal distribution. They occur up to 200 km from the epicenters and mainly 5 days before the earthquakes. As expected, an ion density perturbation occurring just after the earthquakes and close to the epicenters is also evidenced.

Radioprotective effects of delphinidin on normal human lung cells against proton beam exposure

PubMed Central

Kim, Hyun Mi; Kim, Suk Hee

2018-01-01

BACKGROUND/OBJECTIVES Exposure of the normal lung tissue around the cancerous tumor during radiotherapy causes serious side effects such as pneumonitis and pulmonary fibrosis. Radioprotectors used during cancer radiotherapy could protect the patient from side effects induced by radiation injury of the normal tissue. Delphinidin has strong antioxidant properties, and it works as the driving force of a radioprotective effect by scavenging radiation-induced reactive oxygen species (ROS). However, no studies have been conducted on the radioprotective effect of delphinidin against high linear energy transfer radiation. Therefore, this study was undertaken to evaluate the radioprotective effects of delphinidin on human lung cells against a proton beam. MATERIALS/METHODS Normal human lung cells (HEL 299 cells) were used for in vitro experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay assessed the cytotoxicity of delphinidin and cell viability. The expression of radiation induced cellular ROS was measured by the 2′-7′-dicholordihydrofluorescein diacetate assay. Superoxide dismutase activity assay and catalase activity assay were used for evaluating the activity of corresponding enzymes. In addition, radioprotective effects on DNA damage-induced cellular apoptosis were evaluated by Western blot assay. RESULTS Experimental analysis, including cell survival assay, MTT assay, and Western blot assay, revealed the radioprotective effects of delphinidin. These include restoring the activities of antioxidant enzymes of damaged cells, increase in the levels of pro-survival protein, and decrease of pro-apoptosis proteins. The results from different experiments were compatible with each to provide a substantial conclusion. CONCLUSION Low concentration (2.5 µM/mL) of delphinidin administration prior to radiation exposure was radioprotective against a low dose of proton beam exposure. Hence, delphinidin is a promising shielding agent against radiation, protecting the normal tissues around a cancerous tumor, which are unintentionally exposed to low doses of radiation during proton therapy. PMID:29399295

Self-reported Knee Function Can Identify Athletes Who Fail Return to Activity Criteria up to 1 Year after Anterior Cruciate Ligament Reconstruction. A Delaware-Oslo ACL Cohort Study

PubMed Central

Logerstedt, David; Stasi, Stephanie Di; Grindem, Hege; Lynch, Andrew; Eitzen, Ingrid; Engebretsen, Lars; Risberg, May Arna; Axe, Michael J; Snyder-Mackler, Lynn

2014-01-01

STUDY DESIGN Cohort study, cross-sectional. OBJECTIVES To determine if self-reported knee function assessed with the International Knee Documentation Committee 2000 Subjective Knee Form (IKDC2000) could discriminate between successful and non-successful performance on return to activity criteria (RTAC) tests after anterior cruciate ligament (ACL) reconstruction. BACKGROUND Rehabilitation specialists are challenged in selecting appropriate performance-based and patient-reported tests that can detect side-to-side asymmetries, assess global knee function, and determine a participant's readiness to return to activity after ACL reconstruction. A simple tool or questionnaire that could identify athletes with neuromuscular impairments or activity limitations could provide rehabilitation specialists crucial data pertinent to their current knee function and their readiness to return to higher level activities. METHODS One hundred fifty-eight Level I/II athletes 6 months after ACL reconstruction and 141 athletes 12 months after ACL reconstruction completed a functional test battery to determine readiness to return to activity and the IKDC2000 to determine self-reported knee function. For each athlete, status on return to activity tests criteria was dichotomized as “Passed” or ”Failed” and status on the IKDC2000 scores was dichotomized as being “within” or “below age- and sex-matched normal ranges”. Comparisons were made between status on RTAC and IKDC2000 using Chi-square tests. Accuracy statistics were also calculated. RESULTS Six months after ACL reconstruction, 112 athletes (70.9%) failed RTAC and 76 (48.1%) were classified as having self-reported knee function below normal ranges. Among the 76 participants with IKDC2000 scores below normal ranges, 69 (90.8%) failed RTAC test battery (P<.001). However, among the 82 participants whose IKDC2000 scores were within normal limits at 6 months, only 39 (47.6%) passed RTAC test battery (P=.74). Twelve months after ACL reconstruction, 67 athletes (47.5%) failed RTAC and 31 (78.0%) had knee function below normal ranges. Among the 31 participants with IKDC2000 scores below normal ranges, 25 (80.6%) failed RTAC test battery (P<.001). However, among the 110 participants whose IKDC2000 scores were within normal limits at 12 months, only 68 (61.8%) passed RTAC test battery (P=.017). CONCLUSION The IKDC2000 may be a clinically relevant tool to determine the timeliness or necessity of RTAC testing. For scores obtained 6 and 12 months after ACL reconstruction, low IKDC2000 scores were reasonably indicative of failure on RTAC test battery, whereas normal IKDC2000 scores were not predictive of passing scores on the RTAC test battery. PMID:25347228

A method of computationally enhanced detection of chromatogram regions with apparent high relative agonist activity.

PubMed

Price, J A

1998-08-01

An occasional but difficult problem arises in drug discovery during a chromatographic analysis in which high background activity is associated with the presence of most eluting molecular species. This makes the isolation of material of high relative activity difficult. A computational method is shown that clarifies the identification of regions of the chromatogram of interest. The data for bioactivity and absorbance are normalized to percent of maximal response, filtered to raise very small or zero values to a minimal level, and the activity/absorbance ratio is plotted per fraction. The fractions with relatively high activity become evident. This technique is a helpful adjunct to existing graphical methods and provides an objective relationship between the data sets. It is simple to implement with Visual Basic and spreadsheet data, making it widely accessible.

Physical Activity and Heart Rate Variability in Older Adults: The Cardiovascular Health Study

PubMed Central

Soares-Miranda, Luisa; Sattelmair, Jacob; Chaves, Paulo; Duncan, Glen; Siscovick, David S; Stein, Phyllis K; Mozaffarian, Dariush

2014-01-01

Background Cardiac mortality and electrophysiologic dysfunction both increase with age. Heart rate variability (HRV) provides indices of autonomic function and electrophysiology that are associated with cardiac risk. How habitual physical activity (PA) among older adults prospectively relates to HRV, including nonlinear indices of erratic sinus patterns, is not established. We hypothesized that increasing levels of both total leisure-time activity and walking would be prospectively associated with more favorable time-domain, frequency-domain, and nonlinear HRV measures in older adults. Methods and Results We evaluated serial longitudinal measures of both PA and 24-hour Holter HRV over 5 years among 985 older US adults in the community-based Cardiovascular Health Study. After multivariable adjustment, greater total leisure-time activity, walking distance, and walking pace were each prospectively associated with specific, more favorable HRV indices, including higher 24-hour standard-deviation-of-all-normal-to-normal-intervals (SDNN, p-trend=0.009, 0.02, 0.06, respectively) and ultra-low-frequency-power (p-trend=0.02, 0.008, 0.16, respectively). Greater walking pace was also associated with higher short-term-fractal-scaling-exponent (p-trend=0.003) and lower Poincare ratio (p-trend=0.02), markers of less erratic sinus patterns. Conclusions Greater total leisure-time activity, as well as walking alone, were prospectively associated with more favorable and specific indices of autonomic function in older adults, including several suggestive of more normal circadian fluctuations and less erratic sinoatrial firing. Our results suggest potential mechanisms that might contribute to lower cardiovascular mortality with habitual PA later in life. PMID:24799513

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

PubMed Central

Chang, Xue-ying; Cui, Lei; Wang, Xing-zhi; Zhang, Lei; Zhu, Dan

2017-01-01

Background This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Results Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P < 0.05) and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Conclusions Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway. PMID:28691026

Temporary Dietary Iron Restriction Affects the Process of Thrombus Resolution in a Rat Model of Deep Vein Thrombosis

PubMed Central

Oboshi, Makiko; Naito, Yoshiro; Sawada, Hisashi; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Nishimura, Koichi; Fujii, Kenichi; Mano, Toshiaki; Ishihara, Masaharu; Masuyama, Tohru

2015-01-01

Background Deep vein thrombosis (DVT) is a major cause of pulmonary thromboembolism and sudden death. Thus, it is important to consider the pathophysiology of DVT. Recently, iron has been reported to be associated with thrombotic diseases. Hence, in this study, we investigate the effects of dietary iron restriction on the process of thrombus resolution in a rat model of DVT. Methods We induced DVT in 8-week-old male Sprague-Dawley rats by performing ligations of their inferior venae cavae. The rats were then given either a normal diet (DVT group) or an iron-restricted diet (DVT+IR group). Thrombosed inferior venae cavae were harvested at 5 days after ligation. Results The iron-restricted diet reduced venous thrombus size compared to the normal diet. Intrathrombotic collagen content was diminished in the DVT+IR group compared to the DVT group. In addition, intrathrombotic gene expression and the activity of matrix metalloproteinase-9 were increased in the DVT+IR group compared to the DVT group. Furthermore, the DVT+IR group had greater intrathrombotic neovascularization as well as higher gene expression levels of urokinase-type plasminogen activator and tissue-type plasminogen activator than the DVT group. The iron-restricted diet decreased intrathrombotic superoxide production compared to the normal diet. Conclusions These results suggest that dietary iron restriction affects the process of thrombus resolution in DVT. PMID:25962140

Adaptive Value Normalization in the Prefrontal Cortex Is Reduced by Memory Load

PubMed Central

Burke, C. J.; Seifritz, E.; Tobler, P. N.

2017-01-01

Abstract Adaptation facilitates neural representation of a wide range of diverse inputs, including reward values. Adaptive value coding typically relies on contextual information either obtained from the environment or retrieved from and maintained in memory. However, it is unknown whether having to retrieve and maintain context information modulates the brain’s capacity for value adaptation. To address this issue, we measured hemodynamic responses of the prefrontal cortex (PFC) in two studies on risky decision-making. In each trial, healthy human subjects chose between a risky and a safe alternative; half of the participants had to remember the risky alternatives, whereas for the other half they were presented visually. The value of safe alternatives varied across trials. PFC responses adapted to contextual risk information, with steeper coding of safe alternative value in lower-risk contexts. Importantly, this adaptation depended on working memory load, such that response functions relating PFC activity to safe values were steeper with presented versus remembered risk. An independent second study replicated the findings of the first study and showed that similar slope reductions also arose when memory maintenance demands were increased with a secondary working memory task. Formal model comparison showed that a divisive normalization model fitted effects of both risk context and working memory demands on PFC activity better than alternative models of value adaptation, and revealed that reduced suppression of background activity was the critical parameter impairing normalization with increased memory maintenance demand. Our findings suggest that mnemonic processes can constrain normalization of neural value representations. PMID:28462394

Long-Term Study of Heart Rate Variability Responses to Changes in the Solar and Geomagnetic Environment.

PubMed

Alabdulgader, Abdullah; McCraty, Rollin; Atkinson, Michael; Dobyns, York; Vainoras, Alfonsas; Ragulskis, Minvydas; Stolc, Viktor

2018-02-08

This long-term study examined relationships between solar and magnetic factors and the time course and lags of autonomic nervous system (ANS) responses to changes in solar and geomagnetic activity. Heart rate variability (HRV) was recorded for 72 consecutive hours each week over a five-month period in 16 participants in order to examine ANS responses during normal background environmental periods. HRV measures were correlated with solar and geomagnetic variables using multivariate linear regression analysis with Bonferroni corrections for multiple comparisons after removing circadian influences from both datasets. Overall, the study confirms that daily ANS activity responds to changes in geomagnetic and solar activity during periods of normal undisturbed activity and it is initiated at different times after the changes in the various environmental factors and persist over varying time periods. Increase in solar wind intensity was correlated with increases in heart rate, which we interpret as a biological stress response. Increase in cosmic rays, solar radio flux, and Schumann resonance power was all associated with increased HRV and parasympathetic activity. The findings support the hypothesis that energetic environmental phenomena affect psychophysical processes that can affect people in different ways depending on their sensitivity, health status and capacity for self-regulation.

Background staining of visualization systems in immunohistochemistry: comparison of the Avidin-Biotin Complex system and the EnVision+ system.

PubMed

Vosse, Bettine A H; Seelentag, Walter; Bachmann, Astrid; Bosman, Fred T; Yan, Pu

2007-03-01

The aim of this study was to evaluate specific immunostaining and background staining in formalin-fixed, paraffin-embedded human tissues with the 2 most frequently used immunohistochemical detection systems, Avidin-Biotin-Peroxidase (ABC) and EnVision+. A series of fixed tissues, including breast, colon, kidney, larynx, liver, lung, ovary, pancreas, prostate, stomach, and tonsil, was used in the study. Three monoclonal antibodies, 1 against a nuclear antigen (Ki-67), 1 against a cytoplasmic antigen (cytokeratin), and 1 against a cytoplasmic and membrane-associated antigen and a polyclonal antibody against a nuclear and cytoplasmic antigen (S-100) were selected for these studies. When the ABC system was applied, immunostaining was performed with and without blocking of endogenous avidin-binding activity. The intensity of specific immunostaining and the percentage of stained cells were comparable for the 2 detection systems. The use of ABC caused widespread cytoplasmic and rare nuclear background staining in a variety of normal and tumor cells. A very strong background staining was observed in colon, gastric mucosa, liver, and kidney. Blocking avidin-binding capacity reduced background staining, but complete blocking was difficult to attain. With the EnVision+ system no background staining occurred. Given the efficiency of the detection, equal for both systems or higher with EnVision+, and the significant background problem with ABC, we advocate the routine use of the EnVision+ system.

Color normalization for robust evaluation of microscopy images

NASA Astrophysics Data System (ADS)

Švihlík, Jan; Kybic, Jan; Habart, David

2015-09-01

This paper deals with color normalization of microscopy images of Langerhans islets in order to increase robustness of the islet segmentation to illumination changes. The main application is automatic quantitative evaluation of the islet parameters, useful for determining the feasibility of islet transplantation in diabetes. First, background illumination inhomogeneity is compensated and a preliminary foreground/background segmentation is performed. The color normalization itself is done in either lαβ or logarithmic RGB color spaces, by comparison with a reference image. The color-normalized images are segmented using color-based features and pixel-wise logistic regression, trained on manually labeled images. Finally, relevant statistics such as the total islet area are evaluated in order to determine the success likelihood of the transplantation.

Monitoring ventricular function at rest and during exercise with a nonimaging nuclear detector.

PubMed

Wagner, H N; Rigo, P; Baxter, R H; Alderson, P O; Douglass, K H; Housholder, D F

1979-05-01

A portable nonimaging device, the nuclear stethoscope, for measuring beat to beat ventricular time-activity curves in normal people and patients with heart disease, both at rest and during exercise, is being developed and evaluated. The latest device has several operating modes that facilitate left ventricular and background localization, measurement of transit times and automatic calculation and display of left ventricular ejection fraction. The correlation coefficient of left ventricular ejection fraction obtained with the device and with a camera-computer system was 0.92 in 35 subjects. During bicycle exercise the ejection fraction in 15 normal persons increased from 44 to 64 percent (P less than 0.001), whereas among 12 patients with heart disease it was unchanged in 5 and decreased in 7.

Gene Expression Profiling of Multiple Leiomyomata Uteri and Matched Normal Tissue from a Single Patient

PubMed Central

Dimitrova, Irina K.; Richer, Jennifer K.; Rudolph, Michael C.; Spoelstra, Nicole S.; Reno, Elaine M.; Medina, Theresa M.; Bradford, Andrew P.

2009-01-01

Objective To identify differentially expressed genes between fibroid and adjacent normal myometrium in an identical hormonal and genetic background. Design Array analysis of 3 leiomyomata and matched adjacent normal myometrium in a single patient. Setting University of Colorado Hospital. Patient(s) A single female undergoing medically indicated hysterectomy for symptomatic fibroids. Interventions(s) mRNA isolation and microarray analysis, reverse-transcriptase polymerase chain reaction, western blotting and immunohistochemistry. Main Outcome Measure(s) Changes in mRNA and protein levels in leiomyomata and matched normal myometrium. Result(s) Expression of 197 genes was increased and 619 decreased, significantly by at least 2 fold, in leiomyomata relative to normal myometrium. Expression profiles between tumors were similar and normal myometrial samples showed minimal variation. Changes in, and variation of, expression of selected genes were confirmed in additional normal and leiomyoma samples from multiple patients. Conclusion(s) Analysis of multiple tumors from a single patient confirmed changes in expression of genes described in previous, apparently disparate, studies and identified novel targets. Gene expression profiles in leiomyomata are consistent with increased activation of mitogenic pathways and inhibition of apoptosis. Down-regulation of genes implicated in invasion and metastasis, of cancers, was observed in fibroids. This expression pattern may underlie the benign nature of uterine leiomyomata and may aid in the differential diagnosis of leiomyosarcoma. PMID:18672237

PINK1 heterozygous mutations induce subtle alterations in dopamine-dependent synaptic plasticity

PubMed Central

Madeo, G.; Schirinzi, T.; Martella, G.; Latagliata, E.C.; Puglisi, F.; Shen, J.; Valente, E.M.; Federici, M.; Mercuri, N.B.; Puglisi-Allegra, S.; Bonsi, P.; Pisani, A.

2014-01-01

Background Homozygous or compound heterozygous mutations in the PTEN-induced kinase 1 (PINK1) gene are causative of autosomal recessive, early onset PD. Single heterozygous mutations have been repeatedly detected in a subset of patients as well as in non-affected subjects, and their significance has long been debated. Several neurophysiological studies from non-manifesting PINK1 heterozygotes have shown the existence of neural plasticity abnormalities, indicating the presence of specific endophenotypic traits in the heterozygous state. Methods In the present study, we performed a functional analysis of corticostriatal synaptic plasticity in heterozygous PINK1 knock-out (PINK1+/−) mice by a multidisciplinary approach. Results We found that, despite a normal motor behavior, repetitive activation of cortical inputs to striatal neurons failed to induce long-term potentiation (LTP), whereas long-term depression (LTD) was normal. Although nigral dopaminergic neurons exhibited normal morphological and electrophysiological properties with normal responses to dopamine receptor activation, we measured a significantly lower dopamine release in the striatum of PINK1+/−, compared to control mice, suggesting that a decrease in stimulus-evoked dopamine overflow acts as a major determinant for the LTP deficit. Accordingly, pharmacological agents capable of increasing the availability of dopamine in the synaptic cleft restored a normal LTP in heterozygous mice. Moreover, MAO-B inhibitors rescued a physiological LTP and a normal dopamine release. Conclusions Our results provide novel evidence for striatal plasticity abnormalities even in the heterozygous disease state. These alterations might be considered an endophenotype to this monogenic form of PD, and a valid tool to characterize early disease stage and design possible disease-modifying therapies. PMID:24167038

Classification of normal and malignant human gastric mucosa tissue with confocal Raman microspectroscopy and wavelet analysis

NASA Astrophysics Data System (ADS)

Hu, Yaogai; Shen, Aiguo; Jiang, Tao; Ai, Yong; Hu, Jiming

2008-02-01

Thirty-two samples from the human gastric mucosa tissue, including 13 normal and 19 malignant tissue samples were measured by confocal Raman microspectroscopy. The low signal-to-background ratio spectra from human gastric mucosa tissues were obtained by this technique without any sample preparation. Raman spectral interferences include a broad featureless sloping background due to fluorescence and noise. They mask most Raman spectral feature and lead to problems with precision and quantitation of the original spectral information. A preprocessed algorithm based on wavelet analysis was used to reduce noise and eliminate background/baseline of Raman spectra. Comparing preprocessed spectra of malignant gastric mucosa tissues with those of counterpart normal ones, there were obvious spectral changes, including intensity increase at ˜1156 cm -1 and intensity decrease at ˜1587 cm -1. The quantitative criterion based upon the intensity ratio of the ˜1156 and ˜1587 cm -1 was extracted for classification of the normal and malignant gastric mucosa tissue samples. This could result in a new diagnostic method, which would assist the early diagnosis of gastric cancer.

Myb proteins: angels and demons in normal and transformed cells.

PubMed

Zhou, Ye; Ness, Scott A

2011-01-01

A key regulator of proliferation, differentiation and cell fate, the c-Myb transcription factor regulates the expression of hundreds of genes and is in turn regulated by numerous pathways and protein interactions. However, the most unique feature of c-Myb is that it can be converted into an oncogenic transforming protein through a few mutations that completely change its activity and specificity. The c-Myb protein is a myriad of interactions and activities rolled up in a protein that controls proliferation and differentiation in many different cell types. Here we discuss the background and recent progress that have led to a better understanding of this complex protein, and outline the questions that have yet to be answered.

Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model

PubMed Central

Sreemantula, Satyanarayana; Nammi, Srinivas; Kolanukonda, Rajabhanu; Koppula, Sushruta; Boini, Krishna M

2005-01-01

Background The aerial parts of Vitis vinifera (common grape or European grape) have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, the seed extract of V. vinifera was evaluated for antistress activity in normal and stress induced rats. Furthermore, the extract was studied for nootropic activity in rats and in-vitro antioxidant potential to correlate its antistress activity. Methods For the evaluation of antistress activity, groups of rats (n = 6) were subjected to forced swim stress one hour after daily treatment of V. vinifera extract. Urinary vanillylmandelic acid (VMA) and ascorbic acid were selected as non-invasive biomarkers to assess the antistress activity. The 24 h urinary excretion of vanillylmandelic acid (VMA) and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. The nootropic activity of the extract as determined from acquisition, retention and retrieval in rats was studied by conditioned avoidance response using Cook's pole climbing apparatus. The in vitro antioxidant activity was determined based on the ability of V. vinifera to scavenge hydroxyl radicals. Results Daily administration of V. vinifera at doses of 100, 200 and 300 mg/kg body weight one hour prior to induction of stress inhibited the stress induced urinary biochemical changes in a dose dependent manner. However, no change in the urinary excretion of VMA and ascorbic acid was observed in normal animals at all the doses studied. The cognition, as determined by the acquisition, retention and recovery in rats was observed to be dose dependent. The extract also produced significant inhibition of hydroxyl radicals in comparison to ascorbic acid in a dose dependent manner. Conclusion The present study provides scientific support for the antistress (adaptogenic), antioxidant and nootropic activities of V. vinifera seed extract and substantiate the traditional claims for the usage of grape fruits and seeds in stress induced disorders. PMID:15656916

A comparison of vowel normalization procedures for language variation research

NASA Astrophysics Data System (ADS)

Adank, Patti; Smits, Roel; van Hout, Roeland

2004-11-01

An evaluation of vowel normalization procedures for the purpose of studying language variation is presented. The procedures were compared on how effectively they (a) preserve phonemic information, (b) preserve information about the talker's regional background (or sociolinguistic information), and (c) minimize anatomical/physiological variation in acoustic representations of vowels. Recordings were made for 80 female talkers and 80 male talkers of Dutch. These talkers were stratified according to their gender and regional background. The normalization procedures were applied to measurements of the fundamental frequency and the first three formant frequencies for a large set of vowel tokens. The normalization procedures were evaluated through statistical pattern analysis. The results show that normalization procedures that use information across multiple vowels (``vowel-extrinsic'' information) to normalize a single vowel token performed better than those that include only information contained in the vowel token itself (``vowel-intrinsic'' information). Furthermore, the results show that normalization procedures that operate on individual formants performed better than those that use information across multiple formants (e.g., ``formant-extrinsic'' F2-F1). .

A comparison of vowel normalization procedures for language variation research.

PubMed

Adank, Patti; Smits, Roel; van Hout, Roeland

2004-11-01

An evaluation of vowel normalization procedures for the purpose of studying language variation is presented. The procedures were compared on how effectively they (a) preserve phonemic information, (b) preserve information about the talker's regional background (or sociolinguistic information), and (c) minimize anatomical/physiological variation in acoustic representations of vowels. Recordings were made for 80 female talkers and 80 male talkers of Dutch. These talkers were stratified according to their gender and regional background. The normalization procedures were applied to measurements of the fundamental frequency and the first three formant frequencies for a large set of vowel tokens. The normalization procedures were evaluated through statistical pattern analysis. The results show that normalization procedures that use information across multiple vowels ("vowel-extrinsic" information) to normalize a single vowel token performed better than those that include only information contained in the vowel token itself ("vowel-intrinsic" information). Furthermore, the results show that normalization procedures that operate on individual formants performed better than those that use information across multiple formants (e.g., "formant-extrinsic" F2-F1).

The Formation of COINS: Equity and Inclusion in SDSS

NASA Astrophysics Data System (ADS)

Schmidt, Sarah J.; Sanchez-Gallego, Jose Ramon; Chanover, Nancy J.; Holley-Bockelmann, Kelly; Lucatello, Sara; Aragon-Salamanca, Alfonso; Belfiore, Francesco; Cherinka, Brian; Feuillet, Diane; Jones, Amy; Masters, Karen; Simmons, Audrey; Ross, Ashley; Stassun, Keivan G.; Tayar, Jamie

2017-01-01

In the era of large surveys, collaborations like the Sloan Digital Sky Survey (SDSS) are becoming a new normal for many scientists, and collaboration policies and climate have a considerable affect on scientific careers. As such, it is essential that collaborations actively strive to include all scientists regardless of gender, gender identity, race, ethnicity, sexual orientation, disability, career stage, geographic location, economic background, social and cultural backgrounds, and all possible intersections thereof. We report on the formation and progress of the Committee On INclusiveness in the SDSS (COINS). COINS was formed to assess the SDSS-IV project and collaboration's climate and demographics, to recommend new policies or practices with regard to increasing inclusiveness, and to assist in the implementation of these new activities where necessary. We report on our current activities, which include ongoing support for the SDSS Research Experience for Undergraduates program, support for the SDSS Faculty and Student Teams initiative, administering and analyzing the SDSS demographic surveys, working towards collaboration meeting inclusiveness and accessibility, and adopting strategies for integrating and mentoring new members. We welcome input from SDSS members and non-members about how to work towards a more equitable and inclusive collaboration.

A phenanthrene derived PARP inhibitor is an extra-centrosomes de-clustering agent exclusively eradicating human cancer cells

PubMed Central

2011-01-01

Background Cells of most human cancers have supernumerary centrosomes. To enable an accurate chromosome segregation and cell division, these cells developed a yet unresolved molecular mechanism, clustering their extra centrosomes at two poles, thereby mimicking mitosis in normal cells. Failure of this bipolar centrosome clustering causes multipolar spindle structures and aberrant chromosomes segregation that prevent normal cell division and lead to 'mitotic catastrophe cell death'. Methods We used cell biology and biochemical methods, including flow cytometry, immunocytochemistry and live confocal imaging. Results We identified a phenanthrene derived PARP inhibitor, known for its activity in neuroprotection under stress conditions, which exclusively eradicated multi-centrosomal human cancer cells (mammary, colon, lung, pancreas, ovarian) while acting as extra-centrosomes de-clustering agent in mitosis. Normal human proliferating cells (endothelial, epithelial and mesenchymal cells) were not impaired. Despite acting as PARP inhibitor, the cytotoxic activity of this molecule in cancer cells was not attributed to PARP inhibition alone. Conclusion We identified a water soluble phenanthridine that exclusively targets the unique dependence of most human cancer cells on their supernumerary centrosomes bi-polar clustering for their survival. This paves the way for a new selective cancer-targeting therapy, efficient in a wide range of human cancers. PMID:21943092

Role of 4-hydroxynonenal in chemopreventive activities of sulforaphane

PubMed Central

Sharma, Rajendra; Sharma, Abha; Chaudhary, Pankaj; Sahu, Mukesh; Jaiswal, Shailesh; Awasthi, Sanjay; Awasthi, Yogesh C.

2012-01-01

Chemoprevention of cancer via herbal and dietary supplements is a logical approach to combat cancer and presently it is an attractive area of research investigations. Over the years, the use of isothiocyanates, such as sulforaphane (SFN) found in cruciferous vegetables, has been advocated as chemopreventive agents and their efficacy has been demonstrated in cell lines and animal models. In-vivo studies with SFN suggest that besides protecting normal healthy cells from environmental carcinogens it also exhibits cytotoxicity and apoptotic effects against various cancer cell types. Among several mechanisms for the chemopreventive activity of SFN against chemical carcinogenesis, its effect on drug metabolizing enzymes that causes activation/ neutralization of carcinogenic metabolites is well established. Recent studies suggest that SFN exerts its selective cytotoxicity to cancer cells via reactive oxygen species (ROS)-mediated generation of lipid peroxidation (LPO) products particularly 4-hydroxynonenal (HNE). Against the background of the known biochemical effects of SFN on normal and cancer cells, in this article we have reviewed the underlying molecular mechanisms responsible for the overall chemopreventive effects of SFN focusing on the role of HNE in these mechanisms that may also contribute to its selective cytotoxicity to cancer cells. PMID:22579574

Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients.

PubMed

Ogawa, Erika; Shimura, Masaru; Fushimi, Takuya; Tajika, Makiko; Ichimoto, Keiko; Matsunaga, Ayako; Tsuruoka, Tomoko; Ishige, Mika; Fuchigami, Tatsuo; Yamazaki, Taro; Mori, Masato; Kohda, Masakazu; Kishita, Yoshihito; Okazaki, Yasushi; Takahashi, Shori; Ohtake, Akira; Murayama, Kei

2017-09-01

Leigh syndrome (LS) is a progressive neurodegenerative disorder of infancy and early childhood. It is clinically diagnosed by typical manifestations and characteristic computed tomography (CT) or magnetic resonance imaging (MRI) studies. Unravelling mitochondrial respiratory chain (MRC) dysfunction behind LS is essential for deeper understanding of the disease, which may lead to the development of new therapies and cure. The aim of this study was to evaluate the clinical validity of various diagnostic tools in confirming MRC disorder in LS and Leigh-like syndrome (LL). The results of enzyme assays, molecular analysis, and cellular oxygen consumption rate (OCR) measurements were examined. Of 106 patients, 41 were biochemically and genetically verified, and 34 had reduced MRC activity but no causative mutations. Seven patients with normal MRC complex activities had mutations in the MT-ATP6 gene. Five further patients with normal activity in MRC were identified with causative mutations. Conversely, 12 out of 60 enzyme assays performed for genetically verified patients returned normal results. No biochemical or genetic background was confirmed for 19 patients. OCR was reduced in ten out of 19 patients with negative enzyme assay results. Inconsistent enzyme assay results between fibroblast and skeletal muscle biopsy samples were observed in 33% of 37 simultaneously analyzed cases. These data suggest that highest diagnostic rate is reached using a combined enzymatic and genetic approach, analyzing more than one type of biological materials where suitable. Microscale oxygraphy detected MRC impairment in 50% cases with no defect in MRC complex activities.

The transcriptional activator ZNF143 is essential for normal development in zebrafish

PubMed Central

2012-01-01

Background ZNF143 is a sequence-specific DNA-binding protein that stimulates transcription of both small RNA genes by RNA polymerase II or III, or protein-coding genes by RNA polymerase II, using separable activating domains. We describe phenotypic effects following knockdown of this protein in developing Danio rerio (zebrafish) embryos by injection of morpholino antisense oligonucleotides that target znf143 mRNA. Results The loss of function phenotype is pleiotropic and includes a broad array of abnormalities including defects in heart, blood, ear and midbrain hindbrain boundary. Defects are rescued by coinjection of synthetic mRNA encoding full-length ZNF143 protein, but not by protein lacking the amino-terminal activation domains. Accordingly, expression of several marker genes is affected following knockdown, including GATA-binding protein 1 (gata1), cardiac myosin light chain 2 (cmlc2) and paired box gene 2a (pax2a). The zebrafish pax2a gene proximal promoter contains two binding sites for ZNF143, and reporter gene transcription driven by this promoter in transfected cells is activated by this protein. Conclusions Normal development of zebrafish embryos requires ZNF143. Furthermore, the pax2a gene is probably one example of many protein-coding gene targets of ZNF143 during zebrafish development. PMID:22268977

National Study of Changes in Community Access to School Physical Activity Facilities: The School Health Policies and Programs Study

PubMed Central

Evenson, Kelly R.; Wen, Fang; Lee, Sarah M.; Heinrich, Katie M.; Eyler, Amy

2016-01-01

Background A Healthy People 2010 developmental objective (22-12) was set to increase the proportion of the nation’s public and private schools that provide access to their physical activity spaces and facilities for all persons outside of normal school hours. The purpose of this study was to describe the prevalence of indoor and outdoor facilities at schools and the availability of those facilities to the public in 2000 and 2006. Methods In 2000 and 2006, the School Health Policies and Programs Study (SHPPS) was conducted in each state and in randomly selected districts, schools, and classrooms. This analysis focused on the school level questionnaire from a nationally representative sample of public and nonpublic elementary, middle, and high schools (n = 921 in 2000 and n = 984 in 2006). Results No meaningful changes in the prevalence of access to school physical activity facilities were found from 2000 to 2006, for youth or adult community sports teams, classes, or open gym. Conclusions These national data indicate a lack of progress from 2000 and 2006 toward increasing the proportion of the nation’s public and private schools that provide access to their physical activity facilities for all persons outside of normal school hours. PMID:20440007

An introduction to the BANNING design automation system for shuttle microelectronic hardware development

NASA Technical Reports Server (NTRS)

Mcgrady, W. J.

1979-01-01

The BANNING MOS design system is presented. It complements rather than supplant the normal design activities associated with the design and fabrication of low-power digital electronic equipment. BANNING is user-oriented and requires no programming experience to use effectively. It provides the user a simulation capability to aid in his circuit design and it eliminates most of the manual operations involved in the layout and artwork generation of integrated circuits. An example of its operation is given and some additional background reading is provided.

Astronaut Musgrave performing EVA during STS-6

NASA Technical Reports Server (NTRS)

1983-01-01

Views of Mission Specialist F. Story Musgrave performing an extravehicular activity (EVA) during the STS-6 mission. In this view, Musgrave uses hand holds in the payload bay door hinge line to move towards the aft payload bay (30215); Musgrave conducts a simulation of a contingency EVA in the aft payload bay. This was designed to return the inertial upper stage (IUS) support equipment's tilt table device to its normal stowed configuration in the event of failure of an automatic system. A cloud-covered earth can be seen in the background (30216).

Enzyme-Sensitive MR Imaging Targeting Myeloperoxidase Identifies Active Inflammation in Experimental Rabbit Atherosclerotic Plaques

PubMed Central

Ronald, John A.; Chen, John W.; Chen, Yuanxin; Hamilton, Amanda M.; Rodriguez, Elisenda; Reynolds, Fred; Hegele, Robert A.; Rogers, Kem A.; Querol, Manel; Bogdanov, Alexei; Weissleder, Ralph; Rutt, Brian K.

2009-01-01

Background Inflammation undermines the stability of atherosclerotic plaques, rendering them susceptible to acute rupture, the cataclysmic event that underlies clinical expression of this disease. Myeloperoxidase (MPO) is a central inflammatory enzyme secreted by activated macrophages, and is involved in multiple stages of plaque destabilization and patient outcome. We report here that a unique functional in vivo magnetic resonance (MR) agent can visualize MPO activity in atherosclerotic plaques in a rabbit model. Methods and Results We performed MR imaging of the thoracic aorta of New Zealand white (NZW) rabbits fed a cholesterol (n=11) or normal (n=4) diet up to 2 hours after injection of the MPO sensor bis-5HT-DTPA(Gd) (MPO(Gd)), the conventional agent, DTPA(Gd), or an MPO (Gd) analog, bis-tyr-DTPA(Gd), as controls. Delayed MPO(Gd) images (2 hour post injection) showed focal areas of increased contrast (>2-fold) in diseased wall, but not in normal wall (p=0.84), compared to both DTPA(Gd) (n=11; p<0.001) and bis-tyr-DTPA(Gd) (n=3; p<0.05). Biochemical assays confirmed that diseased wall possessed three-fold elevated MPO activity compared to normal wall (p<0.01). Areas detected by MPO(Gd) imaging co-localized and correlated with MPO-rich areas infiltrated by macrophages on histopathological evaluations (r=0.91, p<0.0001). While macrophages were the main source of MPO, not all macrophages secreted MPO, suggesting that distinct subpopulations contribute differently to atherogenesis and supporting our functional approach. Conclusions Our study represents a unique approach in the detection of inflammation in atherosclerotic plaques by examining macrophage function and the activity of an effector enzyme, to noninvasively provide both anatomic and functional information in vivo. PMID:19652086

Abnormal Chloride Homeostasis in the Substancia Nigra Pars Reticulata Contributes to Locomotor Deficiency in a Model of Acute Liver Injury

PubMed Central

Wei, Yan-Yan; Chen, Jing; Dou, Ke-Feng; Wang, Ya-Yun

2013-01-01

Background Altered chloride homeostasis has been thought to be a risk factor for several brain disorders, while less attention has been paid to its role in liver disease. We aimed to analyze the involvement and possible mechanisms of altered chloride homeostasis of GABAergic neurons within the substantia nigra pars reticulata (SNr) in the motor deficit observed in a model of encephalopathy caused by acute liver failure, by using glutamic acid decarboxylase 67 - green fluorescent protein knock-in transgenic mice. Methods Alterations in intracellular chloride concentration in GABAergic neurons within the SNr and changes in the expression of two dominant chloride homeostasis-regulating genes, KCC2 and NKCC1, were evaluated in mice with hypolocomotion due to hepatic encephalopathy (HE). The effects of pharmacological blockade and/or activation of KCC2 and NKCC1 functions with their specific inhibitors and/or activators on the motor activity were assessed. Results In our mouse model of acute liver injury, chloride imaging indicated an increase in local intracellular chloride concentration in SNr GABAergic neurons. In addition, the mRNA and protein levels of KCC2 were reduced, particularly on neuronal cell membranes; in contrast, NKCC1 expression remained unaffected. Furthermore, blockage of KCC2 reduced motor activity in the normal mice and led to a further deteriorated hypolocomotion in HE mice. Blockade of NKCC1 was not able to normalize motor activity in mice with liver failure. Conclusion Our data suggest that altered chloride homeostasis is likely involved in the pathophysiology of hypolocomotion following HE. Drugs aimed at restoring normal chloride homeostasis would be a potential treatment for hepatic failure. PMID:23741482

Aerobic Steps As Measured by Pedometry and Their Relation to Central Obesity

PubMed Central

DUCHEČKOVÁ, Petra; FOREJT, Martin

2014-01-01

Abstract Background The purpose of this study was to examine the relation between daily steps and aerobic steps, and anthropometric variables, using the waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). Methods The participants in this cross-sectional study were taken the measurements of by a trained anthropologist and then instructed to wear an Omron pedometer for seven consecutive days. A series of statistical tests (Mann-Whitney U test, Kruskal-Wallis ANOVA, multiple comparisons of z’ values and contingency tables) was performed in order to assess the relation between daily steps and aerobic steps, and anthropometric variables. Results A total of 507 individuals (380 females and 127 males) participated in the study. The average daily number of steps and aerobic steps was significantly lower in the individuals with risky WHR and WHtR as compared to the individuals with normal WHR (P=0.005) and WHtR (P=0.000). A comparison of age and anthropometric variables across aerobic steps activity categories was statistically significant for all the studied parameters. According to the contingency tables for normal steps, there is a 5.75x higher risk in the low-activity category of having WHtR>0.50 as compared to the high-activity category. Conclusions Both normal and aerobic steps are significantly associated with central obesity and other body composition variables. This result is important for older people, who are more likely to perform low-intensity activities rather than moderate- or high-intensity activities. Our results also indicate that risk of having WHtR>0.50 can be reduced by almost 6x by increasing daily steps over 8985 steps per day. PMID:25927036

Association between parenting practices and children's dietary intake, activity behavior and development of body mass index: the KOALA Birth Cohort Study

PubMed Central

2011-01-01

Background Insights into the effects of energy balance-related parenting practices on children's diet and activity behavior at an early age is warranted to determine which practices should be recommended and to whom. The purpose of this study was to examine child and parent background correlates of energy balance-related parenting practices at age 5, as well as the associations of these practices with children's diet, activity behavior, and body mass index (BMI) development. Methods Questionnaire data originated from the KOALA Birth Cohort Study for ages 5 (N = 2026) and 7 (N = 1819). Linear regression analyses were used to examine the association of child and parent background characteristics with parenting practices (i.e., diet- and activity-related restriction, monitoring and stimulation), and to examine the associations between these parenting practices and children's diet (in terms of energy intake, dietary fiber intake, and added sugar intake) and activity behavior (i.e., physical activity and sedentary time) at age 5, as well as BMI development from age 5 to age 7. Moderation analyses were used to examine whether the associations between the parenting practices and child behavior depended on child characteristics. Results Several child and parent background characteristics were associated with the parenting practices. Dietary monitoring, stimulation of healthy intake and stimulation of physical activity were associated with desirable energy balance-related behaviors (i.e., dietary intake and/or activity behavior) and desirable BMI development, whereas restriction of sedentary time showed associations with undesirable behaviors and BMI development. Child eating style and weight status, but not child gender or activity style, moderated the associations between parenting practices and behavior. Dietary restriction and monitoring showed weaker, or even undesirable associations for children with a deviant eating style, whereas these practices showed associations with desirable behavior for normal eaters. By contrast, stimulation to eat healthy worked particularly well for children with a deviant eating style or a high BMI. Conclusion Although most energy balance-related parenting practices were associated with desirable behaviors, some practices showed associations with undesirable child behavior and weight outcomes. Only parental stimulation showed desirable associations with regard to both diet and activity behavior. The interaction between parenting and child characteristics in the association with behavior calls for parenting that is tailored to the individual child. PMID:21401954

Viability and Burden of Leishmania in Extralesional Sites during Human Dermal Leishmaniasis

PubMed Central

Romero, Ibeth; Téllez, Jair; Suárez, Yazmín; Cardona, Maria; Figueroa, Roger; Zelazny, Adrian; Gore Saravia, Nancy

2010-01-01

Background The clinical and epidemiological significance of Leishmania DNA in extralesional sites is obscured by uncertainty of whether the DNA derives from viable parasites. To examine dissemination of Leishmania during active disease and the potential participation of human infection in transmission, Leishmania 7SLRNA was exploited to establish viability and estimate parasite burden in extralesional sites of dermal leishmaniasis patients. Methods The feasibility of discriminating parasite viability by PCR of Leishmania 7SLRNA was evaluated in relation with luciferase activity of luc transfected intracellular amastigotes in dose-response assays of Glucantime cytotoxicity. Monocytes, tonsil swabs, aspirates of normal skin and lesions of 28 cutaneous and 2 mucocutaneous leishmaniasis patients were screened by kDNA amplification/Southern blot. Positive samples were analyzed by quantitative PCR of Leishmania 7SLRNA genes and transcripts. Results 7SLRNA amplification coincided with luciferase activity, confirming discrimination of parasite viability. Of 22 patients presenting kDNA in extralesional samples, Leishmania 7SLRNA genes or transcripts were detected in one or more kDNA positive samples in 100% and 73% of patients, respectively. Gene and transcript copy number amplified from extralesional tissues were comparable to lesions. 7SLRNA transcripts were detected in 13/19 (68%) monocyte samples, 5/12 (42%) tonsil swabs, 4/11 (36%) normal skin aspirates, and 22/25 (88%) lesions; genes were quantifiable in 15/19 (79%) monocyte samples, 12/13 (92%) tonsil swabs, 8/11 (73%) normal skin aspirates. Conclusion Viable parasites are present in extralesional sites, including blood monocytes, tonsils and normal skin of dermal leishmaniasis patients. Leishmania 7SLRNA is an informative target for clinical and epidemiologic investigations of human leishmaniasis. PMID:20856851

Paroxysmal anal hyperkinesis: a characteristic feature of proctalgia fugax.

PubMed Central

Rao, S S; Hatfield, R A

1996-01-01

BACKGROUND AND AIMS: Proctalgia fugax is a common problem, yet its pathophysiology is poorly understood. The objective was to characterise colorectal disturbances in a paraplegic patient with a 10 year history of proctalgia fugax that began two years after an attack of transverse myelitis. METHODS: Standard anorectal manometry and prolonged 33 hour ambulatory colonic manometry at six sites in the colon were performed together with myoelectrical recording of the anus. Provocative tests designed to simulate psychological and physical stress and two types of meals were included. RESULTS: Anorectal manometry showed normal internal sphincter tone and normal rectoanal inhibitory reflex but an inability to squeeze or to bear down or to expel a simulated stool. Rectal sensation (up to 360 ml inflation) was absent. Pudendal nerve latency was prolonged (4.5 ms (normal < 2.2 ms). During colonic manometry, the patient reported 27 episodes of pain, of which 23 (85%) were associated with bursts (1-60 min) of a high amplitude (0.5 to > 3.2 mv), high frequency (5-50/min) anal myoelectrical activity, particularly after stress tests, meals, and at night. The myoelectrical disturbance only occurred with proctalgia. Intermittently, 16 bursts of 3 cycles/ min phasic rectal contractions were seen, but only six were associated with proctalgia. Colonic motility was reduced compared with normal subjects. CONCLUSIONS: The temporal association between a high amplitude, high frequency myoelectrical activity of the anal sphincter, and the occurrence of proctalgia suggests that paroxysmal hyperkinesis of the anus may cause proctalgia fugax. PMID:8944574

Haplo-Insufficiency of MPK3 in MPK6 Mutant Background Uncovers a Novel Function of These Two MAPKs in Arabidopsis Ovule Development[W

PubMed Central

Wang, Huachun; Liu, Yidong; Bruffett, Kristin; Lee, Justin; Hause, Gerd; Walker, John C.; Zhang, Shuqun

2008-01-01

The plant life cycle includes diploid sporophytic and haploid gametophytic generations. Female gametophytes (embryo sacs) in higher plants are embedded in specialized sporophytic structures (ovules). Here, we report that two closely related mitogen-activated protein kinases in Arabidopsis thaliana, MPK3 and MPK6, share a novel function in ovule development: in the MPK6 mutant background, MPK3 is haplo-insufficient, giving female sterility when heterozygous. By contrast, in the MPK3 mutant background, MPK6 does not show haplo-insufficiency. Using wounding treatment, we discovered gene dosage–dependent activation of MPK3 and MPK6. In addition, MPK6 activation is enhanced when MPK3 is null, which may help explain why mpk3−/− mpk6+/− plants are fertile. Genetic analysis revealed that the female sterility of mpk3+/− mpk6−/− plants is a sporophytic effect. In mpk3+/− mpk6−/− mutant plants, megasporogenesis and megagametogenesis are normal and the female gametophyte identity is correctly established. Further analysis demonstrates that the mpk3+/− mpk6−/− ovules have abnormal integument development with arrested cell divisions at later stages. The mutant integuments fail to accommodate the developing embryo sac, resulting in the embryo sacs being physically restricted and female reproductive failure. Our results highlight an essential function of MPK3 and MPK6 in promoting cell division in the integument specifically during ovule development. PMID:18364464

Reduction of spontaneous somatic mutation frequency by a low-dose X irradiation of Drosophila larvae and possible involvement of DNA single-strand damage repair.

PubMed

Koana, Takao; Takahashi, Takashi; Tsujimura, Hidenobu

2012-03-01

The third instar larvae of Drosophila were irradiated with X rays, and the somatic mutation frequency in their wings was measured after their eclosion. In the flies with normal DNA repair and apoptosis functions, 0.2 Gy irradiation at 0.05 Gy/min reduced the frequency of the so-called small spot (mutant cell clone with reduced reproductive activity) compared with that in the sham-irradiated flies. When apoptosis was suppressed using the baculovirus p35 gene, the small spot frequency increased four times in the sham-irradiated control group, but the reduction by the 0.2-Gy irradiation was still evident. In a non-homologous end joining-deficient mutant, the small spot frequency was also reduced by 0.2 Gy radiation. In a mutant deficient in single-strand break repair, no reduction in the small spot frequency by 0.2 Gy radiation was observed, and the small spot frequency increased with the radiation dose. Large spot (mutant cell clone with normal reproductive activity) frequency was not affected by suppression of apoptosis and increased monotonically with radiation dose in wild-type larvae and in mutants for single- or double-strand break repair. It is hypothesized that some of the small spots resulted from single-strand damage and, in wild-type larvae, 0.2 Gy radiation activated the normal single-strand break repair gene, which reduced the background somatic mutation frequency.

Detection and characterisation of multi-drug resistance protein 1 (MRP-1) in human mitochondria

PubMed Central

Roundhill, E A; Burchill, S A

2012-01-01

Background: Overexpression of plasma membrane multi-drug resistance protein 1 (MRP-1) can lead to multidrug resistance. In this study, we describe for the first time the expression of mitochondrial MRP-1 in untreated human normal and cancer cells and tissues. Methods: MRP-1 expression and subcellular localisation in normal and cancer cells and tissues was examined by differential centrifugation and western blotting, and immunofluorescence microscopy. Viable mitochondria were isolated and MRP-1 efflux activity measured using the calcein-AM functional assay. MRP-1 expression was increased using retroviral infection and specific overexpression confirmed by RNA array. Cell viability was determined by trypan blue exclusion and annexin V-propidium iodide labelling of cells. Results: MRP-1 was detected in the mitochondria of cancer and normal cells and tissues. The efflux activity of mitochondrial MRP-1 was more efficient (55–64%) than that of plasma membrane MRP-1 (11–22% P<0.001). Induced MRP-1 expression resulted in a preferential increase in mitochondrial MRP-1, suggesting selective targeting to this organelle. Treatment with a non-lethal concentration of doxorubicin (0.85 n, 8 h) increased mitochondrial and plasma membrane MRP-1, increasing resistance to MRP-1 substrates. For the first time, we have identified MRP-1 with efflux activity in human mitochondria. Conclusion: Mitochondrial MRP-1 may be an exciting new therapeutic target where historically MRP-1 inhibitor strategies have limited clinical success. PMID:22353810

Glioma Invasiveness Responds Variably to Irradiation in a Co-Culture Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, Jean L.; Haas-Kogan, Daphne A.; Department of Neurological Surgery, University of California-San Francisco, San Francisco, CA

2007-11-01

Purpose: We developed a co-culture system to quantitate the growth and invasion of human malignant gliomas into a background of confluent normal human astrocytes, then used this assay to assess independently the effects of irradiating both cell types on glioma invasion. Methods and Materials: Enhanced green fluorescent protein (EGFP)-labeled immortalized human astrocytes, human malignant glioma cells, or transformed human astrocytes were focally plated onto a confluent layer of normal human astrocytes, and the invasiveness of EGFP-labeled cells was scored after 96 h. To address the consequences of irradiation on glioma invasion, the invasiveness of irradiated glioma cell lines and irradiatedmore » astrocytic backgrounds was assessed. Fluorescence-activated cell sorting was used to quantitate the total number of EGFP-labeled cells. Results: Growth in the co-culture assay consistently reflected transformation states of the plated cells. Immortalized, but untransformed human astrocytes failed even to establish growth on confluent normal human astrocytes. In contrast, all malignant human glioma cell lines and transformed human astrocytes demonstrated various degrees of infiltration into the astrocytic bed. Irradiation failed to alter the invasiveness of U87, A172, and U373. A 1-Gy dose slightly reduced the invasiveness of U251 MG by 75% (p < 0.05 by one-way analysis of variance and post hoc Neuman-Keuls), without reducing total cell numbers. Independently irradiating the human astrocytic bed did not alter the invasiveness of nonirradiated U251, whereas the matrix metalloproteinase (MMP) inhibitor GM6001 reduced U251 invasiveness in the co-culture assay. Conclusions: Growth in the co-culture assay reflects the transformation status and provides a useful in vitro model for assessing invasiveness. Human glioma invasiveness in the co-culture model responds variably to single low-dose fractions. MMP activity promotes invasiveness in the co-culture model. Reduced invasiveness in irradiated U251 appears to be mediated by MMP-independent mechanisms.« less

A comprehensive prediction and evaluation method of pilot workload

PubMed Central

Feng, Chuanyan; Wanyan, Xiaoru; Yang, Kun; Zhuang, Damin; Wu, Xu

2018-01-01

BACKGROUND: The prediction and evaluation of pilot workload is a key problem in human factor airworthiness of cockpit. OBJECTIVE: A pilot traffic pattern task was designed in a flight simulation environment in order to carry out the pilot workload prediction and improve the evaluation method. METHODS: The prediction of typical flight subtasks and dynamic workloads (cruise, approach, and landing) were built up based on multiple resource theory, and a favorable validity was achieved by the correlation analysis verification between sensitive physiological data and the predicted value. RESULTS: Statistical analysis indicated that eye movement indices (fixation frequency, mean fixation time, saccade frequency, mean saccade time, and mean pupil diameter), Electrocardiogram indices (mean normal-to-normal interval and the ratio between low frequency and sum of low frequency and high frequency), and Electrodermal Activity indices (mean tonic and mean phasic) were all sensitive to typical workloads of subjects. CONCLUSION: A multinominal logistic regression model based on combination of physiological indices (fixation frequency, mean normal-to-normal interval, the ratio between low frequency and sum of low frequency and high frequency, and mean tonic) was constructed, and the discriminate accuracy was comparatively ideal with a rate of 84.85%. PMID:29710742

The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide

PubMed Central

Soscia, Stephanie J.; Kirby, James E.; Washicosky, Kevin J.; Tucker, Stephanie M.; Ingelsson, Martin; Hyman, Bradley; Burton, Mark A.; Goldstein, Lee E.; Duong, Scott; Tanzi, Rudolph E.; Moir, Robert D.

2010-01-01

Background The amyloid β-protein (Aβ) is believed to be the key mediator of Alzheimer's disease (AD) pathology. Aβ is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, Aβ has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities. Methodology/Principal Findings Here, we provide data supporting an in vivo function for Aβ as an antimicrobial peptide (AMP). Experiments used established in vitro assays to compare antimicrobial activities of Aβ and LL-37, an archetypical human AMP. Findings reveal that Aβ exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue Aβ levels. Consistent with Aβ-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-Aβ antibodies. Conclusions/Significance Our findings suggest Aβ is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of Aβ-mediated pathology and has important implications for ongoing and future AD treatment strategies. PMID:20209079

Protective activity of Panduratin A against Thioacetamide-induced oxidative damage: demonstration with in vitro experiments using WRL-68 liver cell line

PubMed Central

2013-01-01

Background Chalcone Panduratin A (PA) has been known for its antioxidant property, but its merits against oxidative damage in liver cells has yet to be investigated. Hence, the paper aimed at accomplishing this task with normal embryonic cell line WRL-68. Methods PA was isolated from Boesenbergia rotunda rhizomes and its 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and ferric reducing power (FRAP) activities were measured in comparison with that of the standard reference drug Silymarin (SI). Oxidative damage was induced by treating the cells with 0.04 g/ml of toxic thioacetamide for 60 minutes followed by treatment with 1, 10 and 100 μg/ml concentrations of either PA or SI. The severities of oxidative stress in the control and experimental groups of cells were measured by Malondialdehyde (MDA) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. Results PA exhibited an acceptable DPPH scavenging and FRAP activities close to that of Silymarin. Treating the injured cells with PA significantly reduced the MDA level and increased the cell viability, comparable to SI. The activities of SOD, CAT and GPx were significantly elevated in the PA-treated cells in a dose dependent manner and again similar to SI. Conclusion Collectively, data suggested that PA has capacity to protect normal liver cells from oxidative damage, most likely via its antioxidant scavenging ability. PMID:24156366

Background Error Correlation Modeling with Diffusion Operators

DTIC Science & Technology

2013-01-01

RESPONSIBLE PERSON 19b. TELEPHONE NUMBER (Include area code) 07-10-2013 Book Chapter Background Error Correlation Modeling with Diffusion Operators...normalization Unclassified Unclassified Unclassified UU 27 Max Yaremchuk (228) 688-5259 Reset Chapter 8 Background error correlation modeling with diffusion ...field, then a structure like this simulates enhanced diffusive transport of model errors in the regions of strong cur- rents on the background of

A Teleconnection between the West Siberian Plain and the ENSO Region

NASA Astrophysics Data System (ADS)

Liess, S.; Agrawal, S.; Chatterjee, S.; Kumar, V.

2017-12-01

This study presents a mechanism that links the El Niño/Southern Oscillation (ENSO) to extratropical waves that are deflected from the Northern Hemisphere polar regions and travel southeastward over Central Asia toward the west Pacific warm pool during northern winter. The initial wave pattern resembles the well-known East Atlantic-West Russia pattern. Here we show its influence on the ENSO region. We identify a tripole pattern between the West Siberian Plain and the two centers of action of ENSO with a graph-based approach. It indicates that the background state of ENSO with respect to global sea level pressure (SLP) has a significant negative correlation to the West Siberian Plain. The correlation with the background state, which is defined by the sum of the two centers of action of ENSO, is higher than each of the pairwise correlations with either of the ENSO centers alone. We define the centers with a clustering algorithm that detects regions with similar characteristics. The normalized monthly SLP time series for the two centers of ENSO (around Darwin, Australia and Tahiti) are area-averaged and the sum of both regions is considered as the background state of ENSO. This wave train can be detected throughout the troposphere and the lower stratosphere. Its origins can be traced back to atmospheric wave activity triggered by convection over the subtropical North Atlantic that emanates wave activity toward the West Siberian Plain. The same wave train also propagates to the central Pacific Ocean around Tahiti and can be used to predict the background state over the ENSO region. This background state also modifies the subtropical bridge between the tropical east Pacific and the subtropical North Atlantic, thus leading to a circumglobal wave train.

Activities of daily living measured by the Harvard Automated Phone Task track with cognitive decline over time in non-demented elderly

PubMed Central

Marshall, Gad A.; Aghjayan, Sarah L.; Dekhtyar, Maria; Locascio, Joseph J.; Jethwani, Kamal; Amariglio, Rebecca E.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.

2017-01-01

Background Impairment in activities of daily living is a major burden to both patients and caregivers. Mild impairment in instrumental activities of daily living is often seen at the stage of mild cognitive impairment. The field of Alzheimer’s disease is moving toward earlier diagnosis and intervention and more sensitive and ecologically valid assessments of instrumental or complex activities of daily living are needed. The Harvard Automated Phone Task, a novel performance-based activities of daily living instrument, has the potential to fill this gap. Objective To further validate the Harvard Automated Phone Task by assessing its longitudinal relationship to global cognition and specific cognitive domains in clinically normal elderly and individuals with mild cognitive impairment. Design In a longitudinal study, the Harvard Automated Phone Task was associated with cognitive measures using mixed effects models. The Harvard Automated Phone Task’s ability to discriminate across diagnostic groups at baseline was also assessed. Setting Academic clinical research center. Participants Two hundred and seven participants (45 young normal, 141 clinically normal elderly, and 21 mild cognitive impairment) were recruited from the community and the memory disorders clinics at Brigham and Women’s Hospital and Massachusetts General Hospital. Measurements Participants performed the three tasks of the Harvard Automated Phone Task, which consist of navigating an interactive voice response system to refill a prescription (APT-Script), select a new primary care physician (APT-PCP), and make a bank account transfer and payment (APT-Bank). The 3 tasks were scored based on time, errors, repetitions, and correct completion of the task. The primary outcome measure used for each of the tasks was total time adjusted for correct completion. Results The Harvard Automated Phone Task discriminated well between young normal, clinically normal elderly, and mild cognitive impairment participants (APT-Script: p<0.001; APT-PCP: p<0.001; APT-Bank: p=0.04). Worse baseline Harvard Automated Phone Task performance or worsening Harvard Automated Phone Task performance over time tracked with overall worse performance or worsening performance over time in global cognition, processing speed, executive function, and episodic memory. Conclusions Prior cross-sectional and current longitudinal analyses have demonstrated the utility of the Harvard Automated Phone Task, a new performance-based activities of daily living instrument, in the assessment of early changes in complex activities of daily living in non-demented elderly at risk for Alzheimer’s disease. Future studies will focus on cross-validation with other sensitive activities of daily living tests and Alzheimer’s disease biomarkers. PMID:29124043

Lower-normal TSH is associated with better metabolic risk factors: a cross-sectional study on spanish men

USDA-ARS?s Scientific Manuscript database

Background and aims: Subclinical thyroid conditions, defined by normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels, may be associated with cardiovascular and metabolic risk. More recently, TSH levels within the normal range have been suggested to be associated with metabolic ...

Rapid degradation of dominant-negative Rab27 proteins in vivo precludes their use in transgenic mouse models

PubMed Central

Ramalho, José S; Anders, Ross; Jaissle, Gesine B; Seeliger, Mathias W; Huxley, Clare; Seabra, Miguel C

2002-01-01

Background Transgenic mice have proven to be a powerful system to study normal and pathological gene functions. Here we describe an attempt to generate a transgenic mouse model for choroideremia (CHM), a slow-onset X-linked retinal degeneration caused by mutations in the Rab Escort Protein-1 (REP1) gene. REP1 is part of the Rab geranylgeranylation machinery, a modification that is essential for Rab function in membrane traffic. The loss of REP1 in CHM patients may trigger retinal degeneration through its effects on Rab proteins. We have previously reported that Rab27a is the Rab most affected in CHM lymphoblasts and hypothesised that the selective dysfunction of Rab27a (and possibly a few other Rab GTPases) plays an essential role in the retinal degenerative process. Results To investigate this hypothesis, we generated several lines of dominant-negative, constitutively-active and wild-type Rab27a (and Rab27b) transgenic mice whose expression was driven either by the pigment cell-specific tyrosinase promoter or the ubiquitous β-actin promoter. High levels of mRNA and protein were observed in transgenic lines expressing wild-type or constitutively active Rab27a and Rab27b. However, only modest levels of transgenic protein were expressed. Pulse-chase experiments suggest that the dominant-negative proteins, but not the constitutively-active or wild type proteins, are rapidly degraded. Consistently, no significant phenotype was observed in our transgenic lines. Coat-colour was normal, indicating normal Rab27a activity. Retinal function as determined by fundoscopy, angiography, electroretinography and histology was also normal. Conclusions We suggest that the instability of the dominant-negative mutant Rab27 proteins in vivo precludes the use of this approach to generate mouse models of disease caused by Rab27 GTPases. PMID:12401133

The effect of Bcr-Abl protein tyrosine kinase on maturation and proliferation of primitive haematopoietic cells.

PubMed Central

Buckle, A. M.; Mottram, R.; Pierce, A.; Lucas, G. S.; Russell, N.; Miyan, J. A.; Whetton, A. D.

2000-01-01

BACKGROUND: Chronic Myeloid Leukaemia (CML) is characterised by the chromosomal translocation resulting in expression of the Bcr-Abl protein tyrosine kinase (PTK) in early stem cells and their progeny. However the precise nature of Bcr-Abl effects in primitive CML stem cells remains a matter of active debate. MATERIALS AND METHODS: Extremely primitive Bcr-Abl fusion positive cells were purified from patients with CML using multiparameter flow cytometric analysis of CD34, Thy, and lineage marker (Lin) expression, plus rhodamine-123 (Rh-123) brightness. Progenitor cells of increasing maturity were examined for cycling status by flow cytometry and their proliferative status directly correlated with cell phenotype. The activation status of a key transcription factor, signal transducers and activators of transcription (STAT-5), was also analyzed by immunocytochemistry. RESULTS: The most primitive stem cells currently defined (CD34+Lin-Thy+ Rh-1231o) were present as a lower proportion of the stem cell compartment (CD34+Lin-) of CML patients at presentation than of normal individuals (2.3% +/- 0.4 compared with 5.1% +/- 0.6 respectively). Conversely there was a significantly higher proportion of the more mature cells (CD34+Lin-Thy-Rh-123 hi) in CML patients than in normal individuals (79.3 +/- 1.8 compared with 70.9 +/- 3.3). No primitive subpopulation of CML CD34+Lin- cells was cycling to a significantly greater degree than cells from normal donors, in fact, late progenitor cells (CD34+Lin+) were cycling significantly less in CML samples than normal samples. STAT5, however, was observed to be activated in CML cells. CONCLUSIONS: We conclude that no subpopulation of CML stem cells displays significantly increased cell cycling. Thus, increased cycling cannot be a direct consequence of Bcr-Abl PTK acquisition in highly enriched stem cells from patients with CML. In vivo CML need not be considered a disease of unbridled stem cell proliferation, but a subtle defect in the balance between self renewal and maturation. PMID:11126203

Prosocial Behaviors during School Activities among Child Survivors after the 2011 Earthquake and Tsunami in Japan: A Retrospective Observational Study

PubMed Central

Usami, Masahide; Iwadare, Yoshitaka; Watanabe, Kyota; Kodaira, Masaki; Ushijima, Hirokage; Tanaka, Tetsuya; Harada, Maiko; Tanaka, Hiromi; Sasaki, Yoshinori; Okamoto, Seiko; Sekine, Keisuke; Saito, Kazuhiko

2014-01-01

Background The 2011 Japan massive tsunami traumatized many children. The aim of this study was to assess changes in strengths and difficulties experienced in home and school by among surviving children after the 2011 tsunami, in comparison with published normal Japanese data. Methods In November 2012 (20 months after the disaster) and September 2013 (30 months after the disaster), the Strengths and Difficulties Questionnaire (SDQ), a questionnaire on children's strengths and difficulties in home and school activities, were distributed to 12,193 and 11,819 children, respectively. An effective response of children 20 months and 30 month after the disaster was obtained in 10,597 children (86.9%), and 10,812 children (91.4%), respectively. The SDQ scores evaluated by parents and teachers were compared with published normal Japanese SDQ scores. Results The SDQ scores (emotional problems, conduct problems, hyperactivity/inattention, peer relationship problems, and total difficulty score) evaluated by parents of children in the 4th to 9th grade who were evaluated after 30 and 20 months were significantly high compared with the published normal data of children without traumatic experiences (all P<0.001). The SDQ scores (prosocial behavior) evaluated by teachers of children in the 4th to 9th grade who were evaluated after 30 and 20 months were significantly low compared with the published normal data of children without traumatic experiences (all P<0.001). Conclusions This study showed that the experience of the disaster affected those children with prosocial behaviors towards teachers and friends at school. However, no significant changes (in their prosocial attitude) had been seen at home, where they continued to keep their respect and caring feelings for parents. These results indicate that for accurate diagnosis, clinicians should not only evaluate these children's daily activities at home but also try to objectively assess their daily activities at school. PMID:25415450

Effect of vitamin E (Tri E®) on antioxidant enzymes and DNA damage in rats following eight weeks exercise

PubMed Central

2011-01-01

Background Exercise is beneficial to health, but during exercise the body generates reactive oxygen species (ROS) which are known to result in oxidative stress. The present study analysed the effects of vitamin E (Tri E®) on antioxidant enzymes; superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (Cat) activity and DNA damage in rats undergoing eight weeks exercise. Methods Twenty four Sprague-Dawley rats (weighing 320-370 gm) were divided into four groups; a control group of sedentary rats which were given a normal diet, second group of sedentary rats with oral supplementation of 30 mg/kg/d of Tri E®, third group comprised of exercised rats on a normal diet, and the fourth group of exercised rats with oral supplementation of 30 mg/kg/d of Tri E®. The exercising rats were trained on a treadmill for 30 minutes per day for 8 weeks. Blood samples were taken before and after 8 weeks of the study to determine SOD, GPx, Cat activities and DNA damage. Results SOD activity decreased significantly in all the groups compared to baseline, however both exercised groups showed significant reduction in SOD activity as compared to the sedentary groups. Sedentary control groups showed significantly higher GPx and Cat activity compared to baseline and exercised groups. The supplemented groups, both exercised and non exercised groups, showed significant decrease in Cat activity as compared to their control groups with normal diet. DNA damage was significantly higher in exercising rats as compared to sedentary control. However in exercising groups, the DNA damage in supplemented group is significantly lower as compared to the non-supplemented group. Conclusions In conclusion, antioxidant enzymes activity were generally reduced in rats supplemented with Tri E® probably due to its synergistic anti-oxidative defence, as evidenced by the decrease in DNA damage in Tri E® supplemented exercise group. PMID:21513540

Ventral frontal satiation-mediated responses to food aromas in obese and normal-weight women123

PubMed Central

Eiler, William JA; Dzemidzic, Mario; Case, K Rose; Armstrong, Cheryl LH; Mattes, Richard D; Cyders, Melissa A; Considine, Robert V; Kareken, David A

2014-01-01

Background: Sensory properties of foods promote and guide consumption in hunger states, whereas satiation should dampen the sensory activation of ingestive behaviors. Such activation may be disordered in obese individuals. Objective: Using functional magnetic resonance imaging (fMRI), we studied regional brain responses to food odor stimulation in the sated state in obese and normal-weight individuals targeting ventral frontal regions known to be involved in coding for stimulus reward value. Design: Forty-eight women (25 normal weight; 23 obese) participated in a 2-day (fed compared with fasting) fMRI study while smelling odors of 2 foods and an inedible, nonfood object. Analyses were conducted to permit an examination of both general and sensory-specific satiation (satiation effects specific to a given food). Results: Normal-weight subjects showed significant blood oxygen level–dependent responses in the ventromedial prefrontal cortex (vmPFC) to food aromas compared with responses induced by the odor of an inedible object. Normal-weight subjects also showed general (but not sensory-specific) satiation effects in both the vmPFC and orbitofrontal cortex. Obese subjects showed no differential response to the aromas of food and the inedible object when fasting. Within- and between-group differences in satiation were driven largely by changes in the response to the odor of the inedible stimulus. Responses to food aromas in the obese correlated with trait negative urgency, the tendency toward negative affect-provoked impulsivity. Conclusions: Ventral frontal signaling of reward value may be disordered in obesity, with negative urgency heightening responses to food aromas. The observed nature of responses to food and nonfood stimuli suggests that future research should independently quantify each to fully understand brain reward signaling in obesity. This trial was registered at clinicaltrials.gov as NCT02041039. PMID:24695888

A NOVEL MUTATION IN THE HCN4 GENE CAUSES SYMPTOMATIC SINUS BRADYCARDIA IN MOROCCAN JEWS

PubMed Central

Laish-Farkash, Avishag; Brass, Dovrat; Marek-Yagel, Dina; Pras, Elon; Dascal, Nathan; Antzelevitch, Charles; Nof, Eyal; Reznik, Haya; Eldar, Michael; Glikson, Michael; Luria, David

2010-01-01

Objectives To conduct a clinical, genetic and functional analysis of three unrelated families with familial sinus bradycardia (FSB). Background Mutations in the hyperpolarization-activated nucleotide-gated channel (HCN4) are known to be associated with FSB. Methods and Results Three males of Moroccan Jewish descent were hospitalized: one survived an out-of-hospital cardiac arrest and 2 presented with weakness and presyncopal events. All 3 had significant sinus bradycardia, also found in other first-degree relatives, with a segregation suggesting autosomal-dominant inheritance. All had normal response to exercise and normal heart structure. Sequencing of the HCN4 gene in all patients revealed a C to T transition at nucleotide position 1454, which resulted in an alanine to valine change (A485V) in the ion channel pore found in most of their bradycardiac relatives, but not in 150 controls. Functional expression of the mutated ion channel in Xenopus oocytes and in human embryonic kidney 293 cells revealed profoundly reduced function and synthesis of the mutant channel compared to wild-type. Conclusions We describe a new mutation in the HCN4 gene causing symptomatic FSB in 3 unrelated individuals of similar ethnic background that may indicate unexplained FSB in this ethnic group. This profound functional defect is consistent with the symptomatic phenotype. PMID:20662977

Myb proteins: angels and demons in normal and transformed cells

PubMed Central

Zhou, Ye; Ness, Scott A.

2013-01-01

A key regulator of proliferation, differentiation and cell fate, the c-Myb transcription factor regulates the expression of hundreds of genes and is in turn regulated by numerous pathways and protein interactions. However, the most unique feature of c-Myb is that it can be converted into an oncogenic transforming protein through a few mutations that completely change its activity and specificity. The c-Myb protein is a myriad of interactions and activities rolled up in a protein that controls proliferation and differentiation in many different cell types. Here we discuss the background and recent progress that have led to a better understanding of this complex protein, and outline the questions that have yet to be answered. PMID:21196221

Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis

PubMed Central

2012-01-01

Background Plasminogen activator inhibitor 1 (PAI-1) overexpression is an important prognostic and predictive biomarker in human breast cancer. SERBP1, a protein that is supposed to regulate the stability of PAI-1 mRNA, may play a role in gynaecological cancers as well, since upregulation of SERBP1 was described in ovarian cancer recently. This is the first study to present a systematic characterisation of SERBP1 expression in human breast cancer and normal breast tissue at both the mRNA and the protein level. Methods Using semiquantitative realtime PCR we analysed SERBP1 expression in different normal human tissues (n = 25), and in matched pairs of normal (n = 7) and cancerous breast tissues (n = 7). SERBP1 protein expression was analysed in two independent cohorts on tissue microarrays (TMAs), an initial evaluation set, consisting of 193 breast carcinomas and 48 normal breast tissues, and a second large validation set, consisting of 605 breast carcinomas. In addition, a collection of benign (n = 2) and malignant (n = 6) mammary cell lines as well as breast carcinoma lysates (n = 16) were investigated for SERBP1 expression by Western blot analysis. Furthermore, applying non-radioisotopic in situ hybridisation a subset of normal (n = 10) and cancerous (n = 10) breast tissue specimens from the initial TMA were analysed for SERBP1 mRNA expression. Results SERBP1 is not differentially expressed in breast carcinoma compared to normal breast tissue, both at the RNA and protein level. However, recurrence-free survival analysis showed a significant correlation (P = 0.008) between abundant SERBP1 expression in breast carcinoma and favourable prognosis. Interestingly, overall survival analysis also displayed a tendency (P = 0.09) towards favourable prognosis when SERBP1 was overexpressed in breast cancer. Conclusions The RNA-binding protein SERBP1 is abundantly expressed in human breast cancer and may represent a novel breast tumour marker with prognostic significance. Its potential involvement in the plasminogen activator protease cascade warrants further investigation. PMID:23236990

Locations of Joint Physical Activity in Parent-Child Pairs Based on Accelerometer and GPS Monitoring

PubMed Central

Dunton, Genevieve Fridlund; Liao, Yue; Almanza, Estela; Jerrett, Micheal; Spruijt-Metz, Donna; Pentz, Mary Ann

2012-01-01

Background Parental factors may play an important role in influencing children’s physical activity levels. Purpose This cross-sectional study sought to describe the locations of joint physical activity among parents and children. Methods Parent-child pairs (N = 291) wore an Actigraph GT2M accelerometer and GlobalSat BT-335 Global Positioning Systems (GPS) device over the same 7-day period. Children were ages 8–14 years. Joint behavior was defined by a linear separation distance of less than 50m between parent and child. Land use classifications were assigned to GPS data points. Results Joint physical activity was spread across residential locations (35%), and commercial venues (24%), and open spaces/parks (20%). Obese children and parents performed less joint physical activity in open spaces/parks than under/normal weight children and parents (p’s < .01). Conclusions Understanding where joint parent-child physical activity naturally occurs may inform location-based interventions to promote these behaviors. PMID:23011914

New direct measurement of the 10B(p,α)7Be reaction with the activation technique

NASA Astrophysics Data System (ADS)

Depalo, Rosanna; Caciolli, Antonio; Broggini, Carlo; La Cognata, Marco; Lamia, Livio; Menegazzo, Roberto; Mou, Liliana; Puglia, Sebastiana Maria Regina; Rigato, Valentino; Romano, Stefano; Alvarez, Carlos Rossi; Sergi, Maria Letizia; Spitaleri, Claudio; Tumino, Aurora

2018-01-01

Boron plays an important role in astrophysics and, together with lithium and beryllium, is a probe of stellar structure during the pre-main sequence and main-sequence phases. In this context, the 10B(p,α)7 Be reaction is of particular interest. The literature data show discrepancies in the energy range between 100 keV and 2 MeV. This also poses a normalization problem for indirect data obtained with the Trojan Horse Method. A new measurement of the 10B(p,α)7 Be reaction cross section was performed at Legnaro National Laboratories (LNL). At LNL, the cross section was determined with the activation technique by measuring the activated samples at a low-background counting facility. The analysis of that experiment is now complete and the results are here presented.

Diurnal variations of ELF transients and background noise in the Schumann resonance band

NASA Astrophysics Data System (ADS)

Greenberg, Eran; Price, Colin

2007-02-01

Schumann resonances (SR) are resonant electromagnetic waves in the Earth-ionosphere cavity, induced primarily by lightning discharges, with a fundamental frequency of about 8 Hz and higher-order modes separated by approximately 6 Hz. The SR are made up of the background signal resulting from global lightning activity and extremely low frequency (ELF) transients resulting from particularly intense lightning discharges somewhere on the planet. Since transients within the Earth-ionosphere cavity due to lightning propagate globally in the ELF range, we can monitor and study global ELF transients from a single station. Data from our Negev Desert (Israel) ELF site are collected using two horizontal magnetic induction coils and a vertical electric field ball antenna, monitored in the 5-40 Hz range with a sampling frequency of 250 Hz. In this paper we present statistics related to the probability distribution of ELF transients and background noise in the time domain and its temporal variations during the day. Our results show that the ELF signal in the time domain follows the normal distribution very well. The σ parameter exhibits three peaks at 0800, 1400, and 2000 UT, which are related to the three main global lightning activity centers in Asia, Africa, and America, respectively. Furthermore, the occurrence of intense ELF events obeys the Poisson distribution, with such intense events occurring every ~10 s, depending on the time of the day. We found that the diurnal changes of the σ parameter are several percent of the mean, while for the number of intense events per minute, the diurnal changes are tens of percent about the mean. We also present the diurnal changes of the SR intensities in the frequency domain as observed at our station. To better understand the diurnal variability of the observations, we simulated the measured ELF background noise using space observations as input, as detected by the Optical Transient Detector (OTD). The most active center which is reflected from both ELF measurements and OTD observations is in Africa. However, the second most active center on the basis of ELF measurements appears to be Asia, while OTD observations show that the American center is more active than the Asian center. These differences are discussed. This paper contributes to our understanding of the origin of the SR by comparing different lightning data sets: background electromagnetic radiation and optical emission observed from space.

Tumour growth, phagocytic activity and antibody response in corynebacterium parvum-treated mice

PubMed Central

Woodruff, M. F. A.; McBride, W. H.; Dunbar, Noreen

1974-01-01

Serum from both normal and T cell-deprived female adult CBA mice shows a background titre of antibody to Corynebacterium parvum of about 2–4 log2 units by a latex agglutination test. Intraperitoneal injection of C. parvum causes a marked rise in titre which reaches its peak after about a month, and a second injection at that time evokes a further response. Treatment with mercaptoethanol reduces the background titre, and also the titre 1–3 weeks after immunization by 1–2 log units. Subcutaneous injection of C. parvum on the other hand evokes little or no antibody response. Both the antitumour effect of C. parvum, and its effect on clearance of colloidal carbon from the blood stream, can occur in the presence of high levels of antibody directed against the organism. Theoretical and possible therapeutic implications of these findings are discussed. PMID:4549691

Effect of Energy Equalization on the Intelligibility of Speech in Fluctuating Background Interference for Listeners With Hearing Impairment

PubMed Central

D’Aquila, Laura A.; Desloge, Joseph G.; Braida, Louis D.

2017-01-01

The masking release (MR; i.e., better speech recognition in fluctuating compared with continuous noise backgrounds) that is evident for listeners with normal hearing (NH) is generally reduced or absent for listeners with sensorineural hearing impairment (HI). In this study, a real-time signal-processing technique was developed to improve MR in listeners with HI and offer insight into the mechanisms influencing the size of MR. This technique compares short-term and long-term estimates of energy, increases the level of short-term segments whose energy is below the average energy, and normalizes the overall energy of the processed signal to be equivalent to that of the original long-term estimate. This signal-processing algorithm was used to create two types of energy-equalized (EEQ) signals: EEQ1, which operated on the wideband speech plus noise signal, and EEQ4, which operated independently on each of four bands with equal logarithmic width. Consonant identification was tested in backgrounds of continuous and various types of fluctuating speech-shaped Gaussian noise including those with both regularly and irregularly spaced temporal fluctuations. Listeners with HI achieved similar scores for EEQ and the original (unprocessed) stimuli in continuous-noise backgrounds, while superior performance was obtained for the EEQ signals in fluctuating background noises that had regular temporal gaps but not for those with irregularly spaced fluctuations. Thus, in noise backgrounds with regularly spaced temporal fluctuations, the energy-normalized signals led to larger values of MR and higher intelligibility than obtained with unprocessed signals. PMID:28602128

A comparative study on long-term evoked auditory and visual potential responses between Schizophrenic patients and normal subjects

PubMed Central

2011-01-01

Background The electrical signals measuring method is recommended to examine the relationship between neuronal activities and measure with the event related potentials (ERPs) during an auditory and a visual oddball paradigm between schizophrenic patients and normal subjects. The aim of this study is to discriminate the activation changes of different stimulations evoked by auditory and visual ERPs between schizophrenic patients and normal subjects. Methods Forty-three schizophrenic patients were selected as experimental group patients, and 40 healthy subjects with no medical history of any kind of psychiatric diseases, neurological diseases, or drug abuse, were recruited as a control group. Auditory and visual ERPs were studied with an oddball paradigm. All the data were analyzed by SPSS statistical software version 10.0. Results In the comparative study of auditory and visual ERPs between the schizophrenic and healthy patients, P300 amplitude at Fz, Cz, and Pz and N100, N200, and P200 latencies at Fz, Cz, and Pz were shown significantly different. The cognitive processing reflected by the auditory and the visual P300 latency to rare target stimuli was probably an indicator of the cognitive function in schizophrenic patients. Conclusions This study shows the methodology of application of auditory and visual oddball paradigm identifies task-relevant sources of activity and allows separation of regions that have different response properties. Our study indicates that there may be slowness of automatic cognitive processing and controlled cognitive processing of visual ERPs compared to auditory ERPs in schizophrenic patients. The activation changes of visual evoked potentials are more regionally specific than auditory evoked potentials. PMID:21542917

Differences in the melanosome distribution within the epidermal melanin units and its association with the impairing background of leukoderma in vitiligo and halo nevi: a retrospective study.

PubMed

Xiong, Xi-Xi; Ding, Gao-Zhong; Zhao, Wen-E; Li, Xue; Ling, Yu-Ting; Sun, Li; Gong, Qing-Li; Lu, Yan

2017-07-01

Skin color is determined by the number of melanin granules produced by melanocytes that are transferred to keratinocytes. Melanin synthesis and the distribution of melanosomes to keratinocytes within the epidermal melanin unit (EMU) within the skin of vitiligo patients have been poorly studied. The ultrastructure and distribution of melanosomes in melanocytes and surrounding keratinocytes in perilesional vitiligo and normal skin were investigated using transmission electron microscopy (TEM). Furthermore, we performed a quantitative analysis of melanosome distribution within the EMUs with scatter plot. Melanosome count within keratinocytes increased significantly compared with melanocytes in perilesional stable vitiligo (P < 0.001), perilesional halo nevi (P < 0.01) and the controls (P < 0.01), but not in perilesional active vitiligo. Furthermore, melanosome counts within melanocytes and their surrounding keratinocytes in perilesional active vitiligo skin decreased significantly compared with the other groups. In addition, taking the means-standard error of melanosome count within melanocytes and keratinocytes in healthy controls as a normal lower limit, EMUs were graded into 3 stages (I-III). Perilesional active vitiligo presented a significantly different constitution in stages compared to other groups (P < 0.001). The distribution and constitution of melanosomes were normal in halo nevi. Impaired melanin synthesis and melanosome transfer are involved in the pathogenesis of vitiligo. Active vitiligo varies in stages and in stage II, EMUs are slightly impaired, but can be resuscitated, providing a golden opportunity with the potential to achieve desired repigmentation with an appropriate therapeutic choice. Adverse milieu may also contribute to the low melanosome count in keratinocytes.

An Exploratory Study of Autonomic Function Investigations in Hemophiliacs on Homoeopathy Medications Using Impedance Plethysmography

PubMed Central

Kundu, Tapas K.; Barde, Pradip B.; Jindal, Ghanshyam D.; Motiwala, Farooq F.

2017-01-01

Background. Status of autonomic homoeostasis in hemostasic disturbances due to hemophilia needs to be studied. Objectives. To compare autonomic nervous system markers measured by heart rate variability (HRV) and blood flow variability (BFV) in hemophiliacs and healthy age-matched control population using medical analyzer system. Design. Cross-sectional study. Settings. Motiwala Homoeopathy Medical College, and Hemophilia Clinics, Nashik. Subjects. Eighty subjects. Interventions. Nil. Outcome Measures. Autonomic function markers for HRV and BFV. Results. Among 80 subjects, BFV time domain measure, root mean square of successive NN (normal-to-normal) interval differences (RMSSD), was significantly higher among hemophiliacs than nonhemophiliacs. Frequency domain analysis parameter, low frequency for both HRV and BFV was significantly higher among hemophiliacs as compared with nonhemophiliacs. Conclusions. Hemophiliacs were shown to have higher autonomic activity as compared with healthy controls. Homoeopathic medicines used as an adjunct was associated with decrease in parasympathetic modulations. PMID:28719973

Speech Sound Processing Deficits and Training-Induced Neural Plasticity in Rats with Dyslexia Gene Knockdown

PubMed Central

Centanni, Tracy M.; Chen, Fuyi; Booker, Anne M.; Engineer, Crystal T.; Sloan, Andrew M.; Rennaker, Robert L.; LoTurco, Joseph J.; Kilgard, Michael P.

2014-01-01

In utero RNAi of the dyslexia-associated gene Kiaa0319 in rats (KIA-) degrades cortical responses to speech sounds and increases trial-by-trial variability in onset latency. We tested the hypothesis that KIA- rats would be impaired at speech sound discrimination. KIA- rats needed twice as much training in quiet conditions to perform at control levels and remained impaired at several speech tasks. Focused training using truncated speech sounds was able to normalize speech discrimination in quiet and background noise conditions. Training also normalized trial-by-trial neural variability and temporal phase locking. Cortical activity from speech trained KIA- rats was sufficient to accurately discriminate between similar consonant sounds. These results provide the first direct evidence that assumed reduced expression of the dyslexia-associated gene KIAA0319 can cause phoneme processing impairments similar to those seen in dyslexia and that intensive behavioral therapy can eliminate these impairments. PMID:24871331

MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women.

PubMed

Diamanti-Kandarakis, Evanthia; Papalou, Olga; Kandaraki, Eleni A; Kassi, Georgia

2017-02-01

Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders. © 2017 European Society of Endocrinology.

Cytologic features of the normal pineal gland on squash preparations.

PubMed

Murro, Diana; Alsadi, Alaa; Nag, Sukriti; Arvanitis, Leonidas; Gattuso, Paolo

2014-11-01

As primary pineal lesions are extremely rare, many surgical pathologists are unfamiliar with normal pineal cytologic features. We describe cytologic features of the normal pineal gland in patients of varying ages and identify common diagnostic pitfalls. We performed a retrospective review of pineal gland biopsies performed at our institution, where approximately 30,000 surgical specimens are accessioned yearly, for the last 23 years. Only two pineal gland biopsies were found. Although both cases were initially diagnosed as low-grade gliomas on frozen section, the final diagnosis was benign pineal tissue based on light microscopy and immunohistochemistry results. Additionally, we performed squash preparations of five normal pineal gland autopsy specimens with Papanicolaou and Diff-Quik® (Dade Behring, Newark, DE) stains. Infant preparations were highly cellular smears composed of numerous, uniform, single cells with indistinct cytoplasm, small round-to-oval nuclei, fine chromatin, and absent nucleoli and calcifications. The vague microfollicular pattern mimicked a pineocytoma and the fine fibrillary background mimicked a glial neoplasm. Young adult smears were similar; however, microcalcifications were present with fewer background single cells. Older patients had much less cellular smears composed of small clusters of cells with fusiform-to-spindle nuclei, a fine chromatin pattern, and indistinct cytoplasmic borders. There were fewer background single cells and more microcalcifications. The cytologic features of the native pineal gland vary with age. Normal pineal tissue can be confused with a pineocytoma or low-grade glioma. Familiarity with normal pineal gland cytological features will help to avoid a potential misdiagnosis. © 2014 Wiley Periodicals, Inc.

Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis

PubMed Central

Altman, Raul; Scazziota, Alejandra Silvia; Herrera, Maria de Lourdes; Gonzalez, Claudio

2006-01-01

Background Platelet activation is crucial in normal hemostasis. Using a clotting system free of external tissue factor, we investigated whether activated Factor VII in combination with platelet agonists increased thrombin generation (TG) in vitro. Methods and results TG was quantified by time parameters: lag time (LT) and time to peak (TTP), and by amount of TG: peak of TG (PTG) and area under thrombin formation curve after 35 minutes (AUC→35min) in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT) technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA), ADP, and collagen (Col). In addition, the effects of recombinant activated FVII (rFVIIa) alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p < 0.05) and PTG and AUC→35min were significantly increased (p < 0.05) in platelet rich plasma activated with AA, ADP, Col, and rFVIIa compared to non-activated platelet rich plasma from normal subjects (p = 0.01). Furthermore platelet rich plasma activated by the combined effects of rFVIIa plus AA, ADP or Col had significantly reduced LT and TTP and increased AUC→35min (but not PTG) when compared to platelet rich plasma activated with agonists in the absence of rFVIIa. Conclusion Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis. PMID:16630353

Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties

PubMed Central

Godlewska, Marlena; Arczewska, Katarzyna D.; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław

2017-01-01

Background Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. Methods In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. Results We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Conclusions Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism. PMID:28575127

Active Sonic Hedgehog Signaling between Androgen Independent Human Prostate Cancer Cells and Normal/Benign but Not Cancer-Associated Prostate Stromal Cells

PubMed Central

Shigemura, Katsumi; Huang, Wen-Chin; Li, Xiangyan; Zhau, Haiyen E.; Zhu, Guodong; Gotoh, Akinobu; Fujisawa, Masato; Xie, Jingwu; Marshall, Fray F.; Chung, Leland W. K.

2012-01-01

BACKGROUND Sonic hedgehog (Shh) signaling plays a pivotal role in stromal-epithelial interaction during normal development but its role in tumor-stromal interaction during carcinogenic progression is less well defined. Since hormone refractory prostate cancer with bone metastasis is difficult to treat, it is crucial to investigate how androgen independent (AI) human prostate cancer cells communicate with their associated stroma. METHODS Shh and its target transcription factor, Gli1 mRNA, were assessed by RT-PCR and/or quantitative RT-PCR in co-cultured cell recombinants comprised of AI C4-2 either with NPF (prostate fibroblasts from normal/benign prostate gland) or CPF cancer-associated stromal fibroblasts) under Shh/cyclopamine (a hedgehog signaling inhibitor) treatment. Human bone marrow stromal (HS27A) cells were used as controls. In vivo investigation was performed by checking serum PSA and immunohistochemical staining for the apoptosis-associated M30 gene in mice bearing chimeric C4-2/NPF tumors. RESULTS CONCLUSIONS Based on co-culture and chimeric tumor models, active Shh-mediated signaling was demonstrated between AI prostate cancer and NPF in a paracrine- and tumor progression-dependent manner. Our study suggests that drugs like cyclopamine that interfere with Shh signaling could be beneficial in preventing AI progression in prostate cancer cells. PMID:21520153

Percutaneous release of the plantar fascia. New surgical procedure

PubMed Central

Oliva, Francesco; Piccirilli, Eleonora; Tarantino, Umberto; Maffulli, Nicola

2017-01-01

Summary Background Plantar fasciopathy presents with pain at the plantar and medial aspect of the heel. If chronic, it can negatively impact on quality of life. Plantar fasciopathy is not always self-limiting, and can be debilitating. Methods Surgical management involves different procedures. We describe a percutaneous plantar fascia release. A minimally invasive access to the plantar tuberosity of the calcaneus is performed, and a small scalpel blade is used to release the fascia. Conclusion With this procedure, skin healing problems, nerve injuries, infection and prolonged recovery time are minimised, allowing early return to normal activities. Level of Evidence V. PMID:29264346

Cardiac Uptake of Minocycline and Mechanisms for In Vivo Cardioprotection

PubMed Central

Romero-Perez, Diego; Fricovsky, Eduardo; Yamasaki, Katrina Go; Griffin, Michael; Barraza-Hidalgo, Maraliz; Dillmann, Wolfgang; Villarreal, Francisco

2008-01-01

Objectives The ability of minocycline to be transported into cardiac cells, concentrate in normal and ischemic myocardium and act as in vivo cardioprotector was examined. We also determined minocycline's capacity to act as a reducer of myocardial oxidative stress and matrix metalloproteinase (MMP) activity. Background The identification of compounds with the potential to reduce myocardial ischemic injury is of great interest. Tetracyclines (TTCs) are antibiotics with pleiotropic cytoprotective properties that accumulate in normal and diseased tissues. Minocycline is highly lipophilic and has shown promise as a possible cardioprotector. However, minocycline's potential as an in vivo cardioprotector as well as the means by which this action is attained are not well understood. Methods Rats were subjected to 45 min of ischemia and 48 h of reperfusion. Animals were treated 48 h before and 48 h after thoracotomy with either vehicle or 50 mg/kg/day minocycline. Tissue samples were used for biochemical assays and cultured cardiac cells for minocycline uptake experiments. Results Minocycline significantly reduced infarct size (∼33%), tissue MMP-9 activity and oxidative stress. Minocycline was concentrated ∼24-fold in normal (0.5 mM) and ∼50-fold in ischemic regions (1.1 mM) vs. blood. Neonatal rat cardiac fibroblasts, myocytes and adult fibroblasts demonstrate a time- and temperature-dependent uptake of minocycline to levels that approximate those of normal myocardium. Conclusions Given the high intracellular levels observed and results from the assessment of in vitro antioxidant and MMP inhibitor capacities, it is likely that minocycline acts to limit myocardial ischemic injury via mass action effects. PMID:18848143

Constrained sampling experiments reveal principles of detection in natural scenes.

PubMed

Sebastian, Stephen; Abrams, Jared; Geisler, Wilson S

2017-07-11

A fundamental everyday visual task is to detect target objects within a background scene. Using relatively simple stimuli, vision science has identified several major factors that affect detection thresholds, including the luminance of the background, the contrast of the background, the spatial similarity of the background to the target, and uncertainty due to random variations in the properties of the background and in the amplitude of the target. Here we use an experimental approach based on constrained sampling from multidimensional histograms of natural stimuli, together with a theoretical analysis based on signal detection theory, to discover how these factors affect detection in natural scenes. We sorted a large collection of natural image backgrounds into multidimensional histograms, where each bin corresponds to a particular luminance, contrast, and similarity. Detection thresholds were measured for a subset of bins spanning the space, where a natural background was randomly sampled from a bin on each trial. In low-uncertainty conditions, both the background bin and the amplitude of the target were fixed, and, in high-uncertainty conditions, they varied randomly on each trial. We found that thresholds increase approximately linearly along all three dimensions and that detection accuracy is unaffected by background bin and target amplitude uncertainty. The results are predicted from first principles by a normalized matched-template detector, where the dynamic normalizing gain factor follows directly from the statistical properties of the natural backgrounds. The results provide an explanation for classic laws of psychophysics and their underlying neural mechanisms.

Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor activity in mice

PubMed Central

Ye, Xiangcang; Han, Sang Jun; Tsai, Sophia Y.; DeMayo, Francesco J.; Xu, Jianming; Tsai, Ming-Jer; O'Malley, Bert W.

2005-01-01

Genetic disruption of the steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF)2/SRC-2 in mouse resulted in distinctive mutant phenotypes. To quantify their roles in the function of androgen receptor (AR) transcriptional activity in vivo, we generated a unique transgenic AR-reporter mouse and analyzed the cell-specific contributions of SRC-1 and TIF2 to the activity of AR in mouse testis. Transgenic AR-luciferase and transgenic AR-lacZ mice harbor a recombinant mouse AR gene, ARGAL4DBD, which is functionally coupled with a upstream activation sequence-mediated reporter gene (AR activity indicator). After characterization of these mice in terms of AR function, we further derived bigenic mice by crossing AR activity indicator mice with the SRC-1-/- or TIF2+/- mutant mice. Analyses of the resultant bigenic mice by in vivo imaging and luciferase assays showed that testicular AR activity was decreased significantly in those with the TIF2+/- mutation but not in the SRC-1+/- background, suggesting that TIF2 serves as the preferential coactivator for AR in testis. Immunohistological analysis confirmed that AR and TIF2 coexist in mouse testicular Sertoli cell nuclei under normal conditions. Although SRC-1 concentrates in Sertoli cell nuclei in the absence of TIF2, nuclear SRC-1 is not able to rescue AR activity in the TIF2 mutant background. Interestingly, SRC-1 appears to negatively influence AR activity, thereby counterbalancing the TIF2-stimulated AR activity. Our results provide unique in vivo insights to the multidimensional cell-type-specific interactions between AR and coregulators. PMID:15983373

Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor activity in mice.

PubMed

Ye, Xiangcang; Han, Sang Jun; Tsai, Sophia Y; DeMayo, Francesco J; Xu, Jianming; Tsai, Ming-Jer; O'Malley, Bert W

2005-07-05

Genetic disruption of the steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF)2/SRC-2 in mouse resulted in distinctive mutant phenotypes. To quantify their roles in the function of androgen receptor (AR) transcriptional activity in vivo, we generated a unique transgenic AR-reporter mouse and analyzed the cell-specific contributions of SRC-1 and TIF2 to the activity of AR in mouse testis. Transgenic AR-luciferase and transgenic AR-lacZ mice harbor a recombinant mouse AR gene, AR(GAL4DBD), which is functionally coupled with a upstream activation sequence-mediated reporter gene (AR activity indicator). After characterization of these mice in terms of AR function, we further derived bigenic mice by crossing AR activity indicator mice with the SRC-1-/- or TIF2+/- mutant mice. Analyses of the resultant bigenic mice by in vivo imaging and luciferase assays showed that testicular AR activity was decreased significantly in those with the TIF2+/- mutation but not in the SRC-1+/- background, suggesting that TIF2 serves as the preferential coactivator for AR in testis. Immunohistological analysis confirmed that AR and TIF2 coexist in mouse testicular Sertoli cell nuclei under normal conditions. Although SRC-1 concentrates in Sertoli cell nuclei in the absence of TIF2, nuclear SRC-1 is not able to rescue AR activity in the TIF2 mutant background. Interestingly, SRC-1 appears to negatively influence AR activity, thereby counterbalancing the TIF2-stimulated AR activity. Our results provide unique in vivo insights to the multidimensional cell-type-specific interactions between AR and coregulators.

Roles of Specific Membrane Lipid Domains in EGF Receptor Activation and Cell Adhesion Molecule Stabilization in a Developing Olfactory System

PubMed Central

Gibson, Nicholas J.; Tolbert, Leslie P.; Oland, Lynne A.

2009-01-01

Background Reciprocal interactions between glial cells and olfactory receptor neurons (ORNs) cause ORN axons entering the brain to sort, to fasciculate into bundles destined for specific glomeruli, and to form stable protoglomeruli in the developing olfactory system of an experimentally advantageous animal species, the moth Manduca sexta. Epidermal growth factor receptors (EGFRs) and the cell adhesion molecules (IgCAMs) neuroglian and fasciclin II are known to be important players in these processes. Methodology/Principal Findings We report in situ and cell-culture studies that suggest a role for glycosphingolipid-rich membrane subdomains in neuron-glia interactions. Disruption of these subdomains by the use of methyl-β-cyclodextrin results in loss of EGFR activation, depletion of fasciclin II in ORN axons, and loss of neuroglian stabilization in the membrane. At the cellular level, disruption leads to aberrant ORN axon trajectories, small antennal lobes, abnormal arrays of olfactory glomerul, and loss of normal glial cell migration. Conclusions/Significance We propose that glycosphingolipid-rich membrane subdomains (possible membrane rafts or platforms) are essential for IgCAM-mediated EGFR activation and for anchoring of neuroglian to the cytoskeleton, both required for normal extension and sorting of ORN axons. PMID:19787046

Tumor Necrosis Factor Antagonism Normalizes Rapid Eye Movement Sleep in Alcohol Dependence

PubMed Central

Irwin, Michael R.; Olmstead, Richard; Valladares, Edwin M.; Breen, Elizabeth Crabb; Ehlers, Cindy L.

2009-01-01

Background In alcohol dependence, markers of inflammation are associated with increases in rapid eye movement (REM) sleep, which is thought to be a prognostic indicator of alcohol relapse. This study was undertaken to test whether blockade of biologically active tumor necrosis factor-α (TNF-α) normalizes REM sleep in alcohol-dependent adults. Methods In a randomized, placebo-controlled, double-blind, crossover trial, 18 abstinent alcohol-dependent male adults received a single dose of etanercept (25 mg) versus placebo in a counterbalanced order. Polysomnographic sleep was measured at baseline and for 3 nights after the acute dose of etanercept or placebo. Results Compared with placebo, administration of etanercept produced significant decreases in the amount and percentage of REM sleep. Decreases in REM sleep were robust and approached low levels typically found in age-comparable control subjects. Individual differences in biologically active drug as indexed by circulating levels of soluble tumor necrosis factor receptor II negatively correlated with the percentage of REM sleep. Conclusions Pharmacologic neutralization of TNF-α activity is associated with significant reductions in REM sleep in abstinent alcohol-dependent patients. These data suggest that circulating levels of TNF-α may have a physiologic role in the regulation of REM sleep in humans. PMID:19185287

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate

PubMed Central

Falcone, Mary; Cao, Wen; Bernardo, Leah; Tyndale, Rachel F; Loughead, James; Lerman, Caryn

2017-01-01

Background Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (NMR, 3′-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance, and a well validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers. Methods Sixty-nine treatment-seeking smokers (30 slow, 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once following 24 hours of smoking abstinence. Results In whole brain analysis, normal (compared to slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were even more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke. Conclusion Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy. PMID:26805583

PET-Based Confirmation of Orientation Sensitivity of TMS-Induced Cortical Activation in Humans

PubMed Central

Krieg, Todd D.; Salinas, Felipe S.; Narayana, Shalini; Fox, Peter T.; Mogul, David J.

2017-01-01

Background Currently, it is difficult to predict precise regions of cortical activation in response to transcranial magnetic stimulation (TMS). Most analytical approaches focus on applied magnetic field strength in the target region as the primary factor, placing activation on the gyral crowns. However, imaging studies support M1 targets being typically located in the sulcal banks. Objective/hypothesis To more thoroughly investigate this inconsistency, we sought to determine whether neocortical surface orientation was a critical determinant of regional activation. Methods MR images were used to construct cortical and scalp surfaces for 18 subjects. The angle (θ) between the cortical surface normal and its nearest scalp normal for ~50,000 cortical points per subject was used to quantify cortical location (i.e., gyral vs. sulcal). TMS-induced activations of primary motor cortex (M1) were compared to brain activations recorded during a finger-tapping task using concurrent positron emission tomographic (PET) imaging. Results Brain activations were primarily sulcal for both the TMS and task activations (P < 0.001 for both) compared to the overall cortical surface orientation. Also, the location of maximal blood flow in response to either TMS or finger-tapping correlated well using the cortical surface orientation angle or distance to scalp (P < 0.001 for both) as criteria for comparison between different neocortical activation modalities. Conclusion This study provides further evidence that a major factor in cortical activation using TMS is the orientation of the cortical surface with respect to the induced electric field. The results show that, despite the gyral crown of the cortex being subjected to a larger magnetic field magnitude, the sulcal bank of M1 had larger cerebral blood flow (CBF) responses during TMS. PMID:23827648

Direct evidence that genetic variation in glycerol-3-phosphate and malate dehydrogenase genes (Gpdh and Mdh1) affects adult ethanol tolerance in Drosophila melanogaster.

PubMed

Eanes, Walter F; Merritt, Thomas J S; Flowers, Jonathan M; Kumagai, Seiji; Zhu, Chen-Tseh

2009-02-01

Many studies of alcohol adaptation in Drosophila melanogaster have focused on the Adh polymorphism, yet the metabolic elimination of alcohol should involve many enzymes and pathways. Here we evaluate the effects of glycerol-3-phosphate dehydrogenase (Gpdh) and cytosolic malate dehydrogenase (Mdh1) genotype activity on adult tolerance to ethanol. We have created a set of P-element-excision-derived Gpdh, Mdh1, and Adh alleles that generate a range of activity phenotypes from full to zero activity. Comparisons of paired Gpdh genotypes possessing 10 and 60% normal activity and 66 and 100% normal activity show significant effects where higher activity increases tolerance. Mdh1 null allele homozygotes show reductions in tolerance. We use piggyBac FLP-FRT site-specific recombination to create deletions and duplications of Gpdh. Duplications show an increase of 50% in activity and an increase of adult tolerance to ethanol exposure. These studies show that the molecular polymorphism associated with GPDH activity could be maintained in natural populations by selection related to adaptation to alcohols. Finally, we examine the interactions between activity genotypes for Gpdh, Mdh1, and Adh. We find no significant interlocus interactions. Observations on Mdh1 in both Gpdh and Adh backgrounds demonstrate significant increases in ethanol tolerance with partial reductions (50%) in cytosolic MDH activity. This observation strongly suggests the operation of pyruvate-malate and, in particular, pyruvate-citrate cycling in adaptation to alcohol exposure. We propose that an understanding of the evolution of tolerance to alcohols will require a system-level approach, rather than a focus on single enzymes.

Acute effects of electromagnetic stimulation of the brain on cortical activity, cortical blood flow, blood pressure and heart rate in the cat: an evaluation of safety.

PubMed Central

Eyre, J A; Flecknell, P A; Kenyon, B R; Koh, T H; Miller, S

1990-01-01

The influence of repeated high intensity electromagnetic stimulation of the brain on cortical activity, cortical blood flow, blood pressure and heart rate has been investigated in the cat, to evaluate the safety of the method. The observations have been made in preparations under propofol anaesthesia before, during and after periods of anoxia. Electromagnetic stimulation of the brain evoked activity in descending motor pathways and was recorded by activity in the median nerve and by muscle twitches. Following repeated series of high intensity stimulation there were no systematic changes in somatosensory evoked potentials or background EEG, nor were there signs of epileptogenic activity during electromagnetic stimulation, before, during or after periods of anoxia. No systematic changes in cortical blood flow, blood pressure or heart rate were observed during electromagnetic stimulation, before or after periods of anoxia. In conclusion, no acute adverse consequences following electromagnetic stimulation in the normal and anoxic cat brain were demonstrated. PMID:2380732

Sweat Chloride as A Biomarker of CFTR Activity: Proof of Concept and Ivacaftor Clinical Trial Data

PubMed Central

Accurso, Frank J.; Van Goor, Fredrick; Zha, Jiuhong; Stone, Anne J.; Dong, Qunming; Ordonez, Claudia L.; Rowe, Steven M.; Clancy, John Paul; Konstan, Michael W.; Hoch, Heather E.; Heltshe, Sonya L.; Ramsey, Bonnie W.; Campbell, Preston W.; Ashlock, Melissa A.

2014-01-01

Background We examined data from a Phase 2 trial {NCT00457821 } of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with a G551D mutation to evaluate standardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference (NPD) to estimate CFTR activity. Methods Sweat chloride and NPD were secondary endpoints in this placebo-controlled, multicenter trial. Standardization of sweat collection, processing, and analysis was employed for the first time.. Sweat chloride and chloride ion transport (NPD) were integrated into a model of CFTR activity. Results Within-patient sweat chloride determinations showed sufficient precision to detect differences between dose-groups and assess ivacaftor treatment effects. Analysis of changes in sweat chloride and NPD demonstrated that patients treated with ivacaftor achieved CFTR activity equivalent to approximately 35%–40% of normal. Conclusions Sweat chloride is useful in multicenter trials as a biomarker of CFTR activity and to test the effect of CFTR potentiators. PMID:24660233

Comparison of Laparoscopic and Microscopic Subinguinal Varicocelectomy in terms of Postoperative Scrotal Pain

PubMed Central

Penbegül, Necmettin; Atar, Murat; Bozkurt, Yaşar; Sancaktutar, Ahmet Ali; Altunoluk, Bülent

2012-01-01

Background and Objectives: In this study, 2 different varicocelectomy methods were compared with regard to postoperative scrotal pain, length of operation, and complications. Methods: Forty varicocele patients, who visited our clinic because of infertility or scrotal pain between 2008 and 2009, were enrolled in this clinical study. Microscopic subinguinal varicocelectomy was performed on 20 patients in Group I, and laparoscopic varicocelectomy was performed on 20 patients in Group II. Following surgery, the patients were assessed for postoperative requirements for analgesia; return to normal activity; varicocele recurrence; hydrocele formation; scrotal pain at postoperative days 1, 3, and 7; and other complications. Results: Mean age was 24.2±3.4 years in Group I and 25.1±2.1 years in Group II. Mean pain scores at postoperative 1, 3, and 7 days in Group I were (5.20±1.14, 4.60±0.97, and 3.50±0.97, respectively) significantly higher than those of Group II (0.70±0.82, 0.60±0.84, and 0.10±0.32, respectively). Time to return to normal activity was significantly shorter in Group II (3.7±2.1 days) compared with Group I (6.8±3.4 days) (p=0.028). However, the number of recurrences and hydroceles, as a complication of varicocelectomy, was 2 times higher in Group II (10%) than in Group I (5%). Conclusions: We believe that laparoscopic varicocelectomy is a safe, effective, and minimally invasive procedure. Furthermore, reduced postoperative discomfort and earlier return to normal activity are additional advantages of this method. PMID:23477168

Parameter estimation for the exponential-normal convolution model for background correction of affymetrix GeneChip data.

PubMed

McGee, Monnie; Chen, Zhongxue

2006-01-01

There are many methods of correcting microarray data for non-biological sources of error. Authors routinely supply software or code so that interested analysts can implement their methods. Even with a thorough reading of associated references, it is not always clear how requisite parts of the method are calculated in the software packages. However, it is important to have an understanding of such details, as this understanding is necessary for proper use of the output, or for implementing extensions to the model. In this paper, the calculation of parameter estimates used in Robust Multichip Average (RMA), a popular preprocessing algorithm for Affymetrix GeneChip brand microarrays, is elucidated. The background correction method for RMA assumes that the perfect match (PM) intensities observed result from a convolution of the true signal, assumed to be exponentially distributed, and a background noise component, assumed to have a normal distribution. A conditional expectation is calculated to estimate signal. Estimates of the mean and variance of the normal distribution and the rate parameter of the exponential distribution are needed to calculate this expectation. Simulation studies show that the current estimates are flawed; therefore, new ones are suggested. We examine the performance of preprocessing under the exponential-normal convolution model using several different methods to estimate the parameters.

Improved tomographic reconstructions using adaptive time-dependent intensity normalization.

PubMed

Titarenko, Valeriy; Titarenko, Sofya; Withers, Philip J; De Carlo, Francesco; Xiao, Xianghui

2010-09-01

The first processing step in synchrotron-based micro-tomography is the normalization of the projection images against the background, also referred to as a white field. Owing to time-dependent variations in illumination and defects in detection sensitivity, the white field is different from the projection background. In this case standard normalization methods introduce ring and wave artefacts into the resulting three-dimensional reconstruction. In this paper the authors propose a new adaptive technique accounting for these variations and allowing one to obtain cleaner normalized data and to suppress ring and wave artefacts. The background is modelled by the product of two time-dependent terms representing the illumination and detection stages. These terms are written as unknown functions, one scaled and shifted along a fixed direction (describing the illumination term) and one translated by an unknown two-dimensional vector (describing the detection term). The proposed method is applied to two sets (a stem Salix variegata and a zebrafish Danio rerio) acquired at the parallel beam of the micro-tomography station 2-BM at the Advanced Photon Source showing significant reductions in both ring and wave artefacts. In principle the method could be used to correct for time-dependent phenomena that affect other tomographic imaging geometries such as cone beam laboratory X-ray computed tomography.

Cosmic background radiation anisotropy in an open inflation, cold dark matter cosmogony

NASA Technical Reports Server (NTRS)

Kamionkowski, Marc; Ratra, Bharat; Spergel, David N.; Sugiyama, Naoshi

1994-01-01

We compute the cosmic background radiation anisotropy, produced by energy-density fluctuations generated during an early epoch of inflation, in an open cosmological model based on the cold dark matter scenario. At Omega(sub 0) is approximately 0.3-0.4, the Cosmic Background Explorer (COBE) normalized open model appears to be consistent with most observations.

Examining the validity of the ActivPAL monitor in measuring posture and ambulatory movement in children

PubMed Central

2012-01-01

Background Decreasing sedentary activities that involve prolonged sitting may be an important strategy to reduce obesity and other physical and psychosocial health problems in children. The first step to understanding the effect of sedentary activities on children’s health is to objectively assess these activities with a valid measurement tool. Purpose To examine the validity of the ActivPAL monitor in measuring sitting/lying, standing, and walking time, transition counts and step counts in children in a laboratory setting. Methods Twenty five healthy elementary school children (age 9.9 ± 0.3 years; BMI 18.2 ± 1.9; mean ± SD) were randomly recruited across the Auckland region, New Zealand. Children were fitted with ActivPAL monitors and observed during simulated free-living activities involving sitting/lying, standing and walking, followed by treadmill and over-ground activities at various speeds (slow, normal, fast) against video observation (criterion measure). The ActivPAL sit-to-stand and stand-to-sit transition counts and steps were also compared with video data. The accuracy of step counts measured by the ActivPAL was also compared against the New Lifestyles NL-2000 and the Yamax Digi-Walker SW-200 pedometers. Results We observed a perfect correlation between the ActivPAL monitor in time spent sitting/lying, standing, and walking in simulated free-living activities with direct observation. Correlations between the ActivPAL and video observation in total numbers of sit-to-stand and stand-to-sit transitions were high (r = 0.99 ± 0.01). Unlike pedometers, the ActivPAL did not misclassify fidgeting as steps taken. Strong correlations (r = 0.88-1.00) between ActivPAL step counts and video observation in both treadmill and over-ground slow and normal walking were also observed. During treadmill and over-ground fast walking and running, the correlations were low (r = 0.21-0.46). Conclusion The ActivPAL monitor is a valid measurement tool for assessing time spent sitting/lying, standing, and walking, sit-to-stand and stand-to-sit transition counts and step counts in slow and normal walking. The device did not measure accurately steps taken during treadmill and over-ground fast walking and running in children. PMID:23031188

Gravitational force modulates muscle activity during mechanical oscillation of the tibia in humans

PubMed Central

Chang, Shuo-Hsiu; Dudley-Javoroski, Shauna; Shields, Richard K.

2012-01-01

Mechanical oscillation (vibration) is an osteogenic stimulus for bone in animal models and may hold promise as an anti-osteoporosis measure in humans with spinal cord injury (SCI). However, the level of reflex induced muscle contractions associated with various loads (g force) during limb segment oscillation is uncertain. The purpose of this study was to determine whether certain gravitational loads (g forces) at a fixed oscillation frequency (30 Hz) increases muscle reflex activity in individuals with and without SCI. Nine healthy subjects and two individuals with SCI sat with their hip and knee joints at 90° and the foot secured on an oscillation platform. Vertical mechanical oscillations were introduced at 0.3, 0.6, 1.2, 3 and 5g force for 20 seconds at 30 Hz. Non-SCI subjects received the oscillation with and without a 5% MVC background contraction. Peak soleus and tibialis anterior (TA) EMG were normalized to M-max. Soleus and TA EMG were < 2.5% of M-max in both SCI and non-SCI subjects. The greatest EMG occurred at the highest acceleration (5g). Low magnitude mechanical oscillation, shown to enhance bone anabolism in animal models, did not elicit high levels of reflex muscle activity in individuals with and without SCI. These findings support the g force modulated background muscle activity during fixed frequency vibration. The magnitude of muscle activity was low and likely does not influence the load during fixed frequency oscillation of the tibia. PMID:21708472

A Bayesian Method for Identifying Contaminated Detectors in Low-Level Alpha Spectrometers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maclellan, Jay A.; Strom, Daniel J.; Joyce, Kevin E.

2011-11-02

Analyses used for radiobioassay and other radiochemical tests are normally designed to meet specified quality objectives, such relative bias, precision, and minimum detectable activity (MDA). In the case of radiobioassay analyses for alpha emitting radionuclides, a major determiner of the process MDA is the instrument background. Alpha spectrometry detectors are often restricted to only a few counts over multi-day periods in order to meet required MDAs for nuclides such as plutonium-239 and americium-241. A detector background criterion is often set empirically based on experience, or frequentist or classical statistics are applied to the calculated background count necessary to meet amore » required MDA. An acceptance criterion for the detector background is set at the multiple of the estimated background standard deviation above the assumed mean that provides an acceptably small probability of observation if the mean and standard deviation estimate are correct. The major problem with this method is that the observed background counts used to estimate the mean, and thereby the standard deviation when a Poisson distribution is assumed, are often in the range of zero to three counts. At those expected count levels it is impossible to obtain a good estimate of the true mean from a single measurement. As an alternative, Bayesian statistical methods allow calculation of the expected detector background count distribution based on historical counts from new, uncontaminated detectors. This distribution can then be used to identify detectors showing an increased probability of contamination. The effect of varying the assumed range of background counts (i.e., the prior probability distribution) from new, uncontaminated detectors will be is discussed.« less

Simple and rapid assay for effect of the new oral anticoagulant (NOAC) rivaroxaban: preliminary results support further tests with all NOACs

PubMed Central

2014-01-01

Background New oral anticoagulant (NOAC) drugs are known to influence the results of some routine hemostasis tests. Further data are needed to enable routine assessment of the effects of NOAC on clotting parameters in some special circumstances. Methods Following administration of rivaroxaban to patients, at the likely peak and trough activity times, we assessed the effects on prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and clotting time using Russell’s viper venom, and in the presence of phospholipids and calcium reagent available as DVVreagent® and DVVconfirm®. The data were used to determine an adequate NOAC plasma level based on anticoagulant activities expressed as a ratio (patients/normal, R-C). Results DVVconfirm as R-C could be rapidly performed, and the results were reasonably sensitive for rivaroxaban and probably for other FX inhibitors. This assay is not influenced by lupus anticoagulant and heparin, does not require purified NOAC as control, and will measure whole-plasma clotting activity. Conclusions We propose a cut-off R-C value of 4.52 ± 0.33 for safety, but clinical studies are needed to establish whether this cut-off is useful for identifying patients at increased risk of hemorrhage or exhibiting low anticoagulation effect. It also seems possible that normal R-C could indicate an absence of anticoagulant activity when rivaroxaban is discontinued due to episodes of uncontrolled bleeding during anticoagulation or for emergency surgery. PMID:24656069

γH2Ax Expression as a Potential Biomarker Differentiating between Low and High Grade Cervical Squamous Intraepithelial Lesions (SIL) and High Risk HPV Related SIL

PubMed Central

Kefala, Maria; Kottaridi, Christine; Spathis, Aris; Gouloumi, Alina-Roxani; Pouliakis, Abraham; Pappas, Asimakis; Sioulas, Vasileios; Chrelias, Charalambos; Karakitsos, Petros; Panayiotides, Ioannis

2017-01-01

Background γH2AX is a protein biomarker for double-stranded DNA breakage; its expression was studied in cervical squamous intraepithelial lesions and carcinomas. Methods Immunostaining for phospho-γH2AX was performed in sections from histologically confirmed cervical SIL and carcinomas, as well as from normal cervices used as controls. In total, 275 cases were included in the study: 112 low grade SIL (LGSIL), 99 high grade SIL (HGSIL), 24 squamous cell carcinoma (SCC), 12 adenocarcinoma and 28 cervical specimens with no essential lesions. Correlation of histological grading, high risk vs. low risk HPV virus presence, activated vs. non-activated status (by high risk HPV mRNA expression) and γH2AX expression in both basal and surface segments of the squamous epithelium was performed. Results Gradual increase of both basal and surface γH2AX expression was noted up from normal cervices to LGSIL harboring a low risk HPV type, to LGSIL harboring a high risk virus at a non-activated state (p<0.05). Thereafter, both basal and surface γH2AX expression dropped in LGSIL harboring a high risk virus at an activated state and in HGSIL. Conclusions γH2AX could serve as a potential biomarker discriminating between LGSIL and HGSIL, as well as between LGSIL harboring high risk HPV at an activated state. PMID:28118377

Objective Quantification of Physical Activity in Bariatric Surgery Candidates and Normal-Weight Controls

PubMed Central

Bond, Dale S.; Jakicic, John M.; Vithiananthan, Sivamainthan; Thomas, J. Graham; Leahey, Tricia M.; Sax, Harry C.; Pohl, Dieter; Roye, G.D.; Ryder, Beth A.; Wing, Rena R.

2009-01-01

Background Physical activity (PA) is an important component of weight loss programs and may be encouraged for severely obese patients undergoing bariatric surgery. However, few studies have determined the amount and intensity of activities undertaken preoperatively by bariatric surgery patients using objective measures. Methods Using RT3 tri-axial accelerometers, this study compared 38 bariatric surgery candidates and 20 normal-weight controls on: 1) activity counts/hour; 2) minutes/day spent in moderate-to-vigorous intensity PA (MVPA) and vigorous intensity PA (VPA); and 3) level of compliance with national recommendations to accumulate 150 minutes/week of MVPA in bouts ≥ 10 minutes. Results Surgery candidates, compared to controls, recorded significantly (Ps < 0.01) fewer activity counts/hour (13799 ± 3758 vs 19462 ± 4259) and spent fewer minutes/day engaged in MVPA (26.4 ± 23.0 vs 52.4 ± 24.7) and VPA (1.2 ± 3.4 vs 11.8 ± 9.0). More than two-thirds (68%) of surgery candidates versus 13% of NW did not accumulate any MVPA in bouts ≥ 10 minutes and only 4.5% of Ob met the weekly MVPA recommendation compared to 40% of NW. Conclusion Bariatric surgery candidates have low PA levels and rarely engage in PA bouts of sufficient duration and intensity to maintain and improve health. Additional research is needed to determine how best to increase PA in bariatric surgery candidates. PMID:19837009

Muscular Activation During Plyometric Exercises in 90° of Glenohumeral Joint Abduction

PubMed Central

Ellenbecker, Todd S.; Sueyoshi, Tetsuro; Bailie, David S.

2015-01-01

Background: Plyometric exercises are frequently used to increase posterior rotator cuff and periscapular muscle strength and simulate demands and positional stresses in overhead athletes. The purpose of this study was to provide descriptive data on posterior rotator cuff and scapular muscle activation during upper extremity plyometric exercises in 90° of glenohumeral joint abduction. Hypothesis: Levels of muscular activity in the posterior rotator cuff and scapular stabilizers will be high during plyometric shoulder exercises similar to previously reported electromyographic (EMG) levels of shoulder rehabilitation exercises. Study Design: Descriptive laboratory study. Methods: Twenty healthy subjects were tested using surface EMG during the performance of 2 plyometric shoulder exercises: prone external rotation (PERP) and reverse catch external rotation (RCP) using a handheld medicine ball. Electrode application included the upper and lower trapezius (UT and LT, respectively), serratus anterior (SA), infraspinatus (IN), and the middle and posterior deltoid (MD and PD, respectively) muscles. A 10-second interval of repetitive plyometric exercise (PERP) and 3 repetitions of RCP were sampled. Peak and average normalized EMG data were generated. Results: Normalized peak and average IN activity ranged between 73% and 102% and between 28% and 52% during the plyometric exercises, respectively, with peak and average LT activity measured between 79% and 131% and between 31% and 61%. SA activity ranged between 76% and 86% for peak and between 35% and 37% for average activity. Muscular activity levels in the MD and PD ranged between 49% and 72% and between 12% and 33% for peak and average, respectively. Conclusion: Moderate to high levels of muscular activity were measured in the rotator cuff and scapular stabilizers during these plyometric exercises with the glenohumeral joint abducted 90°. PMID:25553216

The Tension-sensitive Ion Transport Activity of MSL8 is Critical for its Function in Pollen Hydration and Germination.

PubMed

Hamilton, Eric S; Haswell, Elizabeth S

2017-07-01

All cells respond to osmotic challenges, including those imposed during normal growth and development. Mechanosensitive (MS) ion channels provide a conserved mechanism for regulating osmotic forces by conducting ions in response to increased membrane tension. We previously demonstrated that the MS ion channel MscS-Like 8 (MSL8) is required for pollen to survive multiple osmotic challenges that occur during the normal process of fertilization, and that it can inhibit pollen germination. However, it remained unclear whether these physiological functions required ion flux through a mechanically gated channel provided by MSL8. We introduced two point mutations into the predicted pore-lining domain of MSL8 that disrupted normal channel function in different ways. The Ile711Ser mutation increased the tension threshold of the MSL8 channel while leaving conductance unchanged, and the Phe720Leu mutation severely disrupted the MSL8 channel. Both of these mutations impaired the ability of MSL8 to preserve pollen viability during hydration and to maintain the integrity of the pollen tube when expressed at endogenous levels. When overexpressed in an msl8-4 null background, MSL8I711S could partially rescue loss-of-function phenotypes, while MSL8F720L could not. When overexpressed in the wild-type Ler background, MSL8I711S suppressed pollen germination, similar to wild-type MSL8. In contrast, MSL8F720L failed to suppress pollen germination and increased pollen bursting, thereby phenocopying the msl8-4 mutant. Thus, an intact MSL8 channel is required for normal pollen function during hydration and germination. These data establish MSL8 as the first plant MS channel to fulfill previously established criteria for assignment as a mechanotransducer. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Stability of Early EEG Background Patterns After Pediatric Cardiac Arrest.

PubMed

Abend, Nicholas S; Xiao, Rui; Kessler, Sudha Kilaru; Topjian, Alexis A

2018-05-01

We aimed to determine whether EEG background characteristics remain stable across discrete time periods during the acute period after resuscitation from pediatric cardiac arrest. Children resuscitated from cardiac arrest underwent continuous conventional EEG monitoring. The EEG was scored in 12-hour epochs for up to 72 hours after return of circulation by an electroencephalographer using a Background Category with 4 levels (normal, slow-disorganized, discontinuous/burst-suppression, or attenuated-featureless) or 2 levels (normal/slow-disorganized or discontinuous/burst-suppression/attenuated-featureless). Survival analyses and mixed-effects ordinal logistic regression models evaluated whether the EEG remained stable across epochs. EEG monitoring was performed in 89 consecutive children. When EEG was assessed as the 4-level Background Category, 30% of subjects changed category over time. Based on initial Background Category, one quarter of the subjects changed EEG category by 24 hours if the initial EEG was attenuated-featureless, by 36 hours if the initial EEG was discontinuous or burst-suppression, by 48 hours if the initial EEG was slow-disorganized, and never if the initial EEG was normal. However, regression modeling for the 4-level Background Category indicated that the EEG did not change over time (odds ratio = 1.06, 95% confidence interval = 0.96-1.17, P = 0.26). Similarly, when EEG was assessed as the 2-level Background Category, 8% of subjects changed EEG category over time. However, regression modeling for the 2-level category indicated that the EEG did not change over time (odds ratio = 1.02, 95% confidence interval = 0.91-1.13, P = 0.75). The EEG Background Category changes over time whether analyzed as 4 levels (30% of subjects) or 2 levels (8% of subjects), although regression analyses indicated that no significant changes occurred over time for the full cohort. These data indicate that the Background Category is often stable during the acute 72 hours after pediatric cardiac arrest and thus may be a useful EEG assessment metric in future studies, but that some subjects do have EEG changes over time and therefore serial EEG assessments may be informative.

cAMP controls rod photoreceptor sensitivity via multiple targets in the phototransduction cascade

PubMed Central

Astakhova, Luba A.; Samoiliuk, Evgeniia V.; Govardovskii, Victor I.

2012-01-01

In early studies, both cyclic AMP (cAMP) and cGMP were considered as potential secondary messengers regulating the conductivity of the vertebrate photoreceptor plasma membrane. Later discovery of the cGMP specificity of cyclic nucleotide–gated channels has shifted attention to cGMP as the only secondary messenger in the phototransduction cascade, and cAMP is not considered in modern schemes of phototransduction. Here, we report evidence that cAMP may also be involved in regulation of the phototransduction cascade. Using a suction pipette technique, we recorded light responses of isolated solitary rods from the frog retina in normal solution and in the medium containing 2 µM of adenylate cyclase activator forskolin. Under forskolin action, flash sensitivity rose more than twofold because of a retarded photoresponse turn-off. The same concentration of forskolin lead to a 2.5-fold increase in the rod outer segment cAMP, which is close to earlier reported natural day/night cAMP variations. Detailed analysis of cAMP action on the phototransduction cascade suggests that several targets are affected by cAMP increase: (a) basal dark phosphodiesterase (PDE) activity decreases; (b) at the same intensity of light background, steady background-induced PDE activity increases; (c) at light backgrounds, guanylate cyclase activity at a given fraction of open channels is reduced; and (d) the magnitude of the Ca2+ exchanger current rises 1.6-fold, which would correspond to a 1.6-fold elevation of [Ca2+]in. Analysis by a complete model of rod phototransduction suggests that an increase of [Ca2+]in might also explain effects (b) and (c). The mechanism(s) by which cAMP could regulate [Ca2+]in and PDE basal activity is unclear. We suggest that these regulations may have adaptive significance and improve the performance of the visual system when it switches between day and night light conditions. PMID:23008435

Inhalation exposures due to radon and thoron ((222)Rn and (220)Rn): Do they differ in high and normal background radiation areas in India?

PubMed

Mishra, Rosaline; Sapra, B K; Prajith, R; Rout, R P; Jalaluddin, S; Mayya, Y S

2015-09-01

In India, High Background Radiation Areas (HBRAs) due to enhanced levels of naturally occurring radionuclides in soil (thorium and, to a lesser extent, uranium), are located along some parts of the coastal tracts viz. the coastal belt of Kerala, Tamilnadu and Odisha. It is conjectured that these deposits will result in higher emissions of radon isotopes ((222)Rn and (220)Rn) and their daughter products as compared to Normal Background Radiation Areas (NBRAs). While the annual external dose rates contributed by gamma radiations in these areas are about 5-10 times higher, the extent of increase in the inhalation dose rates attributable to (222)Rn and (220)Rn and their decay products is not well quantified. Towards this, systematic indoor surveys were conducted wherein simultaneous measurements of time integrated (222)Rn and (220)Rn gas and their decay product concentrations was carried out in around 800 houses in the HBRAs of Kerala and Odisha to estimate the inhalation doses. All gas measurements were carried out using pin-hole cup dosimeters while the progeny measurements were with samplers and systems based on the Direct radon/thoron Progeny sensors (DRPS/DTPS). To corroborate these passive measurements of decay products concentrations, active sampling was also carried out in a few houses. The results of the surveys provide a strong evidence to conclude that the inhalation doses due to (222)Rn and (220)Rn gas and their decay products in these HBRAs are in the same range as observed in the NBRAs in India. Copyright © 2015 Elsevier Ltd. All rights reserved.

Overexpression of the Ubiquilin-4 (UBQLN4) is Associated with Cell Cycle Arrest and Apoptosis in Human Normal Gastric Epithelial Cell Lines GES-1 Cells by Activation of the ERK Signaling Pathway

PubMed Central

Huang, Shengkai; Dong, Xin; Wang, Jia; Ding, Jie; Li, Yan; Li, Dongdong; Lin, Hong; Wang, Wenjie; Zhao, Mei

2018-01-01

Background Ubiquilin-4 (UBQLN4) is a component of the ubiquitin-proteasome system and regulates the degradation of many proteins implicated in pathological conditions. The aim of this study was to determine the role of UBQLN4 in regulating the proliferation and survival of the normal gastric epithelial cell line GES-1. Material/Methods We constructed GES-1 lines stably overexpressing UBQLN4 by lentiviral infection. Cell proliferation, apoptosis, and the cell cycle were analyzed using the MTT assay and flow cytometric assays. Phosphorylation of ERK, JNK, p38, and expression of cyclin D1 were detected by western blot analysis. Results Overexpression of UBQLN4 significantly reduced proliferation and induced G2/M phase arrest and apoptosis in GES-1 cells. Moreover, upregulation of UBQLN4 increased the expression of cyclin D1 and phosphorylated ERK, but not JNK or p38. Conclusions These data suggest that UBQLN4 may induce cell cycle arrest and apoptosis via activation of the ERK pathway and upregulation of cyclin D1 in GES-1 cells. PMID:29807370

Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity walls using a novel cathepsin-activated fluorescent imaging system.

PubMed

Smith, Barbara L; Gadd, Michele A; Lanahan, Conor R; Rai, Upahvan; Tang, Rong; Rice-Stitt, Travis; Merrill, Andrea L; Strasfeld, David B; Ferrer, Jorge M; Brachtel, Elena F; Specht, Michelle C

2018-06-09

Obtaining tumor-free surgical margins is critical to prevent recurrence in breast-conserving surgery but it remains challenging. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor. Lumpectomy cavity walls and excised specimens of breast cancer lumpectomy patients were assessed with the LUM Imaging System (Lumicell, Inc., Wellesley MA) with and without intravenous LUM015, a cathepsin-activatable fluorescent agent. Fluorescence at potential sites of residual tumor was evaluated with a sterile hand-held probe, displayed on a monitor and correlated with histopathology. Background autofluorescence was assessed in excised specimens from 9 patients who did not receive LUM015. In vivo lumpectomy cavities and excised specimens were then imaged in 15 women undergoing breast cancer surgery who received no LUM015, 0.5, or 1 mg/kg LUM015 (5 women per dose). Among these, 11 patients had invasive carcinoma with ductal carcinoma in situ (DCIS) and 4 had only DCIS. Image acquisition took 1 s for each 2.6-cm-diameter surface. No significant background normal breast fluorescence was identified. Elevated fluorescent signal was seen from invasive cancers and DCIS. Mean tumor-to-normal signal ratios were 4.70 ± 1.23 at 0.5 mg/kg and 4.22 ± 0.9 at 1.0 mg/kg (p = 0.54). Tumor was distinguished from normal tissue in pre-and postmenopausal women and readings were not affected by breast density. Some benign tissues produced fluorescent signal with LUM015. The LUM Imaging System allows rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.

Different apoptotic effects of [Pt(O,O′-acac)(γ-acac)(DMS)] and cisplatin on normal and cancerous human epithelial breast cells in primary culture

PubMed Central

Vetrugno, Carla; Muscella, Antonella; Fanizzi, Francesco Paolo; Cossa, Luca Giulio; Migoni, Danilo; De Pascali, Sandra Angelica; Marsigliante, Santo

2014-01-01

Background and Purpose The aim of this study was to determine whether [platinum (Pt)(O,O′-acetylacetonate (acac))(γ-acac)(dimethylsulphide (DMS))] is differentially cytotoxic in normal and cancer cells, and to measure comparative levels of cytotoxicity compared with cisplatin in the same cells. Experimental Approach We performed experiments on cancerous and normal epithelial breast cells in primary culture obtained from the same patients. The apoptotic effects [Pt(O,O′-acac)(γ-acac)(DMS)] and cisplatin in cancerous and normal breast cells were compared. Key Results Cancer cells were more sensitive to [Pt(O,O′-acac)(γ-acac)(DMS)] (IC50 = 5.22 ± 1.2 μmol·L−1) than normal cells (IC50 = 116.9 ± 8.8 μmol·L−1). However, the difference was less strong when cisplatin was used (IC50 = 96.0 ± 6.9 and 61.9 ± 6.1 μmol·L−1 for cancer and normal cells respectively). Both compounds caused reactive oxygen species (ROS) production with different mechanisms: [Pt(O,O′-acac)(γ-acac)(DMS)] quickly activated NAD(P)H oxidase while cisplatin caused a slower formation of mitochondrial ROS. Cisplatin and [Pt(O,O′-acac)(γ-acac)(DMS)] caused activation of caspases, proteolysis of PARP and modulation of Bcl-2, Bax and Bid. [Pt(O,O′-acac)(γ-acac)(DMS)] also caused leakage of cytochrome c from the mitochondria. Overall, these processes proceeded more quickly in cells treated with [Pt(O,O′-acac)(γ-acac)(DMS)] compared with cisplatin. [Pt(O,O′-acac)(γ-acac)(DMS)] effects were faster and quantitatively greater in cancer than in normal cells. [Pt(O,O′-acac)(γ-acac)(DMS)] caused a fast decrease of mitochondrial membrane potential, especially in cancer cells. Conclusions and Implications [Pt(O,O′-acac)(γ-acac)(DMS)] was specific to breast cancer cells in primary culture, and this observation makes this compound potentially more interesting than cisplatin. PMID:24990093

Subependymal heterotopia: a distinct neuronal migration disorder associated with epilepsy.

PubMed Central

Raymond, A A; Fish, D R; Stevens, J M; Sisodiya, S M; Alsanjari, N; Shorvon, S D

1994-01-01

Subependymal heterotopia has recently been recognised as a cause of epilepsy, but the clinical and investigational features have not been fully described. The clinical, psychometric, imaging, and electroencephalographic features of 13 adult patients with subependymal heterotopia and epilepsy have been reviewed. Age at seizure onset ranged from 18 months to 20 years (median 13 years). There were significantly more female (12) than male (1) patients (p < 0.01). Diagnosis of subependymal heterotopia was made by MRI in 11 patients and CT in two. The heterotopic grey matter was nodular in 11 patients and diffuse in two; bilateral in eight and unilateral in five. There were significantly more patients with predominant right than left cerebral hemisphere involvement (p < 0.01). The most commonly involved site was the occipital horn of the lateral ventricles (10 of 13 patients). Eleven patients presented with partial epilepsy, 10 of whom also had secondarily generalised seizures. The clinical description of the seizures often suggested either an occipital (four patients) or temporal (five patients) onset. Two patients presented with absence attacks without clear focal features. Patients demonstrated normal early milestones (12 of 13 patients), including normal motor development (all patients) and average or above average intelligence (10 of 13 patients). An EEG examination showed normal background activity in all but two patients, one of whom had large intracranial haematomas. Epileptiform activity was usually widespread (10 of 13 patients) and in three patients, there was generalised 3-Hz spike and wave activity that had previously led to an erroneous diagnosis of concomitant primary generalised epilepsy. Onset of epilepsy in the second decade of life, normal developmental milestones and intelligence, and the finding of an overwhelming female preponderance differentiates subependymal heterotopia from other cortical dysgeneses. The female preponderance supports the importance of the X chromosome and sex steroids in the maturation and development of the cerebral cortex. Images PMID:7931380

Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin

PubMed Central

Huang, Yuanshen; Wang, Yang; Yu, Jie; Gao, Min; Levings, Megan; Wei, Shencai; Zhang, Shengquan; Xu, Aie; Su, Mingwan; Dutz, Jan; Zhang, Xuejun; Zhou, Youwen

2012-01-01

Background Vitiligo is characterized by the death of melanocytes in the skin. This is associated with the presence of T cell infiltrates in the lesional borders. However, at present, there is no detailed and systematic characterization on whether additional cellular or molecular changes are present inside vitiligo lesions. Further, it is unknown if the normal appearing non-lesional skin of vitiligo patients is in fact normal. The purpose of this study is to systematically characterize the molecular and cellular characteristics of the lesional and non-lesional skin of vitiligo patients. Methods and Materials Paired lesional and non-lesional skin biopsies from twenty-three vitiligo patients and normal skin biopsies from sixteen healthy volunteers were obtained with informed consent. The following aspects were analyzed: (1) transcriptome changes present in vitiligo skin using DNA microarrays and qRT-PCR; (2) abnormal cellular infiltrates in vitiligo skin explant cultures using flow cytometry; and (3) distribution of the abnormal cellular infiltrates in vitiligo skin using immunofluorescence microscopy. Results Compared with normal skin, vitiligo lesional skin contained 17 genes (mostly melanocyte-specific genes) whose expression was decreased or absent. In contrast, the relative expression of 13 genes was up-regulated. The up-regulated genes point to aberrant activity of the innate immune system, especially natural killer cells in vitiligo. Strikingly, the markers of heightened innate immune responses were also found to be up-regulated in the non-lesional skin of vitiligo patients. Conclusions and Clinical Implications As the first systematic transcriptome characterization of the skin in vitiligo patients, this study revealed previously unknown molecular markers that strongly suggest aberrant innate immune activation in the microenvironment of vitiligo skin. Since these changes involve both lesional and non-lesional skin, our results suggest that therapies targeting the entire skin surface may improve treatment outcomes. Finally, this study revealed novel mediators that may facilitate future development of vitiligo therapies. PMID:23251420

Some aspects of the modular organization of the primary visual cortex of the cat: patterns of cytochrome oxidase activity.

PubMed

Merkul'eva, N S; Makarov, F N

2008-10-01

The distribution of the enzyme cytochrome oxidase (CO) in continuous series of parasagittal sections from field 17 and frontal sections of the dorsal nucleus of the lateral geniculate body (LGB) from normal kittens and adult cats was studied. In all cats apart from neonates, layer IV showed regularly alternating areas with above-background levels of CO activity ("spots"). There was a significant increase in the contrast of the "spots" from days 13 to 21, which was followed by a significant decrease from days 48 to 93. These changes coincided with ontogenetic changes in the level of visual system plasticity. There were no differences in CO activity between layers A and A1 of the dorsal nucleus of the LGB. It is suggested that the non-uniform distribution of the level of functional activity of neurons in field 17 reflects the formation of columnar cortical structures during the critical period of postnatal ontogenesis.

Cross-correlating Cosmic IR and X-ray Background Fluctuations: Evidence of Significant Black Hole Populations Among the CIB Sources

NASA Technical Reports Server (NTRS)

Cappelluti, N.; Kashlinsky, A.; Arendt, R. G.; Comastri, A.; Fazio, G. G.; Finoguenov, A.; Hasinger, G.; Mather, J. C.; Miyaji, T; Moseley, S. H.

2013-01-01

In order to understand the nature of the sources producing the recently uncovered cosmic infrared background (CIB) fluctuations, we study cross-correlations between the fluctuations in the source-subtracted CIB from Spitzer/IRAC data and the unresolved cosmic X-ray background from deep Chandra observations. Our study uses data from the EGS/AEGIS field, where both data sets cover an approx = 8' x 45' region of the sky. Our measurement is the cross-power spectrum between the IR and X-ray data. The cross-power signal between the IRAC maps at 3.6 micron and 4.5 micron and the Chandra [0.5-2] keV data has been detected, at angular scales approx >20'', with an overall significance of approx = 3.8 sigma and approx. = 5.6 sigma, respectively. At the same time we find no evidence of significant cross-correlations at the harder Chandra bands. The cross-correlation signal is produced by individual IR sources with 3.6 micron and 4.5 micron magnitudes m(sub AB) approx. > 25-26 and [0.5-2] keV X-ray fluxes << 7 × 10(exp -177 erg sq. cm/ s. We determine that at least 15%-25% of the large scale power of the CIB fluctuations is correlated with the spatial power spectrum of the X-ray fluctuations. If this correlation is attributed to emission from accretion processes at both IR and X-ray wavelengths, this implies a much higher fraction of accreting black holes than among the known populations. We discuss the various possible origins for the cross-power signal and show that neither local foregrounds nor the known remaining normal galaxies and active galactic nuclei can reproduce the measurements. These observational results are an important new constraint on theoretical modeling of the near-IR CIB fluctuations. local foregrounds, nor the known remaining normal galaxies and active galactic nuclei (AGN) can reproduce the measurements. These observational results are an important new constraint on theoretical modeling of the near-IR CIB fluctuations

How Does Circadian Rhythm Impact Salt Sensitivity of Blood Pressure in Mice? A Study in Two Close C57Bl/6 Substrains.

PubMed

Combe, Roy; Mudgett, John; El Fertak, Lahcen; Champy, Marie-France; Ayme-Dietrich, Estelle; Petit-Demoulière, Benoit; Sorg, Tania; Herault, Yann; Madwed, Jeffrey B; Monassier, Laurent

2016-01-01

Mouse transgenesis has provided the unique opportunity to investigate mechanisms underlying sodium kidney reabsorption as well as end organ damage. However, understanding mouse background and the experimental conditions effects on phenotypic readouts of engineered mouse lines such as blood pressure presents a challenge. Despite the ability to generate high sodium and chloride plasma levels during high-salt diet, observed changes in blood pressure are not consistent between wild-type background strains and studies. The present work was designed in an attempt to determine guidelines in the field of salt-induced hypertension by recording continuously blood pressure by telemetry in mice submitted to different sodium and potassium loaded diets and changing experimental conditions in both C57BL/6N and C57BL/6J mice strain (Normal salt vs. Low salt vs. High-salt/normal potassium vs. High salt/low potassium, standard vs. modified light cycle, Non-invasive tail cuff blood pressure vs. telemetry). In this study, we have shown that, despite a strong blood pressure (BP) basal difference between C57BL/6N and C57BL/6J mice, High salt/normal potassium diet increases BP and heart rate during the active phase only (dark period) in the same extent in both strains. On the other hand, while potassium level has no effect on salt-induced hypertension in C57BL/6N mice, high-salt/low potassium diet amplifies the effect of the high-salt challenge only in C57BL/6J mice. Indeed, in this condition, salt-induced hypertension can also be detected during light period even though this BP increase is lower compared to the one occurring during the dark period. Finally, from a methodological perspective, light cycle inversion has no effect on this circadian BP phenotype and tail-cuff method is less sensitive than telemetry to detect BP phenotypes due to salt challenges. Therefore, to carry investigations on salt-induced hypertension in mice, chronic telemetry and studies in the active phase are essential prerequisites.

Characteristic changes in brain electrical activity due to chronic hypoxia in patients with obstructive sleep apnea syndrome (OSAS): a combined EEG study using LORETA and omega complexity.

PubMed

Toth, Marton; Faludi, Bela; Wackermann, Jiri; Czopf, Jozsef; Kondakor, Istvan

2009-11-01

EEG background activity of patients with obstructive sleep apnea syndrome (OSAS, N = 25) was compared to that of normal controls (N = 14) to reflect alterations of brain electrical activity caused by chronic intermittent hypoxia in OSAS. Global and regional (left vs. right, anterior vs. posterior) measures of spatial complexity (Omega) were used to characterize the degree of spatial synchrony of EEG. Low resolution electromagnetic tomography (LORETA) was used to localize generators of EEG activity in separate frequency bands. Comparing patients to controls, lower Omega complexity was found globally and in the right hemisphere. Using LORETA, an increased medium frequency activity was seen bilaterally in the precuneus, paracentral and posterior cingulate cortex. These findings indicate that alterations caused by chronic hypoxia in brain electrical activity in regions associated with influencing emotional regulation, long-term memory and the default mode network. Global synchronization (lower Omega complexity) may indicate a significantly reduced number of relatively independent, parallel neural processes due to chronic global hypoxic state in apneic patients as well as over the right hemisphere.

Plasmin-dependent proteolysis of Tissue Factor Pathway Inhibitor in a mouse model of endotoxemia

PubMed Central

Lupu, Cristina; Herlea, Oana; Tang, Haiwang; Lijnen, Roger H.; Lupu, Florea

2012-01-01

Summary Background Development of a procoagulant state in sepsis, due to aberrant expression of tissue factor (TF) and sharp decrease of its major inhibitor tissue factor pathway inhibitor (TFPI), could lead to microthrombotic organ failure. The mechanism for the decline of TFPI activity in the lung could involve plasmin-mediated cleavage of the inhibitor. Objective To investigate the effect of plasmin generation on lung-associated TFPI activity, in normal conditions and during infusion of endotoxin (LPS) in mice. Methods Plasmin generation and TFPI activity were assayed in the lungs of mice deficient of tissue-type plasminogen activator (t-PA) or plasminogen (Plg), at 2-hrs after LPS or saline injection. Results The sharp loss of lung-associated TFPI activity at 2-hrs post LPS paralleled the abrupt increase of plasmin generation. TFPI activity was significantly retained in both t-PA-/- and Plg-/- mice, which are unable to generate plasmin. Conclusion The increased plasmin generation during the early stages of sepsis could cleave/inactivate TFPI and thus lead to thrombotic complications. PMID:23106863

Increased longitudinal contractility and diastolic function at rest in well-trained amateur Marathon runners: a speckle tracking echocardiography study

PubMed Central

2014-01-01

Background Regular physical activity reduces cardiovascular risk. There is concern that Marathon running might acutely damage the heart. It is unknown to what extent intensive physical endurance activity influences the cardiac mechanics at resting condition. Methods Eighty-four amateur marathon runners (43 women and 41 men) from Berlin-Brandenburg area who had completed at least one marathon previously underwent clinical examination and echocardiography at least 10 days before the Berlin Marathon at rest. Standard transthoracic echocardiography and 2D strain and strain rate analysis were performed. The 2D Strain and strain rate values were compared to previous published data of healthy untrained individuals. Results The average global longitudinal peak systolic strain of the left ventricle was -23 +/- 2% with peak systolic strain rate -1.39 +/- 0.21/s, early diastolic strain rate 2.0 +/- 0.40/s and late diastolic strain rate 1.21 +/- 0.31/s. These values are significantly higher compared to the previous published values of normal age-adjusted individuals. In addition, no age-related decline of longitudinal contractility in well-trained athletes was observed. Conclusions There is increased overall longitudinal myocardial contractility at rest in experienced endurance athletes compared to the published normal values in the literature indicating a preserved and even supra-normal contractility in the athletes. There is no age dependent decline of the longitudinal 2D Strain values. This underlines the beneficial effects of regular physical exercise even in advanced age. PMID:24571726

10 CFR 600.325 - Intellectual property.

Code of Federal Regulations, 2011 CFR

2011-01-01

... of rights to data and to inventions conceived or first actually reduced to practice in the course of... award. (3) Special Provision. Normally, an award will not include a background patent and data provision... rights data and/or restricted computer software, may be included. Inclusion of a background patent and/or...

10 CFR 600.325 - Intellectual property.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of rights to data and to inventions conceived or first actually reduced to practice in the course of... award. (3) Special Provision. Normally, an award will not include a background patent and data provision... rights data and/or restricted computer software, may be included. Inclusion of a background patent and/or...

Impact of Sociocultural Background and Assessment Data Upon School Psychologists' Decisions.

ERIC Educational Resources Information Center

Huebner, E. Scott; Cummings, Jack A.

1985-01-01

Psychologists (N=56) participated in an adapted version of Algozzine and Ysseldyke's (1981) diagnostic simulation to investigate the effects of sociocultural background (rural vs. suburban) and assessment data (normal vs. learning disabled) on educational decisions. Findings suggest school psychologists utilize multiple sources of information but…

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Science.gov Websites

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Flavonoids Activated Caspases for Apoptosis in Human Glioblastoma T98G and U87MG Cells But Not in Human Normal Astrocytes

PubMed Central

Das, Arabinda; Banik, Naren L.; Ray, Swapan K.

2011-01-01

BACKGROUND Human glioblastoma is a deadly brain cancer that continues to defy all current therapeutic strategies. We induced apoptosis in human glioblastoma T98G and U87MG cells following treatment with apigenin (APG), (−)-epigallocatechin (EGC), (−)-epigallocatechin-3-gallate (EGCG), and genistein (GST) that did not induce apoptosis in human normal astrocytes (HNA). METHODS Induction of apoptosis was examined using Wright staining and ApopTag assay. Production of reactive oxygen species (ROS) and increase in intracellular free [Ca2+] were measured by fluoresent probes. Analysis of mRNA and Western blotting indicated increases in expression and activities of the stress kinases and cysteine proteases for apoptosis. JC-1 showed changes in mitochondrial membrane potential (ΔΨm) and use of specific inhibitors confirmed activation of kinases and proteases in apoptosis. RESULTS Treatment of glioblastoma cells with APG, EGC, EGCG, or GST triggered ROS production that induced apoptosis with phosphorylation of p38 MAPK and activation of the redox-sensitive JNK1 pathway. Pretreatment of cells with ascorbic acid attenuated ROS production and p38 MAPK phosphorylation. Increases in intracellular free [Ca2+] and activation of caspase-4 indicated involvement of endoplasmic reticulum stress in apoptosis. Other events in apoptosis included overexpression of Bax, loss of ΔΨm, mitochondrial release of cytochrome c and Smac into the cytosol, down regulation of baculoviral inhibitor-of-apoptosis repeat containing proteins, and activation of calpain, caspase-9, and caspase-3. EGC and EGCG also induced caspase-8 activity. APG, EGC, EGCG, or GST did not induce apoptosis in HNA. CONCLUSION Results strongly suggest that flavonoids are potential therapeutic agents for induction of apoptosis in human glioblastoma cells. PMID:19894226

Exploratory factor analysis for differentiating sensory and mechanical variables related to muscle-tendon unit elongation

PubMed Central

Chagas, Mauro H.; Magalhães, Fabrício A.; Peixoto, Gustavo H. C.; Pereira, Beatriz M.; Andrade, André G. P.; Menzel, Hans-Joachim K.

2016-01-01

ABSTRACT Background Stretching exercises are able to promote adaptations in the muscle-tendon unit (MTU), which can be tested through physiological and biomechanical variables. Identifying the key variables in MTU adaptations is crucial to improvements in training. Objective To perform an exploratory factor analysis (EFA) involving the variables often used to evaluate the response of the MTU to stretching exercises. Method Maximum joint range of motion (ROMMAX), ROM at first sensation of stretching (FSTROM), peak torque (torqueMAX), passive stiffness, normalized stiffness, passive energy, and normalized energy were investigated in 36 participants during passive knee extension on an isokinetic dynamometer. Stiffness and energy values were normalized by the muscle cross-sectional area and their passive mode assured by monitoring the EMG activity. Results EFA revealed two major factors that explained 89.68% of the total variance: 53.13% was explained by the variables torqueMAX, passive stiffness, normalized stiffness, passive energy, and normalized energy, whereas the remaining 36.55% was explained by the variables ROMMAX and FSTROM. Conclusion This result supports the literature wherein two main hypotheses (mechanical and sensory theories) have been suggested to describe the adaptations of the MTU to stretching exercises. Contrary to some studies, in the present investigation torqueMAX was significantly correlated with the variables of the mechanical theory rather than those of the sensory theory. Therefore, a new approach was proposed to explain the behavior of the torqueMAX during stretching exercises. PMID:27437715

The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?

PubMed Central

2010-01-01

Background High concentrations of recombinant activated factor VII (rFVIIa) can stop bleeding in hemophilic patients. However the rFVIIa dose needed for stopping haemhorrage in off-label indications is unknown. Since thrombin is the main hemostatic agent, this study investigated the effect of rFVIIa and tissue factor (TF) on thrombin generation (TG) in vitro. Methods Lag time (LT), time to peak (TTP), peak TG (PTG), and area under the curve after 35 min (AUCo-35 min) with the calibrated automated thrombography was used to evaluate TG. TG was assayed in platelet-rich plasma (PRP) samples from 29 healthy volunteers under basal conditions and after platelet stimulation with 5.0 μg/ml, 2.6 μg/ml, 0.5 μg/ml, 0.25 μg/ml, and 0.125 μg/ml rFVIIa alone and in normal platelet-poor plasma (PPP) samples from 22 healthy volunteers, rFVIIa in combination with various concentrations of TF (5.0, 2.5, 1.25 and 0.5 pM). Results In PRP activated by rFVIIa, there was a statistically significant increase in TG compared to basal values. A significant TF dose-dependent shortening of LT and increased PTG and AUCo→35 min were obtained in PPP. The addition of rFVIIa increased the effect of TF in shorting the LT and increasing the AUCo→35 min with no effect on PTG but were independent of rFVIIa concentration. Conclusion Low concentrations of rFVIIa were sufficient to form enough thrombin in normal PRP or in PPP when combined with TF, and suggest low concentrations for normalizing hemostasis in off-label indications. PMID:20444280

Influence of kidney function on risk of supratherapeutic international normalized ratio-related hemorrhage in warfarin users: a prospective cohort study

USDA-ARS?s Scientific Manuscript database

Background: Anticoagulation management is difficult in chronic kidney disease, with frequent supratherapeutic international normalized ratios (INRs >/= 4) increasing hemorrhagic risk. We evaluated whether the interaction of INR and lower estimated glomerular filtration rate (eGFR) increases hemorrha...

Activatable fluorescent probes in fluorescence-guided surgery: Practical considerations.

PubMed

Mochida, Ai; Ogata, Fusa; Nagaya, Tadanobu; Choyke, Peter L; Kobayashi, Hisataka

2018-02-15

Fluorescence-guided imaging during surgery is a promising technique that is increasingly used to aid surgeons in identifying sites of tumor and surgical margins. Of the two types of fluorescent probes, always-on and activatable, activatable probes are preferred because they produce higher target-to-background ratios, thus improving sensitivity compared with always-on probes that must contend with considerable background signal. There are two types of activatable probes: 1) enzyme-reactive probes that are normally quenched but can be activated after cleavage by cancer-specific enzymes (activity-based probes) and 2) molecular-binding probes which use cancer targeting moieties such as monoclonal antibodies to target receptors found in abundance on cancers and are activated after internalization and lysosomal processing (binding-based probes). For fluorescence-guided intraoperative surgery, enzyme-reactive probes are superior because they can react quickly, require smaller dosages especially for topical applications, have limited side effects, and have favorable pharmacokinetics. Enzyme-reactive probes are easier to use, fit better into existing work flows in the operating room and have minimal toxicity. Although difficult to prove, it is assumed that the guidance provided to surgeons by these probes results in more effective surgeries with better outcomes for patients. In this review, we compare these two types of activatable fluorescent probes for their ease of use and efficacy. Published by Elsevier Ltd.

Drosophila Uri, a PP1α binding protein, is essential for viability, maintenance of DNA integrity and normal transcriptional activity

PubMed Central

Kirchner, Jasmin; Vissi, Emese; Gross, Sascha; Szoor, Balazs; Rudenko, Andrey; Alphey, Luke; White-Cooper, Helen

2008-01-01

Background Protein phosphatase 1 (PP1) is involved in diverse cellular processes, and is targeted to substrates via interaction with many different protein binding partners. PP1 catalytic subunits (PP1c) fall into PP1α and PP1β subfamilies based on sequence analysis, however very few PP1c binding proteins have been demonstrated to discriminate between PP1α and PP1β. Results URI (unconventional prefoldin RPB5 interactor) is a conserved molecular chaperone implicated in a variety of cellular processes, including the transcriptional response to nutrient signalling and maintenance of DNA integrity. We show that Drosophila Uri binds PP1α with much higher affinity than PP1β, and that this ability to discriminate between PP1c forms is conserved to humans. Most Uri is cytoplasmic, however we found some protein associated with active RNAPII on chromatin. We generated a uri loss of function allele, and show that uri is essential for viability in Drosophila. uri mutants have transcriptional defects, reduced cell viability and differentiation in the germline, and accumulate DNA damage in their nuclei. Conclusion Uri is the first PP1α specific binding protein to be described in Drosophila. Uri protein plays a role in transcriptional regulation. Activity of uri is required to maintain DNA integrity and cell survival in normal development. PMID:18412953

Peripheral hearing loss reduces the ability of children to direct selective attention during multi-talker listening.

PubMed

Holmes, Emma; Kitterick, Padraig T; Summerfield, A Quentin

2017-07-01

Restoring normal hearing requires knowledge of how peripheral and central auditory processes are affected by hearing loss. Previous research has focussed primarily on peripheral changes following sensorineural hearing loss, whereas consequences for central auditory processing have received less attention. We examined the ability of hearing-impaired children to direct auditory attention to a voice of interest (based on the talker's spatial location or gender) in the presence of a common form of background noise: the voices of competing talkers (i.e. during multi-talker, or "Cocktail Party" listening). We measured brain activity using electro-encephalography (EEG) when children prepared to direct attention to the spatial location or gender of an upcoming target talker who spoke in a mixture of three talkers. Compared to normally-hearing children, hearing-impaired children showed significantly less evidence of preparatory brain activity when required to direct spatial attention. This finding is consistent with the idea that hearing-impaired children have a reduced ability to prepare spatial attention for an upcoming talker. Moreover, preparatory brain activity was not restored when hearing-impaired children listened with their acoustic hearing aids. An implication of these findings is that steps to improve auditory attention alongside acoustic hearing aids may be required to improve the ability of hearing-impaired children to understand speech in the presence of competing talkers. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of combined physical education and nutritional programs on schoolchildren's healthy habits.

PubMed

Gallotta, Maria Chiara; Iazzoni, Sara; Emerenziani, Gian Pietro; Meucci, Marco; Migliaccio, Silvia; Guidetti, Laura; Baldari, Carlo

2016-01-01

Background. A multidisciplinary approach seems to be effective in creating healthy habits in children. The aim of this study was to evaluate the efficacy of three 5-month combined physical education (PE) and nutritional interventions on body composition, physical activity (PA) level, sedentary time and eating habits of schoolchildren. Methods. Anthropometric data, weekly PA level, sedentary time and eating habits of 230 healthy students were analysed using a repeated-measures ANOVA with Group (experimental group 1 vs experimental group 2 vs control group), Adiposity Status (under fat vs normal fat vs obese), and Time (pre vs post) as factors. Results. Body fat mass percentage increased after intervention (18.92 ± 8.61% vs 19.40 ± 8.51%) in all groups. The weekly PA level significantly increased after intervention in both experimental groups. Sedentary time significantly decreased after the intervention period (565.70 ± 252.93 vs 492.10 ± 230.97 min/week, p < 0.0001). Moreover, obese children were more sedentary than under fat and normal fat children. Children significantly changed the consumption of some specific foods after intervention. Discussion. This study revealed the effectiveness of a combined PE and nutritional intervention to improve children's healthful dietary practices and to encourage an active lifestyle. However, it needs a further appropriate development to establish patterns of healthful dietary practices that encourage an active lifestyle with which to maintain healthy habits through life.

A limit to the X-ray luminosity of nearby normal galaxies

NASA Technical Reports Server (NTRS)

Worrall, D. M.; Marshall, F. E.; Boldt, E. A.

1979-01-01

Emission is studied at luminosities lower than those for which individual discrete sources can be studied. It is shown that normal galaxies do not appear to provide the numerous low luminosity X-ray sources which could make up the 2-60 keV diffuse background. Indeed, upper limits suggest luminosities comparable with, or a little less than, that of the galaxy. This is consistent with the fact that the average optical luminosity of the sample galaxies within approximately 20 Mpc is slightly lower than that of the galaxy. An upper limit of approximately 1% of the diffuse background from such sources is derived.

Association between parenting practices and children's dietary intake, activity behavior and development of body mass index: the KOALA Birth Cohort Study.

PubMed

Gubbels, Jessica S; Kremers, Stef P J; Stafleu, Annette; de Vries, Sanne I; Goldbohm, R Alexandra; Dagnelie, Pieter C; de Vries, Nanne K; van Buuren, Stef; Thijs, Carel

2011-03-14

Insights into the effects of energy balance-related parenting practices on children's diet and activity behavior at an early age is warranted to determine which practices should be recommended and to whom. The purpose of this study was to examine child and parent background correlates of energy balance-related parenting practices at age 5, as well as the associations of these practices with children's diet, activity behavior, and body mass index (BMI) development. Questionnaire data originated from the KOALA Birth Cohort Study for ages 5 (N = 2026) and 7 (N = 1819). Linear regression analyses were used to examine the association of child and parent background characteristics with parenting practices (i.e., diet- and activity-related restriction, monitoring and stimulation), and to examine the associations between these parenting practices and children's diet (in terms of energy intake, dietary fiber intake, and added sugar intake) and activity behavior (i.e., physical activity and sedentary time) at age 5, as well as BMI development from age 5 to age 7. Moderation analyses were used to examine whether the associations between the parenting practices and child behavior depended on child characteristics. Several child and parent background characteristics were associated with the parenting practices. Dietary monitoring, stimulation of healthy intake and stimulation of physical activity were associated with desirable energy balance-related behaviors (i.e., dietary intake and/or activity behavior) and desirable BMI development, whereas restriction of sedentary time showed associations with undesirable behaviors and BMI development. Child eating style and weight status, but not child gender or activity style, moderated the associations between parenting practices and behavior. Dietary restriction and monitoring showed weaker, or even undesirable associations for children with a deviant eating style, whereas these practices showed associations with desirable behavior for normal eaters. By contrast, stimulation to eat healthy worked particularly well for children with a deviant eating style or a high BMI. Although most energy balance-related parenting practices were associated with desirable behaviors, some practices showed associations with undesirable child behavior and weight outcomes. Only parental stimulation showed desirable associations with regard to both diet and activity behavior. The interaction between parenting and child characteristics in the association with behavior calls for parenting that is tailored to the individual child.

Growth of L-band scintillation at anomaly crest station in association with strong TEC gradient: A study covering wide solar activity period

NASA Astrophysics Data System (ADS)

Pathak, K.; Devi, M.; Barbara, A. K.; Zahan, Y.

2018-01-01

The paper aims at to study the sources associated with growth of L band scintillation over Guwahati, an Appleton anomaly region. Starting with the analysis of diurnal and seasonal characteristic features of scintillation from a minimum sunspot number (Rz) of 10 to a maximum of 140, the paper shows that scintillations are more likely to develop during high solar activity period. It also highlights the explosive increase in occurrence of scintillation from post sunset to pre midnight hours in vernal equinoctial months when the background TEC is 50% more than on a normal day, accompanied by enhanced TEC decay rate. The role of equatorial anomaly effects through EXB drift processes are brought into discussion as possible sources on the growth of small scale irregularities leading to such scintillations.

Growth of L-band scintillation at anomaly crest station in association with strong TEC gradient: A study covering wide solar activity period

NASA Astrophysics Data System (ADS)

Pathak, K.; Devi, M.; Barbara, A. K.; Zahan, Y.

2018-07-01

The paper aims at to study the sources associated with growth of L band scintillation over Guwahati, an Appleton anomaly region. Starting with the analysis of diurnal and seasonal characteristic features of scintillation from a minimum sunspot number (Rz) of 10 to a maximum of 140, the paper shows that scintillations are more likely to develop during high solar activity period. It also highlights the explosive increase in occurrence of scintillation from post sunset to pre midnight hours in vernal equinoctial months when the background TEC is 50% more than on a normal day, accompanied by enhanced TEC decay rate. The role of equatorial anomaly effects through EXB drift processes are brought into discussion as possible sources on the growth of small scale irregularities leading to such scintillations.

Radon progeny in hydrometeors at the earth's surface.

PubMed

Voltaggio, M

2012-07-01

During atmospheric thermal inversions, dew and hoarfrost concentrate gamma emitting radionuclides of the short-lived (222)Rn progeny ((214)Pb and (214)Bi), causing an increase in the total natural gamma background from the ground. To highlight this phenomenon, a volcanic zone of high (222)Rn flux was studied during the winter season 2010-11. High-specific short-lived radon progeny activities up to 122 Bq g(-1) were detected in hydrometeors forming at the earth's surface (ESHs), corresponding to a mean increase of up to 17 % of the normal gamma background value. A theoretical model, depending on radon flux from soil and predicting the radon progeny concentrations in hydrometeors forming at the ESHs is presented. The comparison between model and field data shows a good correspondence. Around nuclear power plants or in nuclear facilities that use automatic NaI or CsI total gamma spectroscopy systems for monitoring radioactive contamination, hydrometeors forming at the ESHs in sites with a high radon flux could represent a relevant source of false alarms of radioactive contamination.

E2F transcription factor-1 deficiency reduces pathophysiology in the mouse model of Duchenne muscular dystrophy through increased muscle oxidative metabolism.

PubMed

Blanchet, Emilie; Annicotte, Jean-Sébastien; Pradelli, Ludivine A; Hugon, Gérald; Matecki, Stéfan; Mornet, Dominique; Rivier, François; Fajas, Lluis

2012-09-01

E2F1 deletion leads to increased mitochondrial number and function, increased body temperature in response to cold and increased resistance to fatigue with exercise. Since E2f1-/- mice show increased muscle performance, we examined the effect of E2f1 genetic inactivation in the mdx background, a mouse model of Duchenne muscular dystrophy (DMD). E2f1-/-;mdx mice demonstrated a strong reduction of physiopathological signs of DMD, including preservation of muscle structure, decreased inflammatory profile, increased utrophin expression, resulting in better endurance and muscle contractile parameters, comparable to normal mdx mice. E2f1 deficiency in the mdx genetic background increased the oxidative metabolic gene program, mitochondrial activity and improved muscle functions. Interestingly, we observed increased E2F1 protein levels in DMD patients, suggesting that E2F1 might represent a promising target for the treatment of DMD.

No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheehan, Daniel M.

2006-01-15

We tested the hypothesis that no threshold exists when estradiol acts through the same mechanism as an active endogenous estrogen. A Michaelis-Menten (MM) equation accounting for response saturation, background effects, and endogenous estrogen level fit a turtle sex-reversal data set with no threshold and estimated the endogenous dose. Additionally, 31 diverse literature dose-response data sets were analyzed by adding a term for nonhormonal background; good fits were obtained but endogenous dose estimations were not significant due to low resolving power. No thresholds were observed. Data sets were plotted using a normalized MM equation; all 178 data points were accommodated onmore » a single graph. Response rates from {approx}1% to >95% were well fit. The findings contradict the threshold assumption and low-dose safety. Calculating risk and assuming additivity of effects from multiple chemicals acting through the same mechanism rather than assuming a safe dose for nonthresholded curves is appropriate.« less

Review of approaches to the recording of background lesions in toxicologic pathology studies in rats.

PubMed

McInnes, E F; Scudamore, C L

2014-08-17

Pathological evaluation of lesions caused directly by xenobiotic treatment must always take into account the recognition of background (incidental) findings. Background lesions can be congenital or hereditary, histological variations, changes related to trauma or normal aging and physiologic or hormonal changes. This review focuses on the importance and correct approach to recording of background changes and includes discussion on sources of variability in background changes, the correct use of terminology, the concept of thresholds, historical control data, diagnostic drift, blind reading of slides, scoring and artifacts. The review is illustrated with background lesions in Sprague Dawley and Wistar rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

RELATIONSHIP OF PSYCHOTICISM WITH CERTAIN SOCIO-ECONOMIC VARIABLES1

PubMed Central

Arora, Manju Mehta (nee); Varma, V.K.

1982-01-01

SUMMARY A psychoticism questionnaire developed by the authors (Arora & Varma, 1980 a, b) was administered to 100 psychotics, 100 neurotics, 100 relatives of psychotics, and 100 normals. Relationship of P-score with six socioeconomic variables, i.e., age, sex, education, occupation, religion and urban, rural background was studied. P-score was found to be higher in younger age group (15-24 years) in each of the four clinical groups but was significantly low in psychoitics and their relatives. No sex differences were observed regarding P-score. Significant inverse relationship between P-score and education and occupational status was found only for the normal groups. No significant difference was seen in psychoticism score between the two religious groups—Hindus and Sikhs. Those from rural background had higher P-score as compared to those from urban background, but the differences did not reach statistical significance. PMID:21965906

GSCALite: A Web Server for Gene Set Cancer Analysis.

PubMed

Liu, Chun-Jie; Hu, Fei-Fei; Xia, Mengxuan; Han, Leng; Zhang, Qiong; Guo, An-Yuan

2018-05-22

The availability of cancer genomic data makes it possible to analyze genes related to cancer. Cancer is usually the result of a set of genes and the signal of a single gene could be covered by background noise. Here, we present a web server named Gene Set Cancer Analysis (GSCALite) to analyze a set of genes in cancers with the following functional modules. (i) Differential expression in tumor vs normal, and the survival analysis; (ii) Genomic variations and their survival analysis; (iii) Gene expression associated cancer pathway activity; (iv) miRNA regulatory network for genes; (v) Drug sensitivity for genes; (vi) Normal tissue expression and eQTL for genes. GSCALite is a user-friendly web server for dynamic analysis and visualization of gene set in cancer and drug sensitivity correlation, which will be of broad utilities to cancer researchers. GSCALite is available on http://bioinfo.life.hust.edu.cn/web/GSCALite/. guoay@hust.edu.cn or zhangqiong@hust.edu.cn. Supplementary data are available at Bioinformatics online.

The Neurotensin Receptor-1 Pathway Contributes to Human Ductal Breast Cancer Progression

PubMed Central

Dupouy, Sandra; Viardot-Foucault, Véronique; Alifano, Marco; Souazé, Frédérique; Plu-Bureau, Geneviève; Chaouat, Marc; Lavaur, Anne; Hugol, Danielle; Gespach, Christian

2009-01-01

Background The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. Methods and Results we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. Conclusion these data support the activation of neurotensinergic deleterious pathways in breast cancer progression. PMID:19156213

Olfactory behavior and physiology are disrupted in prion protein knockout mice.

PubMed

Le Pichon, Claire E; Valley, Matthew T; Polymenidou, Magdalini; Chesler, Alexander T; Sagdullaev, Botir T; Aguzzi, Adriano; Firestein, Stuart

2009-01-01

The prion protein PrP(C) is infamous for its role in disease, but its normal physiological function remains unknown. Here we found a previously unknown behavioral phenotype of Prnp(-/-) mice in an odor-guided task. This phenotype was manifest in three Prnp knockout lines on different genetic backgrounds, which provides strong evidence that the phenotype is caused by a lack of PrP(C) rather than by other genetic factors. Prnp(-/-) mice also showed altered behavior in a second olfactory task, suggesting that the phenotype is olfactory specific. Furthermore, PrP(C) deficiency affected oscillatory activity in the deep layers of the main olfactory bulb, as well as dendrodendritic synaptic transmission between olfactory bulb granule and mitral cells. Notably, both the behavioral and electrophysiological alterations found in Prnp(-/-) mice were rescued by transgenic neuronal-specific expression of PrP(C). These data suggest that PrP(C) is important in the normal processing of sensory information by the olfactory system.

Synthetic Microwave Imaging Reflectometry diagnostic using 3D FDTD Simulations

NASA Astrophysics Data System (ADS)

Kruger, Scott; Jenkins, Thomas; Smithe, David; King, Jacob; Nimrod Team Team

2017-10-01

Microwave Imaging Reflectometry (MIR) has become a standard diagnostic for understanding tokamak edge perturbations, including the edge harmonic oscillations in QH mode operation. These long-wavelength perturbations are larger than the normal turbulent fluctuation levels and thus normal analysis of synthetic signals become more difficult. To investigate, we construct a synthetic MIR diagnostic for exploring density fluctuation amplitudes in the tokamak plasma edge by using the three-dimensional, full-wave FDTD code Vorpal. The source microwave beam for the diagnostic is generated and refelected at the cutoff surface that is distorted by 2D density fluctuations in the edge plasma. Synthetic imaging optics at the detector can be used to understand the fluctuation and background density profiles. We apply the diagnostic to understand the fluctuations in edge plasma density during QH-mode activity in the DIII-D tokamak, as modeled by the NIMROD code. This work was funded under DOE Grant Number DE-FC02-08ER54972.

Effects of a primordial magnetic field with log-normal distribution on the cosmic microwave background

NASA Astrophysics Data System (ADS)

Yamazaki, Dai G.; Ichiki, Kiyotomo; Takahashi, Keitaro

2011-12-01

We study the effect of primordial magnetic fields (PMFs) on the anisotropies of the cosmic microwave background (CMB). We assume the spectrum of PMFs is described by log-normal distribution which has a characteristic scale, rather than power-law spectrum. This scale is expected to reflect the generation mechanisms and our analysis is complementary to previous studies with power-law spectrum. We calculate power spectra of energy density and Lorentz force of the log-normal PMFs, and then calculate CMB temperature and polarization angular power spectra from scalar, vector, and tensor modes of perturbations generated from such PMFs. By comparing these spectra with WMAP7, QUaD, CBI, Boomerang, and ACBAR data sets, we find that the current CMB data set places the strongest constraint at k≃10-2.5Mpc-1 with the upper limit B≲3nG.

Where they live, how they play: Neighborhood greenness and outdoor physical activity among preschoolers

PubMed Central

2011-01-01

Background Emerging empirical evidence suggests exposure to "green" environments may encourage higher levels of physical activity among children. Few studies, however, have explored this association exclusively in pre-school aged children in the United States. We examined whether residing in neighborhoods with higher levels of greenness was associated with higher levels of outdoor physical activity among preschoolers. In addition, we also explored whether outdoor playing behaviors (e.g., active vs. quiet) were influenced by levels of neighborhood greenness independent of demographic and parental support factors. Results Higher levels of neighborhood greenness as measured by the Normalized Difference Vegetation Index (NDVI) was associated with higher levels of outdoor playing time among preschool-aged children in our sample. Specifically, a one unit increase in neighborhood greenness increased a child's outdoor playing time by approximately 3 minutes. A dose-response relationship was observed between increasing levels of parental support for physical activity (e.g., time spent playing with children) and child outdoor physical activity (p < 0.01). Conclusions Consistent with previous studies, neighborhood greenness influences physical activity behavior. However, for preschoolers, parental involvement may be more critical for improving physical activity levels. PMID:22165919

Distribution and function of the peptide transporter PEPT2 in normal and cystic fibrosis human lung

PubMed Central

Groneberg, D; Eynott, P; Doring, F; Thai, D; Oates, T; Barnes, P; Chung, K; Daniel, H; Fischer, A

2002-01-01

Background: Aerosol administration of peptide based drugs has an important role in the treatment of various pulmonary and systemic diseases. The characterisation of pulmonary peptide transport pathways can lead to new strategies in aerosol drug treatment. Methods: Immunohistochemistry and ex vivo uptake studies were established to assess the distribution and activity of the ß-lactam transporting high affinity proton coupled peptide transporter PEPT2 in normal and cystic fibrosis human airway tissue. Results: PEPT2 immunoreactivity in normal human airways was localised to cells of the tracheal and bronchial epithelium and the endothelium of small vessels. In peripheral lung immunoreactivity was restricted to type II pneumocytes. In sections of cystic fibrosis lung a similar pattern of distribution was obtained with signals localised to endothelial cells, airway epithelium, and type II pneumocytes. Functional ex vivo uptake studies with fresh lung specimens led to an uptake of the fluorophore conjugated dipeptide derivative D-Ala-L-Lys-AMCA into bronchial epithelial cells and type II pneumocytes. This uptake was competitively inhibited by dipeptides and cephalosporins but not ACE inhibitors, indicating a substrate specificity as described for PEPT2. Conclusions: These findings provide evidence for the expression and function of the peptide transporter PEPT2 in the normal and cystic fibrosis human respiratory tract and suggest that PEPT2 is likely to play a role in the transport of pulmonary peptides and peptidomimetics. PMID:11809991

The Small GTPase Rif Is Dispensable for Platelet Filopodia Generation in Mice

PubMed Central

Goggs, Robert; Savage, Joshua S.; Mellor, Harry; Poole, Alastair W.

2013-01-01

Background Formation of filopodia and other shape change events are vital for platelet hemostatic function. The mechanisms regulating filopodia formation by platelets are incompletely understood however. In particular the small GTPase responsible for initiating filopodia formation by platelets remains elusive. The canonical pathway involving Cdc42 is not essential for filopodia formation in mouse platelets. The small GTPase Rif (RhoF) provides an alternative route to filopodia generation in other cell types and is expressed in both human and mouse platelets. Hypothesis/Objective We hypothesized that Rif might be responsible for generating filopodia by platelets and generated a novel knockout mouse model to investigate the functional role of Rif in platelets. Methodology/Principal Findings Constitutive RhoF−/− mice are viable and have normal platelet, leukocyte and erythrocyte counts and indices. RhoF−/− platelets form filopodia and spread normally on various agonist surfaces in static conditions and under arterial shear. In addition, RhoF−/− platelets have normal actin dynamics, are able to activate and aggregate normally and secrete from alpha and dense granules in response to collagen related peptide and thrombin stimulation. Conclusions The small GTPase Rif does not appear to be critical for platelet function in mice. Functional overlap between Rif and other small GTPases may be responsible for the non-essential role of Rif in platelets. PMID:23359340

Gecko proteins induce the apoptosis of bladder cancer 5637 cells by inhibiting Akt and activating the intrinsic caspase cascade.

PubMed

Kim, Geun-Young; Park, Soon Yong; Jo, Ara; Kim, Mira; Leem, Sun-Hee; Jun, Woo-Jin; Shim, Sang In; Lee, Sang Chul; Chung, Jin Woong

2015-09-01

Gecko proteins have long been used as anti-tumor agents in oriental medicine, without any scientific background. Although anti-tumor effects of Gecko proteins on several cancers were recently reported, their effect on bladder cancer has not been investigated. Thus, we explored the anti-tumor effect of Gecko proteins and its cellular mechanisms in human bladder cancer 5637 cells. Gecko proteins significantly reduced the viability of 5637 cells without any cytotoxic effect on normal cells. These proteins increased the Annexin-V staining and the amount of condensed chromatin, demonstrating that the Gecko proteinsinduced cell death was caused by apoptosis. Gecko proteins suppressed Akt activation, and the overexpression of constitutively active form of myristoylated Akt prevented Gecko proteins-induced death of 5637 cells. Furthermore, Gecko proteins activated caspase 9 and caspase 3/7. Taken together, our data demonstrated that Gecko proteins suppressed the Akt pathway and activated the intrinsic caspase pathway, leading to the apoptosis of bladder cancer cells. [BMB Reports 2015; 48(9): 531-536].

46 CFR 113.50-15 - Loudspeakers.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... With the vessel underway in normal conditions, the minimum sound pressure levels for broadcasting emergency announcements must be— (1) In interior spaces, 75 dB(A) or, if the background noise level exceeds 75 dB(A), then at least 20 dB(A) above maximum background noise level; and (2) In exterior spaces, 80...

Reducing the background fluorescence in mice receiving fluorophore/inhibitor DNA duplexes.

PubMed

Liang, Minmin; Liu, Xinrong; Liu, Guozheng; Dou, Shuping; Cheng, Dengfeng; Liu, Yuxia; Rusckowski, Mary; Hnatowich, Donald J

2011-02-07

In principle, a DNA duplex consisting of an antisense fluorophore-conjugated major strand hybridized to a shorter complementary inhibitor-conjugated minor strand should provide fluorescence only in the tumor after intravenous administration if designed to remain intact except in the presence in tumor of its mRNA target. While we have obtained impressive tumor images in mice using this approach, there remains some background fluorescence. In this study, tissue homogenates of selected mouse organs were incubated with a test duplex and the kinetics of duplex dissociation in normal tissues were measured. In this manner we were able to identify the liver as the likely major source responsible for the duplex dissociation providing this fluorescence background. Thereafter liver homogenates were used to screen a series of duplex candidates with variable-length minor strands, and dissociation was measured by gel electrophoresis. The selected fluorophore/inhibitor duplex with improved stability displayed an insignificant (P > 0.05) background fluorescence after administration to SKH-1 normal mice and apparently without affecting target mRNA binding in vitro in cell culture or in vivo in tumor bearing mice.

Metabolomic analysis of longissimus from underperforming piglets relative to piglets with normal preweaning growth

USDA-ARS?s Scientific Manuscript database

Background: The increase in intra-litter variability in weaning weight during the past twenty years has increased production costs in all in/all out swine production. One contributor to this variability is the normal birth weight pig that grows at a slower rate than littermates of similar birth weig...

Right up There: Hemispatial and Hand Asymmetries of Altitudinal Pseudoneglect

ERIC Educational Resources Information Center

Suavansri, Ketchai; Falchook, Adam D.; Williamson, John B.; Heilman, Kenneth M.

2012-01-01

Background: Pseudoneglect is a normal left sided spatial bias observed with attempted bisections of horizontal lines and a normal upward bias observed with attempted bisections of vertical lines. Horizontal pseudoneglect has been attributed to right hemispheric dominance for the allocation of attention. The goal of this study was to test the…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Guang, E-mail: lig2@mskcc.org; Schmidtlein, C. Ross; Humm, John L.

Purpose: To assess and account for the impact of respiratory motion on the variability of activity and volume determination of liver tumor in positron emission tomography (PET) through a comparison between free-breathing (FB) and respiration-suspended (RS) PET images. Methods: As part of a PET/computed tomography (CT) guided percutaneous liver ablation procedure performed on a PET/CT scanner, a patient's breathing is suspended on a ventilator, allowing the acquisition of a near-motionless PET and CT reference images of the liver. In this study, baseline RS and FB PET/CT images of 20 patients undergoing thermal ablation were acquired. The RS PET provides near-motionlessmore » reference in a human study, and thereby allows a quantitative evaluation of the effect of respiratory motion on PET images obtained under FB conditions. Two methods were applied to calculate tumor activity and volume: (1) threshold-based segmentation (TBS), estimating the total lesion glycolysis (TLG) and the segmented volume and (2) histogram-based estimation (HBE), yielding the background-subtracted lesion (BSL) activity and associated volume. The TBS method employs 50% of the maximum standardized uptake value (SUV{sub max}) as the threshold for tumors with SUV{sub max} ≥ 2× SUV{sub liver-bkg}, and tumor activity above this threshold yields TLG{sub 50%}. The HBE method determines local PET background based on a Gaussian fit of the low SUV peak in a SUV-volume histogram, which is generated within a user-defined and optimized volume of interest containing both local background and lesion uptakes. Voxels with PET intensity above the fitted background were considered to have originated from the tumor and used to calculate the BSL activity and its associated lesion volume. Results: Respiratory motion caused SUV{sub max} to decrease from RS to FB by −15% ± 11% (p = 0.01). Using TBS method, there was also a decrease in SUV{sub mean} (−18% ± 9%, p = 0.01), but an increase in TLG{sub 50%} (18% ± 36%) and in the segmented volume (47% ± 52%, p = 0.01) from RS to FB PET images. The background uptake in normal liver was stable, 1% ± 9%. In contrast, using the HBE method, the differences in both BSL activity and BSL volume from RS to FB were −8% ± 10% (p = 0.005) and 0% ± 16% (p = 0.94), respectively. Conclusions: This is the first time that almost motion-free PET images of the human liver were acquired and compared to free-breathing PET. The BSL method's results are more consistent, for the calculation of both tumor activity and volume in RS and FB PET images, than those using conventional TBS. This suggests that the BSL method might be less sensitive to motion blurring and provides an improved estimation of tumor activity and volume in the presence of respiratory motion.« less

Anxiety sensitivity and auditory perception of heartbeat.

PubMed

Pollock, R A; Carter, A S; Amir, N; Marks, L E

2006-12-01

Anxiety sensitivity (AS) is the fear of sensations associated with autonomic arousal. AS has been associated with the development and maintenance of panic disorder. Given that panic patients often rate cardiac symptoms as the most fear-provoking feature of a panic attack, AS individuals may be especially responsive to cardiac stimuli. Consequently, we developed a signal-in-white-noise detection paradigm to examine the strategies that high and low AS individuals use to detect and discriminate normal and abnormal heartbeat sounds. Compared to low AS individuals, high AS individuals demonstrated a greater propensity to report the presence of normal, but not abnormal, heartbeat sounds. High and low AS individuals did not differ in their ability to perceive normal heartbeat sounds against a background of white noise; however, high AS individuals consistently demonstrated lower ability to discriminate abnormal heartbeats from background noise and between abnormal and normal heartbeats. AS was characterized by an elevated false alarm rate across all tasks. These results suggest that heartbeat sounds may be fear-relevant cues for AS individuals, and may affect their attention and perception in tasks involving threat signals.

Longitudinal Relationships between Caloric Expenditure and Gray Matter in the Cardiovascular Health Study

PubMed Central

Raji, Cyrus A.; Merrill, David A.; Eyre, Harris; Mallam, Sravya; Torosyan, Nare; Erickson, Kirk I.; Lopez, Oscar L.; Becker, James T.; Carmichael, Owen T.; Gach, H. Michael; Thompson, Paul M.; Longstreth, W.T.; Kuller, Lewis H.

2016-01-01

Background: Physical activity (PA) can be neuroprotective and reduce the risk for Alzheimer’s disease (AD). In assessing physical activity, caloric expenditure is a proxy marker reflecting the sum total of multiple physical activity types conducted by an individual. Objective:To assess caloric expenditure, as a proxy marker of PA, as a predictive measure of gray matter (GM) volumes in the normal and cognitively impaired elderly persons. Methods: All subjects in this study were recruited from the Institutional Review Board approved Cardiovascular Health Study (CHS), a multisite population-based longitudinal study in persons aged 65 and older. We analyzed a sub-sample of CHS participants 876 subjects (mean age 78.3, 57.5% F, 42.5% M) who had i) energy output assessed as kilocalories (kcal) per week using the standardized Minnesota Leisure-Time Activities questionnaire, ii) cognitive assessments for clinical classification of normal cognition, mild cognitive impairment (MCI), and AD, and iii) volumetric MR imaging of the brain. Voxel-based morphometry modeled the relationship between kcal/week and GM volumes while accounting for standard covariates including head size, age, sex, white matter hyperintensity lesions, MCI or AD status, and site. Multiple comparisons were controlled using a False Discovery Rate of 5 percent. Results: Higher energy output, from a variety of physical activity types, was associated with larger GM volumes in frontal, temporal, and parietal lobes, as well as hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis. Conclusion:Increasing energy output from a variety of physical activities is related to larger gray matter volumes in the elderly, regardless of cognitive status. PMID:26967227

Effect of a prenatal lifestyle intervention on physical activity level in late pregnancy and the first year postpartum

PubMed Central

Sagedal, Linda Reme; Haakstad, Lene Annette Hagen; Lohne-Seiler, Hilde

2017-01-01

Background Despite documented health benefits for mother and baby, physical activity (PA)-level tends to decline in pregnancy. Overweight/obese and physically inactive women are two selected groups at increased risk of pregnancy complications. Thus, efficient strategies to maintain or increase PA-level in pregnancy and the postpartum period, especially among these women, are warranted. This secondary analysis examined the effect of a prenatal lifestyle-intervention on PA-level in late pregnancy and the first year postpartum, with subanalysis on initially physically active versus inactive and normal-weight versus overweight/obese women. Method The Norwegian Fit for Delivery (NFFD) randomized controlled trial included healthy primiparous women with singleton pregnancies and body mass index (BMI) ≥19 kg/m2 assigned to an intervention group, n = 303 (twice weekly group-exercises and dietary counseling) or a control group, n = 303 (standard prenatal care). The International Physical Activity Questionnaire short-form was used to assess PA-levels at inclusion (mean gestational week (GW) 16), GW 36, and six and 12 months postpartum. Results At GW 36, a positive intervention-effect with a significant between-group difference in total PA-level compared to time of inclusion was found for the total group (530 MET-min/week, p = 0.001) and the subgroups of normal-weight (533 MET-min/week, p = 0.003) and initially active women (717 MET-min/week, p<0.001). Intervention-effect was dependent on exercise-adherence among overweight/obese and inactive women. Compared to time of inclusion, the intervention groups maintained total PA-level at GW 36, while total PA-level decreased in the control groups. The PA-levels increased postpartum, but with no significant differences between the randomization groups. Conclusion The NFFD prenatal combined lifestyle intervention had a significant effect on TPA-level in late pregnancy among women entering pregnancy normal-weight or physically active, thereby preventing the downward trend typically seen during pregnancy. Intervention-effect among overweight/obese and physically inactive women was, however, dependent on exercise-adherence. Long-term intervention-effect was not observed in the postpartum period. PMID:29176762

Biological Effects of a De Novo Designed Myxoma Virus Peptide Analogue: Evaluation of Cytotoxicity on Tumor Cells

PubMed Central

Istivan, Taghrid S.; Pirogova, Elena; Gan, Emily; Almansour, Nahlah M.; Coloe, Peter J.; Cosic, Irena

2011-01-01

Background The Resonant Recognition Model (RRM) is a physico-mathematical model that interprets protein sequence linear information using digital signal processing methods. In this study the RRM concept was employed for structure-function analysis of myxoma virus (MV) proteins and the design of a short bioactive therapeutic peptide with MV-like antitumor/cytotoxic activity. Methodology/Principal Findings The analogue RRM-MV was designed by RRM as a linear 18 aa 2.3 kDa peptide. The biological activity of this computationally designed peptide analogue against cancer and normal cell lines was investigated. The cellular cytotoxicity effects were confirmed by confocal immunofluorescence microscopy, by measuring the levels of cytoplasmic lactate dehydrogenase (LDH) and by Prestoblue cell viability assay for up to 72 hours in peptide treated and non-treated cell cultures. Our results revealed that RRM-MV induced a significant dose and time-dependent cytotoxic effect on murine and human cancer cell lines. Yet, when normal murine cell lines were similarly treated with RRM-MV, no cytotoxic effects were observed. Furthermore, the non-bioactive RRM designed peptide RRM-C produced negligible cytotoxic effects on these cancer and normal cell lines when used at similar concentrations. The presence/absence of phosphorylated Akt activity in B16F0 mouse melanoma cells was assessed to indicate the possible apoptosis signalling pathway that could be affected by the peptide treatment. So far, Akt activity did not seem to be significantly affected by RRM-MV as is the case for the original viral protein. Conclusions/Significance Our findings indicate the successful application of the RRM concept to design a bioactive peptide analogue (RRM-MV) with cytotoxic effects on tumor cells only. This 2.345 kDa peptide analogue to a 49 kDa viral protein may be suitable to be developed as a potential cancer therapeutic. These results also open a new direction to the rational design of therapeutic agents for future cancer treatment. PMID:21949758

Phasic Contractions of the Mouse Vagina and Cervix at Different Phases of the Estrus Cycle and during Late Pregnancy

PubMed Central

Gravina, Fernanda S.; van Helden, Dirk F.; Kerr, Karen P.; de Oliveira, Ramatis B.; Jobling, Phillip

2014-01-01

Background/Aims The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking. Methodology/Principal Findings Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina. Conclusions/Significance Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges. PMID:25337931

Memory performance on the Auditory Inference Span Test is independent of background noise type for young adults with normal hearing at high speech intelligibility

PubMed Central

Rönnberg, Niklas; Rudner, Mary; Lunner, Thomas; Stenfelt, Stefan

2014-01-01

Listening in noise is often perceived to be effortful. This is partly because cognitive resources are engaged in separating the target signal from background noise, leaving fewer resources for storage and processing of the content of the message in working memory. The Auditory Inference Span Test (AIST) is designed to assess listening effort by measuring the ability to maintain and process heard information. The aim of this study was to use AIST to investigate the effect of background noise types and signal-to-noise ratio (SNR) on listening effort, as a function of working memory capacity (WMC) and updating ability (UA). The AIST was administered in three types of background noise: steady-state speech-shaped noise, amplitude modulated speech-shaped noise, and unintelligible speech. Three SNRs targeting 90% speech intelligibility or better were used in each of the three noise types, giving nine different conditions. The reading span test assessed WMC, while UA was assessed with the letter memory test. Twenty young adults with normal hearing participated in the study. Results showed that AIST performance was not influenced by noise type at the same intelligibility level, but became worse with worse SNR when background noise was speech-like. Performance on AIST also decreased with increasing memory load level. Correlations between AIST performance and the cognitive measurements suggested that WMC is of more importance for listening when SNRs are worse, while UA is of more importance for listening in easier SNRs. The results indicated that in young adults with normal hearing, the effort involved in listening in noise at high intelligibility levels is independent of the noise type. However, when noise is speech-like and intelligibility decreases, listening effort increases, probably due to extra demands on cognitive resources added by the informational masking created by the speech fragments and vocal sounds in the background noise. PMID:25566159

Memory performance on the Auditory Inference Span Test is independent of background noise type for young adults with normal hearing at high speech intelligibility.

PubMed

Rönnberg, Niklas; Rudner, Mary; Lunner, Thomas; Stenfelt, Stefan

2014-01-01

Listening in noise is often perceived to be effortful. This is partly because cognitive resources are engaged in separating the target signal from background noise, leaving fewer resources for storage and processing of the content of the message in working memory. The Auditory Inference Span Test (AIST) is designed to assess listening effort by measuring the ability to maintain and process heard information. The aim of this study was to use AIST to investigate the effect of background noise types and signal-to-noise ratio (SNR) on listening effort, as a function of working memory capacity (WMC) and updating ability (UA). The AIST was administered in three types of background noise: steady-state speech-shaped noise, amplitude modulated speech-shaped noise, and unintelligible speech. Three SNRs targeting 90% speech intelligibility or better were used in each of the three noise types, giving nine different conditions. The reading span test assessed WMC, while UA was assessed with the letter memory test. Twenty young adults with normal hearing participated in the study. Results showed that AIST performance was not influenced by noise type at the same intelligibility level, but became worse with worse SNR when background noise was speech-like. Performance on AIST also decreased with increasing memory load level. Correlations between AIST performance and the cognitive measurements suggested that WMC is of more importance for listening when SNRs are worse, while UA is of more importance for listening in easier SNRs. The results indicated that in young adults with normal hearing, the effort involved in listening in noise at high intelligibility levels is independent of the noise type. However, when noise is speech-like and intelligibility decreases, listening effort increases, probably due to extra demands on cognitive resources added by the informational masking created by the speech fragments and vocal sounds in the background noise.

Assessment of toxic metal contamination using a regional lithogenic geochemical background, Pampean area river basin, Argentina.

PubMed

Castro, Liliana Norma; Rendina, Alicia Elena; Orgeira, Maria Julia

2018-06-15

Contamination assessment in riverbed sediments depends on the accurate determination of the background values. The aim of this study is to assess the degree of contamination and to evaluate the most adequate background for the determination of anthropogenic contamination in Cd, Cr, Cu, Ni, Pb and Zn in bed sediments of the Pampean area river basin (Matanza-Riachuelo River and tributary streams), Argentina. The geo-accumulation index (Igeo) values were calculated using selected lithogenic backgrounds (loess, loessoid sediments and paleosoils), the metal concentrations in the residual fraction (F4) in riverbed sediments and a global average shale often applied in the estimation of toxic metal Igeo. The IgeoF4, IgeoLZB and most of the others Igeos, indicated that in land areas used mainly for agriculture and cattle grazing, the superficial sediments were uncontaminated with Cd, Cr, Cu and Zn, and slightly contaminated with Ni and Pb. Conversely, in those areas dedicated to urban and industrial use, the metal contamination was greater. Overall, the relatively significant anthropogenic contamination of Cr > Pb ≥ Cu > Zn > Ni > Cd in the Riachuelo River area was associated with metallurgic activities, tanning and industrial waste. The comparative analysis of different values suggested that Buenos Aires' "pristine" loess could be recommended to evaluate the Igeo index of riverbed sediments in the Pampean area. To enhance the use of the selected background, the normalized enrichment factor using Al. In this study case, the Igeo and the EF using LZB background display the same trend, showing the greatest degree of contamination, as would be expected, in Riachuelo samples (RIA 1 and RIA 2) located in the urban/industrial area. Copyright © 2018 Elsevier B.V. All rights reserved.

Prevalence and etiology of false normal aEEG recordings in neonatal hypoxic-ischaemic encephalopathy

PubMed Central

2013-01-01

Background Amplitude-integrated electroencephalography (aEEG) is a useful tool to determine the severity of neonatal hypoxic-ischemic encephalopathy (HIE). Our aim was to assess the prevalence and study the origin of false normal aEEG recordings based on 85 aEEG recordings registered before six hours of age. Methods Raw EEG recordings were reevaluated retrospectively with Fourier analysis to identify and describe the frequency patterns of the raw EEG signal, in cases with inconsistent aEEG recordings and clinical symptoms. Power spectral density curves, power (P) and median frequency (MF) were determined using the raw EEG. In 7 patients non-depolarizing muscle relaxant (NDMR) exposure was found. The EEG sections were analyzed and compared before and after NDMR administration. Results The reevaluation found that the aEEG was truly normal in 4 neonates. In 3 neonates, high voltage electrocardiographic (ECG) artifacts were found with flat trace on raw EEG. High frequency component (HFC) was found as a cause of normal appearing aEEG in 10 neonates. HFC disappeared while P and MF decreased significantly upon NDMR administration in each observed case. Conclusion Occurrence of false normal aEEG background pattern is relatively high in neonates with HIE and hypothermia. High frequency EEG artifacts suggestive of shivering were found to be the most common cause of false normal aEEG in hypothermic neonates while high voltage ECG artifacts are less common. PMID:24268061

Raman background photobleaching as a possible method of cancer diagnostics

NASA Astrophysics Data System (ADS)

Brandt, Nikolai N.; Brandt, Nikolai B.; Chikishev, Andrey Y.; Gangardt, Mihail G.; Karyakina, Nina F.

2001-06-01

Kinetics of photobleaching of background in Raman spectra of aqueous solutions of plant toxins ricin and ricin agglutinin, ricin binding subunit, and normal and malignant human blood serum were measured. For the excitation of the spectra cw and pulsed laser radiation were used. The spectra of Raman background change upon laser irradiation. Background intensity is lower for the samples with small molecular weight. The cyclization of amino acid residues in the toxin molecules as well as in human blood serum can be a reason of the Raman background. The model of the background photobleaching is proposed. The differences in photobleaching kinetics in the cases of cw and pulsed laser radiation are discussed. It is shown that Raman background photobleaching can be very informative for cancer diagnostics.

Evaluation of Biological Activity of Mastic Extracts Based on Chemotherapeutic Indices

PubMed Central

SUZUKI, RYUICHIRO; SAKAGAMI, HIROSHI; AMANO, SHIGERU; FUKUCHI, KUNIHIKO; SUNAGA, KATSUYOSHI; KANAMOTO, TAISEI; TERAKUBO, SHIGEMI; NAKASHIMA, HIDEKI; SHIRATAKI, YOSHIAKI; TOMOMURA, MINEKO; MASUDA, YOSHIKO; YOKOSE, SATOSHI; TOMOMURA, AKITO; WATANABE, HIROFUMI; OKAWARA, MASAKI; MATAHIRA, YOSHIHARU

2017-01-01

Background: Most previous mastic investigators have not considered its potent cytotoxicity that may significantly affect the interpretation of obtained data. In the present study, we re-evaluated several biological activities of mastic extracts, based on chemotherapeutic indexes. Materials and Methods: Pulverized mastic gum was extracted with n-hexane and then with ethyl acetate or independently with methanol or n-butanol. Tumor specificity (TS) of the extracts was determined by their cytotoxicity against human malignant and non-malignant cells. Antibacterial activity was determined by their cytotoxicity against bacteria and normal oral cells. Antiviral activity was determined by their protection of viral infection and cytotoxic activity. Cytochrome P-450 (CYP) 3A4 activity was measured by β-hydroxylation of testosterone. Results: Ethyl acetate extract showed slightly higher tumor specificity (TS=2.6) and one order higher antibacterial activity (selectivity index (SI)=0.813) than other extracts (TS=1.4-2.5; SI=0.030-0.063). All extracts showed no anti-human immunodeficiency virus (HIV) activity, but some anti-herpes simplex virus (HSV) activity, which was masked by potent cytotoxicity. They showed strong inhibitory activity against CYP3A4. Conclusion: Ethyl acetate extraction following the removal of cytotoxic and CYP3A4 inhibitory substances by n-hexane can enhance antitumor and antibacterial activity of mastic. PMID:28652425

Phenobarbitone, neonatal seizures, and video-EEG

PubMed Central

Boylan, G; Rennie, J; Pressler, R; Wilson, G; Morton, M; Binnie, C

2002-01-01

Aims: To evaluate the effectiveness of phenobarbitone as an anticonvulsant in neonates. Methods: An observational study using video-EEG telemetry. Video-EEG was obtained before treatment was started, for an hour after treatment was given, two hours after treatment was given, and again between 12 and 24 hours after treatment was given. Patients were recruited from all babies who required phenobarbitone (20–40 mg/kg intravenously over 20 minutes) for suspected clinical seizures and had EEG monitoring one hour before and up to 24 hours after the initial dose. An EEG seizure discharge was defined as a sudden repetitive stereotyped discharge lasting for at least 10 seconds. Neonatal status epilepticus was defined as continuous seizure activity for at least 30 minutes. Seizures were categorised as EEG seizure discharges only (electrographic), or as EEG seizure discharges with accompanying clinical manifestations (electroclinical). Surviving babies were assessed at one year using the Griffiths neurodevelopmental score. Results: Fourteen babies were studied. Four responded to phenobarbitone; these had normal or moderately abnormal EEG background abnormalities and outcome was good. In the other 10 babies electrographic seizures increased after treatment, whereas electroclinical seizures reduced. Three babies were treated with second line anticonvulsants, of whom two responded. One of these had a normal neurodevelopmental score at one year, but the outcome for the remainder of the whole group was poor. Conclusion: Phenobarbitone is often ineffective as a first line anticonvulsant in neonates with seizures in whom the background EEG is significantly abnormal. PMID:11978746

Modeling the time-varying and level-dependent effects of the medial olivocochlear reflex in auditory nerve responses.

PubMed

Smalt, Christopher J; Heinz, Michael G; Strickland, Elizabeth A

2014-04-01

The medial olivocochlear reflex (MOCR) has been hypothesized to provide benefit for listening in noisy environments. This advantage can be attributed to a feedback mechanism that suppresses auditory nerve (AN) firing in continuous background noise, resulting in increased sensitivity to a tone or speech. MOC neurons synapse on outer hair cells (OHCs), and their activity effectively reduces cochlear gain. The computational model developed in this study implements the time-varying, characteristic frequency (CF) and level-dependent effects of the MOCR within the framework of a well-established model for normal and hearing-impaired AN responses. A second-order linear system was used to model the time-course of the MOCR using physiological data in humans. The stimulus-level-dependent parameters of the efferent pathway were estimated by fitting AN sensitivity derived from responses in decerebrate cats using a tone-in-noise paradigm. The resulting model uses a binaural, time-varying, CF-dependent, level-dependent OHC gain reduction for both ipsilateral and contralateral stimuli that improves detection of a tone in noise, similarly to recorded AN responses. The MOCR may be important for speech recognition in continuous background noise as well as for protection from acoustic trauma. Further study of this model and its efferent feedback loop may improve our understanding of the effects of sensorineural hearing loss in noisy situations, a condition in which hearing aids currently struggle to restore normal speech perception.

Increased Systemic Cytokine/Chemokine Expression in Asthmatic and Non-asthmatic Patients with Bacterial, Viral or Mixed Lung Infection.

PubMed

Giuffrida, M J; Valero, N; Mosquera, J; Duran, A; Arocha, F; Chacín, B; Espina, L M; Gotera, J; Bermudez, J; Mavarez, A; Alvarez-Mon, M

2017-04-01

This study was aimed to determine the profiles of serum cytokines (IL-1β, TNF-α, IL-4, IL-5) and chemokines (MCP-1: monocyte chemoattract protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in individuals with an asthmatic versus a non-asthmatic background with bacterial, viral or mixed acute respiratory infection. Asthmatic (n = 14) and non-asthmatic (n = 29) patients with acute viral, bacterial or mixed (bacterial and viruses) respiratory infection were studied. Patients were also analysed as individuals with pneumonia or bronchitis. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in serum was determined by ELISA. Increased cytokine/chemokine concentration in asthmatic and non-asthmatic patients was observed. However, higher concentrations of chemokines (MCP-1 and RANTES) in asthmatic patients infected by viruses, bacteria or bacteria and viruses (mixed) than in non-asthmatic patients were observed. In general, viral and mixed infections were better cytokine/chemokine inducers than bacterial infection. Cytokine/chemokine expression was similarly increased in both asthmatic and non-asthmatic patients with pneumonia or bronchitis, except that RANTES remained at normal levels in bronchitis. Circulating cytokine profiles induced by acute viral, bacterial or mixed lung infection were not related to asthmatic background, except for chemokines that were increased in asthmatic status. © 2017 The Foundation for the Scandinavian Journal of Immunology.

Dietary phosphate restriction normalizes biochemical and skeletal abnormalities in a murine model of tumoral calcinosis.

PubMed

Ichikawa, Shoji; Austin, Anthony M; Gray, Amie K; Allen, Matthew R; Econs, Michael J

2011-12-01

Mutations in the GALNT3 gene cause tumoral calcinosis characterized by ectopic calcifications due to persistent hyperphosphatemia. We recently developed Galnt3 knockout mice in a mixed background, which had hyperphosphatemia with increased bone mineral density (BMD) and infertility in males. To test the effect of dietary phosphate intake on their phenotype, Galnt3 knockout mice were generated in the C57BL/6J strain and fed various phosphate diets: 0.1% (low), 0.3% (low normal), 0.6% (normal), and 1.65% (high). Sera were analyzed for calcium, phosphorus, alkaline phosphatase, creatinine, blood urine nitrogen, 1,25-dihydroxyvitamin D, osteocalcin, tartrate-resistant acid phosphatase 5b, and fibroblast growth factor 23 (Fgf23). Femurs were evaluated by dual-energy x-ray absorptiometry, dynamic histomorphometry, and/or microcomputed tomography. Galnt3 knockout mice in C57BL/6J had the same biochemical phenotype observed in our previous study: hyperphosphatemia, inappropriately normal 1,25-dihydroxyvitamin D level, decreased alkaline phosphatase activity, and low intact Fgf23 concentration but high Fgf23 fragments. Skeletal analyses of their femurs revealed significantly high BMD with increased cortical bone area and trabecular bone volume. On all four phosphate diets, Galnt3 knockout mice had consistently higher phosphorus levels and lower alkaline phosphatase and intact Fgf23 concentrations than littermate controls. The low-phosphate diet normalized serum phosphorus, alkaline phosphatase, and areal BMD but failed to correct male infertility in Galnt3 knockout mice. The high-phosphate diet did not increase serum phosphorus concentration in either mutant or control mice due to a compensatory increase in circulating intact Fgf23 levels. In conclusion, dietary phosphate restriction normalizes biochemical and skeletal phenotypes of Galnt3 knockout mice and, thus, can be an effective therapy for tumoral calcinosis.

Dietary Phosphate Restriction Normalizes Biochemical and Skeletal Abnormalities in a Murine Model of Tumoral Calcinosis

PubMed Central

Austin, Anthony M.; Gray, Amie K.; Allen, Matthew R.; Econs, Michael J.

2011-01-01

Mutations in the GALNT3 gene cause tumoral calcinosis characterized by ectopic calcifications due to persistent hyperphosphatemia. We recently developed Galnt3 knockout mice in a mixed background, which had hyperphosphatemia with increased bone mineral density (BMD) and infertility in males. To test the effect of dietary phosphate intake on their phenotype, Galnt3 knockout mice were generated in the C57BL/6J strain and fed various phosphate diets: 0.1% (low), 0.3% (low normal), 0.6% (normal), and 1.65% (high). Sera were analyzed for calcium, phosphorus, alkaline phosphatase, creatinine, blood urine nitrogen, 1,25-dihydroxyvitamin D, osteocalcin, tartrate-resistant acid phosphatase 5b, and fibroblast growth factor 23 (Fgf23). Femurs were evaluated by dual-energy x-ray absorptiometry, dynamic histomorphometry, and/or microcomputed tomography. Galnt3 knockout mice in C57BL/6J had the same biochemical phenotype observed in our previous study: hyperphosphatemia, inappropriately normal 1,25-dihydroxyvitamin D level, decreased alkaline phosphatase activity, and low intact Fgf23 concentration but high Fgf23 fragments. Skeletal analyses of their femurs revealed significantly high BMD with increased cortical bone area and trabecular bone volume. On all four phosphate diets, Galnt3 knockout mice had consistently higher phosphorus levels and lower alkaline phosphatase and intact Fgf23 concentrations than littermate controls. The low-phosphate diet normalized serum phosphorus, alkaline phosphatase, and areal BMD but failed to correct male infertility in Galnt3 knockout mice. The high-phosphate diet did not increase serum phosphorus concentration in either mutant or control mice due to a compensatory increase in circulating intact Fgf23 levels. In conclusion, dietary phosphate restriction normalizes biochemical and skeletal phenotypes of Galnt3 knockout mice and, thus, can be an effective therapy for tumoral calcinosis. PMID:22009723

Diabetes Impairs the Vascular Recruitment of Normal Stem Cells by Oxidant Damage, Reversed by Increases in pAMPK, Heme Oxygenase-1, and Adiponectin

PubMed Central

Sambuceti, Gianmario; Morbelli, Silvia; Vanella, Luca; Kusmic, Claudia; Marini, Cecilia; Massollo, Michela; Augeri, Carla; Corselli, Mirko; Ghersi, Chiara; Chiavarina, Barbara; Rodella, Luigi F; L'Abbate, Antonio; Drummond, George; Abraham, Nader G; Frassoni, Francesco

2009-01-01

Background Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phosphorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. Conclusion Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponectin, and pAMPK levels. PMID:19038792

Pharmacokinetics of a combined oral contraceptive in obese and normal weight women

PubMed Central

Westhoff, Carolyn L.; Torgal, Anupama H.; Mayeda, Elizabeth R.; Pike, Malcolm C.; Stanczyk, Frank Z.

2010-01-01

Background This study was conducted to compare oral contraceptive (OC) pharmacokinetics (PK) in normal weight (BMI 19.0-24.9) and obese (BMI 30.0-39.9) women. Study Design During the third week of the third cycle of OC use, we admitted 15 normal weight and 15 obese women for collection of 12 venous specimens over 24 h. Using RIA techniques, we measured levels of ethinyl estradiol (EE) and levonorgestrel (LNG). During the same cycle, women underwent twice-weekly sonography to assess ovarian follicular development and blood draws to measure endogenous estradiol (E2) and progesterone levels. Results Obese women had a lower area under the curve (AUC; 1077.2 pg*h/mL vs 1413.7 pg*h/mL) and lower maximum values (85.7 pg/mL vs 129.5 pg/mL) for EE than normal weight women (p = 0.04 and 0.01, respectively); EE trough levels were similar between BMI groups. The similar, but smaller, differences in their LNG levels for AUC and maximum values (Cmax) were not statistically significant. While peak values differed somewhat, the LNG trough levels were similar for obese and normal weight women (2.6 ng/mL and 2.5 ng/mL, respectively). Women with greater EE AUC had smaller follicular diameters (p = 0.05) and lower E2 levels (p = 0.04). While follicular diameters tended to be larger among obese women, these differences were not statistically significant. Conclusion OC hormone peak levels are lower among obese women compared to normal weight women, but their trough levels are similar. In this small study, the observed PK differences did not translate into more ovarian follicular activity among obese OC users. PMID:20472113

One-Shot Learning of Human Activity With an MAP Adapted GMM and Simplex-HMM.

PubMed

Rodriguez, Mario; Orrite, Carlos; Medrano, Carlos; Makris, Dimitrios

2016-05-10

This paper presents a novel activity class representation using a single sequence for training. The contribution of this representation lays on the ability to train an one-shot learning recognition system, useful in new scenarios where capturing and labeling sequences is expensive or impractical. The method uses a universal background model of local descriptors obtained from source databases available on-line and adapts it to a new sequence in the target scenario through a maximum a posteriori adaptation. Each activity sample is encoded in a sequence of normalized bag of features and modeled by a new hidden Markov model formulation, where the expectation-maximization algorithm for training is modified to deal with observations consisting in vectors in a unit simplex. Extensive experiments in recognition have been performed using one-shot learning over the public datasets Weizmann, KTH, and IXMAS. These experiments demonstrate the discriminative properties of the representation and the validity of application in recognition systems, achieving state-of-the-art results.

High folic acid diet enhances tumour growth in PyMT-induced breast cancer

PubMed Central

Hansen, Mariann Fagernæs; Jensen, Sarah Østrup; Füchtbauer, Ernst-Martin; Martensen, Pia M

2017-01-01

Background: The B-vitamin folate is among the most studied bioactive food compound, and a dietary intake meeting the daily requirements has been found to reduce the risk of cancer and cardiovascular diseases as well as preventing neural tube defects during fetal development. Several countries have therefore introduced dietary fortification with folic acid. However, clinical and animal studies suggest that folic acid has a dual role in cancer development. Methods: During the period of initial tumour progression, MMTV-PyMT (MMTV-polyoma virus middle T) transgenic mice were fed with normal diet and high folic acid diet. Results: We found that PyMT-induced breast tumours highly express the cancer-specific folate receptor (FR), a feature they share with several human epithelial cancers in which expression of FRα correlates with tumour grade. Mice receiving a high folic acid diet displayed a significantly increased tumour volume compared with mice receiving normal diet. In the largest tumours, only found in mice on high folic acid diet, STAT3 was activated. In primary cells from PyMT tumours, STAT3 was activated upon treatment with folic acid in culture. Conclusions: Our results offer a novel molecular explanation for folic acid-induced growth of existing tumours. PMID:28152548

Development of hepatocellular carcinoma in Iqgap2-deficient mice is IQGAP1 dependent.

PubMed

Schmidt, Valentina A; Chiariello, Carmine S; Capilla, Encarnación; Miller, Frederick; Bahou, Wadie F

2008-03-01

IQGAPs are multidomain scaffolding proteins that integrate Rho GTPase and Ca2+/calmodulin signals with cell adhesive and cytoskeletal reorganizational events. Targeted disruption of the murine Iqgap2 gene resulted in the age-dependent development of apoptosis and hepatocellular carcinoma (HCC), characterized by the overexpression of IQGAP1, the loss of membrane E-cadherin expression, the cytoplasmic translocation (and activation) of beta-catenin, and the overexpression of a nuclear target of beta-catenin, cyclin D1. In normal hepatocytes, IQGAP2 was found to exist as one component of a multifunctional scaffolding complex comprising IQGAP1, beta-catenin, and E-cadherin, with no evidence for direct IQGAP1-IQGAP2 interactions. Interbreeding of Iqgap2(-/-) mice into the Iqgap1(-/-) background resulted in the phenotypic correction of the preexisting hepatopathy, decreases in the incidence and sizes of HCC tumors, and the normalization of overall survival rates compared to those of Iqgap2(-/-) mice, suggesting that maximal penetrance of the Iqgap2(-/-) HCC phenotype requires the coordinate expression of IQGAP1. These results identify Iqgap2 as a novel tumor suppressor gene specifically linked to the development of HCC and the activation of the Wnt/beta-catenin signaling pathway, while also suggesting that IQGAP1 and IQGAP2 retain functionally divergent roles in hepatocellular carcinogenesis.

Dynamics of testosterone concentration in male steppe lemmings (Lagurus lagurus) in the reproductive cycle reflects the species-specific mating system.

PubMed

Potapova, O F; Potapov, M A; Kondratyuk, E Yu; Evsikov, V I

2016-05-01

In the blood of male steppe lemmings, relatively low background levels of testosterone were detected, this is characteristic of a monogamous species. A significant increase in testosterone level, more expressed in sexually active males, was observed at the initial stage of formation of reproductive couples. Apparently, in the future, the couple will exist in a stable relationship, and, hence, the maintenance of a high testosterone level becomes excessive. The decrease in, and the relative "normalization" of, the hormone level during the existence of the pair, including raising of the young, promotes higher expression of the male paternal care of the offspring at the species level.

Design and implementation of an air monitoring program in support of a brownfields redevelopment program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maisel, B.E.; Hunt, G.T.; Devaney, R.J. Jr.

EPA`s Brownfields Economic Redevelopment Initiative has sparked renewal of industrial and commercial parcels otherwise idled or under-utilized because of real or perceived environmental contamination. In certain cases, restoring such parcels to productive economic use requires a redevelopment effort protective of human health and welfare through minimizing offsite migration of environmental contaminants during cleanup, demolition and remediation activities. To support these objectives, an air monitoring program is often required as an integral element of a comprehensive brownfields redevelopment effort. This paper presents a strategic framework for design and execution of an ambient air monitoring program in support of a brownfields remediationmore » effort ongoing in Lawrence, MA. Based on site characterization, the program included sample collection and laboratory analysis of ambient air samples for polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins and polychlorinated dibenzofurans (PCDDs/PCDFs), total suspended particulate (TSP), inhalable particulate (PM10), and lead. The program included four monitoring phases, identified as background, wintertime, demolition/remediation and post-demolition. Air sampling occurred over a 16 month period during 1996--97, during which time nine sampling locations were utilized to produce approximately 1,500 ambient air samples. Following strict data review and validation procedures, ambient air data interpretation focused on the following: evaluation of upwind/downwind sample pairs, comparison of ambient levels to existing regulatory standards, relation of ambient levels to data reported in the open literature, and, determination of normal seasonal variations in existing background burden, comparison of ambient levels measured during site activity to background levels.« less

Hong Kong Parents' Perceptions of Benefits of Music to Their Children

ERIC Educational Resources Information Center

Choi, Angel Lai Yan; Tse, Jennie Chen Yee; So, Cindy Sin Ni; Yeung, Alexander Seeshing

2005-01-01

Background: In Hong Kong, many parents encourage their children to take extra music lessons beyond normal school hours. This study investigates parents' perceptions of the benefits of music to children. Aims: To investigate why many parents in Hong Kong encourage their children to take extra music lessons beyond normal school hours, and to examine…

Speech Perception with Music Maskers by Cochlear Implant Users and Normal-Hearing Listeners

ERIC Educational Resources Information Center

Eskridge, Elizabeth N.; Galvin, John J., III; Aronoff, Justin M.; Li, Tianhao; Fu, Qian-Jie

2012-01-01

Purpose: The goal of this study was to investigate how the spectral and temporal properties in background music may interfere with cochlear implant (CI) and normal-hearing listeners' (NH) speech understanding. Method: Speech-recognition thresholds (SRTs) were adaptively measured in 11 CI and 9 NH subjects. CI subjects were tested while using their…

Long-term variations in the gamma-ray background on SMM

NASA Technical Reports Server (NTRS)

Kurfess, J. D.; Share, G. H.; Kinzer, R. L.; Johnson, W. N.; Adams, J. H., Jr.

1989-01-01

Long-term temporal variations in the various components of the background radiation detected by the gamma-ray spectrometer on the Solar Maximum Mission are presented. The SMM gamma-ray spectrometer was launched in February, 1980 and continues to operate normally. The extended period of mission operations has provided a large data base in which it is possible to investigate a variety of environmental and instrumental background effects. In particular, several effects associated with orbital precession are introduced and discussed.

Evidence for linkages between ecoenzyme activity and soil organic matter chemistry following encroachment of leguminous woody plant into grasslands.

NASA Astrophysics Data System (ADS)

Filley, Timothy; Stott, Diane; Boutton, Thomas; Creamer, Courtney; Olk, Dan

2010-05-01

The encroachment of woody plants into grasslands is a worldwide phenomenon. In the Rio Grande Plains of southern Texas, subtropical thorn woodlands dominated by the N-fixing tree Prosopis glandulosa have largely replaced native grasslands as a result of fire suppression and extensive cattle grazing. This land cover change has resulted in the increase of belowground stocks of C, N, and P, changes to the amount and chemical nature of soil-stabilized plant biopolymers, and the composition and activity of soil microbes. Given that extracellular enzymes produced by plants and microbes are the principal means by which complex compounds are degraded and that the production of such enzymes is triggered or suppressed by changes in substrate and nutrient availability we sought to relate how these fundamental changes in this ecosystem are reflected in the activity of soil stabilized ecoenzymes and soil organic matter (SOM) chemistry in this system. We investigated a chronosequence of woody encroachment (14-86 yrs) into a C4-dominant grassland. We related the potential activities of five extracellular enzymes (arylamidase, acid phosphatase, β-glucosidase, β-glucosaminidase (NAGase, polyphenoloxidase (PPO)) and a general marker for hydrolytic activity, fluorescein diacetate (FDA) to the molecular composition and concentration of total hydrolysable amino acids and amino sugars, sugars, as well as CuO extractable lignin and substituted fatty acid to. When normalized to dry weight soil all chemical components increase in concentration with cluster age and all clusters have greater concentrations than background grasslands. All enzymes activities exhibit higher potential activity in woody clusters than grasslands but only NAGase and FDA increase with cluster age when normalized to dry weight of soil. Conversely, when normalized to SOC only lignin phenols, hydroxyl proline, and glucose from cellulose are positively correlated with cluster age indicating a selective accrual with respect to bulk Corg accrual. The opposite relationship between PPO and lignin indicates a suppression of PPO activity possibly by N-accrual in this leguminous system. Other relationships are evident among enzymes and land cover/age profiles and will be discussed. These results have important implications for the modeling of woodland-grassland conversion and the dynamics of biogeochemical cycles in this globally significant land cover change.

Discriminating colors through a red filter by protanopes and colour normals.

PubMed

Diaconu, Vasile; Sullivan, David; Bouchard, Jean F; Vucea, Valentina

2010-01-01

Individuals with color vision deficiency have difficulties in differentiating colour in their daily activities. Through certain coloured filters, dichromats may report an improvement of their capacity to differentiate colors, but it is not known if this is achieved by means of a chromatic mechanism. The present study attempts to explain the mechanism by which a coloured filter can produce a beneficial effect in dichromatic visual perception and what is the nature of this improvement. Four male protanopes and four normal trichromats (two males and two females) participated in the present study. We evaluated the effect of the red filter (with a spectral transmittance similar to that of the X-Chrom filter) on the detection thresholds for monochromatic light stimuli from 420 to 660 nm in 20 nm steps. The increment spectral sensitivity functions were measured for 1.2 degrees diameter test flashes presented for 300 ms on a 60-cd m(-2) illuminant C background using an optical bench with a monochromator, for both filter and no filter conditions. The capacity to correctly name green, yellow and red for the monochromatic lights of 550, 575 and 625 nm presented for 300 ms on a 60 cd m(-2) illuminant C background screen was also evaluated with and without the red filter. The spectral sensitivity data suggest that, the use of a red filter improves the protanope's capacity to detect long wavelength light stimuli. The results on the colors naming procedure demonstrate that the red filter modifies colour perception in normal and protanope subjects. In normals, only the red color perception is preserved, and typical colour perception for the green and the yellow is lost. Without the filter, all the protanopes demonstrated a residual colour perception for red and green colours. Through the red filter only red colour perception remains. A red filter does not improve the protanopic red-green perception, but it does improve the ability of the protanope to detect long-wavelength light. This improvement seems to arise by means of the luminance mechanism.

Cadmium partition in river sediments from an area affected by mining activities.

PubMed

Vasile, Georgiana D; Vlădescu, Luminiţa

2010-08-01

In this paper, the cadmium distribution in Certej River sediments in an area seriously affected by intense mining activities has been studied. The main objective of this study was the evaluation of partition of this metal into different operational defined fractions by sequential extractions. Community Bureau of Reference (BCR) sequential extraction was used to isolate different fractions. The sediment quality was assessed both upstream and downstream the pollution input points, along the Certej River, in order to reveal a possible accumulation of cadmium in sediments and the seasonal changes in cadmium concentrations in BCR sediment phases. Our results reveal that most of the cadmium content is divided between both the soluble and iron and manganese hydrated oxide fractions. Based on total cadmium concentrations in sediments, the enrichment factors were estimated using aluminum as normalizing element and the regression curve Cd/Al corresponding to the geochemical background of the studied area.

Sexual function and practice in elderly men of lower socioeconomic status.

PubMed

Cogen, R; Steinman, W

1990-08-01

Normal aging plus certain prevalent diseases are believed to render many elderly men impotent. Recent studies have suggested that educated middle-class and upper-class elderly men continue sexual activity, despite erectile dysfunction, by employing alternative practices such as mutual masturbation and oral sex. Few elderly men of lower socioeconomic background have been included in these studies, however. Using physician-administered interviews, 87 men attending an urban Veterans Administration geriatric clinic were studied to determine (1) the prevalence of erectile dysfunction, and (2) the sexual practices and attitudes of this group. Of the 87 men, 28% reported complete loss of erectile function, while 31% had frequent difficulties achieving vaginal intromission. Unlike economically advantaged groups, only 29% used mutual masturbation and 16% used oral sex. Attitudes toward these practices were negative. With one exception, men unable to perform coitus ceased all heterosexual activities.

A gamma-gamma coincidence/anticoincidence spectrometer for low-level cosmogenic (22)Na/(7)Be activity ratio measurement.

PubMed

Zhang, Weihua; Ungar, Kurt; Stukel, Matthew; Mekarski, Pawel

2014-04-01

In this study, a digital gamma-gamma coincidence/anticoincidence spectrometer was developed and examined for low-level cosmogenic (22)Na and (7)Be in air-filter sample monitoring. The spectrometer consists of two bismuth germanate scintillators (BGO) and an XIA LLC Digital Gamma Finder (DGF)/Pixie-4 software and card package. The spectrometer design allows a more selective measurement of (22)Na with a significant background reduction by gamma-gamma coincidence events processing. Hence, the system provides a more sensitive way to quantify trace amounts of (22)Na than normal high resolution gamma spectrometry providing a critical limit of 3 mBq within a 20 h count. The use of a list-mode data acquisition technique enabled simultaneous determination of (22)Na and (7)Be activity concentrations using a single measurement by coincidence and anticoincidence mode respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes

PubMed Central

Santhosh, KT; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, AJ; Dakshinamurti, S

2011-01-01

BACKGROUND AND PURPOSE Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor–mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. EXPERIMENTAL APPROACH We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca2+ response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. KEY RESULTS Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. CONCLUSIONS AND IMPLICATIONS TP receptor sensitivity and EC50 for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca2+ mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. PMID:21385177

Tinnitus Intensity Dependent Gamma Oscillations of the Contralateral Auditory Cortex

PubMed Central

van der Loo, Elsa; Gais, Steffen; Congedo, Marco; Vanneste, Sven; Plazier, Mark; Menovsky, Tomas; Van de Heyning, Paul; De Ridder, Dirk

2009-01-01

Background Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores. Methods and Findings In unilateral tinnitus patients (N = 15; 10 right, 5 left) source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05). Conclusion Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception. PMID:19816597

Influence of Marriage and Parenthood on Physical Activity: A 2-Year Prospective Analysis

PubMed Central

Hull, Ethan Edward; Rofey, Dana L.; Robertson, Robert J.; Nagle, Elizabeth F.; Otto, Amy D.; Aaron, Deborah J.

2011-01-01

Background Physical activity (PA) tends to decrease from adolescence to young adulthood, and factors that have been proposed to contribute to this decrease are life transitions. The focus of this study is to examine life transitions, such as marriage and parenthood, and the impact they may have on the physical activity levels of young adults. Methods This 2-year prospective analysis assessed physical activity (hrs/wk) and sociodemographics in young adults (n = 638, 48% male, 15% nonwhite, 24 ± 1.1 years old) via questionnaire. PA data were normalized through log transformations and examined using ANCOVAs, controlling for appropriate covariates. Results ANCOVA results showed that becoming married did not significantly change PA compared with individuals who stayed single [F(1,338) = 0.38, P = .54, d = 0.06]. Conversely, PA was significantly lower [F(1,517) = 6.7, P = .01, d = 0.41] after having a child, compared with individuals who stayed childless. Conclusions These results suggest that marriage does not impact PA in young adults, but having a child significantly decreases PA in parents, and may offer an optimal period of intervention. PMID:20864752

Analysis of the mechanism of activation of cAMP-dependent protein kinase through the study of mutants of the yeast regulatory subunit.

PubMed

Zaremberg, V; Moreno, S

1996-04-01

Spontaneous mutations in the gene which encodes the regulatory subunit of cAMP-dependent protein kinase (PKA) of Saccharomyces cerevisiae (BCY1) have been isolated previously [Cannon, J. F., Gibbs, J. B. & Tatchell, K. (1986) Genetics 113, 247-264] by selection of ras2::LEU2 revertants that grew on non-fermentable carbon sources. The revertants were placed into groups of increasing severity based on the number of PKA-dependent traits affected [Cannon, J. F., Gitan, R. & Tatchell, K. (1990) J. Biol. Chem. 265, 11897-11904]. In this work the ras2 mutation has been crossed out in each bcy1 allele and the phenotypes of these mutants have been assessed. The order of severity of the mutants in both genetic backgrounds is maintained but the severity of each mutant in the normal background is higher than in the ras2::LEU2 background. Total catalytic-subunit and regulatory-subunit activities were measured in crude extracts of the bcy1 ras2::LEU2 mutants. With one exception (bcy1-6) the calculated regulatory subunit/catalytic subunit ratios of the bcy1 mutants relative to that of wild-type cells were greater than one. The dependence of PKA activity on cAMP was measured in permeabilized cells. The strains show an activity ratio in the absence and presence of cAMP in the range 0.5-1 for Kemptide phosphorylation. Overexpression of the high-affinity cAMP phosphodiesterase gene (PDE2) in the bcy1 ras2::LEU2 strains did not alter their PKA-dependent phenotypes. However, transformants were not observed from the parental ras2::LEU2 strain and the bcy1-6 ras2::LEU2 strain. The results are discussed with respect to a hypothesis for the molecular mechanism of the differential reversal of ras2 phenotypes by the bcy1 alleles. Mutations in the regulatory subunit are predicted to affect the structure of the holoenzyme such that the catalytic subunit is capable of maintaining an active catalytic state, without the need to dissociate from the regulatory subunit.

A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and intestinal function in pediatric patients

PubMed Central

Sigalet, David L; Kravarusic, Dragan; Butzner, Decker; Hartmann, Bolette; Holst, Jens J; Meddings, Jon

2013-01-01

BACKGROUND/OBJECTIVES: The relationship between the enteroendocrine hormone glucagon-like peptide 2 (GLP-2) and intestinal inflammation is unclear. GLP-2 promotes mucosal growth, decreases permeability and reduces inflammation in the intestine; physiological stimulation of GLP-2 release is triggered by nutrient contact. The authors hypothesized that ileal Crohn disease (CD) affects GLP-2 release. METHODS: With ethics board approval, pediatric patients hospitalized with CD were studied; controls were recruited from local schools. Inclusion criteria were endoscopy-confirmed CD (primarily of the small intestine) with a disease activity index >150. Fasting and post-prandial GLP-2 levels and quantitative urinary recovery of orally administered 3-O-methyl-glucose (active transport) and lactulose/mannitol (passive) were quantified during the acute and remission phases. RESULTS: Seven patients (mean [± SD] age 15.3±1.3 years) and 10 controls (10.3±1.6 years) were studied. In patients with active disease, fasting levels of GLP-2 remained stable but postprandial levels were reduced. Patients with active disease exhibited reduced glucose absorption and increased lactulose/mannitol recovery; all normalized with disease remission. The change in the lactulose/mannitol ratio was due to both reduced lactulose and increased mannitol absorption. CONCLUSIONS: These findings suggest that pediatric patients with acute ileal CD have decreased postprandial GLP-2 release, reduced glucose absorption and increased intestinal permeability. Healing of CD resulted in normalization of postprandial GLP-2 release and mucosal functioning (nutrient absorption and permeability), the latter due to an increase in mucosal surface area. These findings have implications for the use of GLP-2 and feeding strategies as a therapy in CD patients; further studies of the effects of inflammation and the GLP-2 axis are recommended. PMID:24106731

Examining Coherency Scales, Substructure, and Propagation of Whistler Mode Chorus Elements With Magnetospheric Multiscale (MMS)

NASA Astrophysics Data System (ADS)

Turner, D. L.; Lee, J. H.; Claudepierre, S. G.; Fennell, J. F.; Blake, J. B.; Jaynes, A. N.; Leonard, T.; Wilder, F. D.; Ergun, R. E.; Baker, D. N.; Cohen, I. J.; Mauk, B. H.; Strangeway, R. J.; Hartley, D. P.; Kletzing, C. A.; Breuillard, H.; Le Contel, O.; Khotyaintsev, Yu. V.; Torbert, R. B.; Allen, R. C.; Burch, J. L.; Santolik, O.

2017-11-01

Whistler mode chorus waves are a naturally occurring electromagnetic emission observed in Earth's magnetosphere. Here, for the first time, data from NASA's Magnetospheric Multiscale (MMS) mission were used to analyze chorus waves in detail, including the calculation of chorus wave normal vectors, fi>k. A case study was examined from a period of substorm activity around the time of a conjunction between the MMS constellation and NASA's Van Allen Probes mission on 07 April 2016. Chorus wave activity was simultaneously observed by all six spacecraft over a broad range of L shells (5.5 < L < 8.5), magnetic local time (06:00 < MLT < 09:00), and magnetic latitude (-32° < MLAT < -15°), implying a large chorus active region. Eight chorus elements and their substructure were analyzed in detail with MMS. These chorus elements were all lower band and rising tone emissions, right-handed and nearly circularly polarized, and propagating away from the magnetic equator when they were observed at MMS (MLAT -31°). Most of the elements had "hook"-like signatures on their wave power spectra, characterized by enhanced wave power at flat or falling frequency following the peak, and all the elements exhibited complex and well-organized substructure observed consistently at all four MMS spacecraft at separations up to 70 km (60 km perpendicular and 38 km parallel to the background magnetic field). The waveforms in field-aligned coordinates also demonstrated that these waves were all phase coherent, allowing for the direct calculation of fi>k. Error estimates on calculated fi>k revealed that the plane wave approximation was valid for six of the eight elements and most of the subelements. The wave normal vectors were within 20-30° from the direction antiparallel to the background field for all elements and changed from subelement to subelement through at least two of the eight elements. The azimuthal angle of fi>k in the perpendicular plane was oriented earthward and was oblique to that of the Poynting vector, which has implications for the validity of cold plasma theory.

Active Galactic Nuclei, Host Star Formation, and the Far Infrared

NASA Astrophysics Data System (ADS)

Draper, Aden R.; Ballantyne, D. R.

2011-05-01

Telescopes like Herschel and the Atacama Large Millimeter/submillimeter Array (ALMA) are creating new opportunities to study sources in the far infrared (FIR), a wavelength region dominated by cold dust emission. Probing cold dust in active galaxies allows for study of the star formation history of active galactic nuclei (AGN) hosts. The FIR is also an important spectral region for observing AGN which are heavily enshrouded by dust, such as Compton thick (CT) AGN. By using information from deep X-ray surveys and cosmic X-ray background synthesis models, we compute Cloudy photoionization simulations which are used to predict the spectral energy distribution (SED) of AGN in the FIR. Expected differential number counts of AGN and their host galaxies are calculated in the Herschel bands. The expected contribution of AGN and their hosts to the cosmic infrared background (CIRB) is also computed. Multiple star formation scenarios are investigated using a modified blackbody star formation SED. It is found that FIR observations at 350 and 500 um are an excellent tool in determining the star formation history of AGN hosts. Additionally, the AGN contribution to the CIRB can be used to determine whether star formation in AGN hosts evolves differently than in normal galaxies. AGN and host differential number counts are dominated by CT AGN in the Herschel-SPIRE bands. Therefore, X-ray stacking of bright SPIRE sources is likely to disclose a large fraction of the CT AGN population.

Properties and Expected Number Counts of Active Galactic Nuclei and Their Hosts in the Far-infrared

NASA Astrophysics Data System (ADS)

Draper, A. R.; Ballantyne, D. R.

2011-03-01

Telescopes like Herschel and the Atacama Large Millimeter/submillimeter Array (ALMA) are creating new opportunities to study sources in the far-infrared (FIR), a wavelength region dominated by cold dust emission. Probing cold dust in active galaxies allows for study of the star formation history of active galactic nucleus (AGN) hosts. The FIR is also an important spectral region for observing AGNs which are heavily enshrouded by dust, such as Compton thick (CT) AGNs. By using information from deep X-ray surveys and cosmic X-ray background synthesis models, we compute Cloudy photoionization simulations which are used to predict the spectral energy distribution (SED) of AGNs in the FIR. Expected differential number counts of AGNs and their host galaxies are calculated in the Herschel bands. The expected contribution of AGNs and their hosts to the cosmic infrared background (CIRB) and the infrared luminosity density are also computed. Multiple star formation scenarios are investigated using a modified blackbody star formation SED. It is found that FIR observations at ~500 μm are an excellent tool in determining the star formation history of AGN hosts. Additionally, the AGN contribution to the CIRB can be used to determine whether star formation in AGN hosts evolves differently than in normal galaxies. The contribution of CT AGNs to the bright end differential number counts and to the bright source infrared luminosity density is a good test of AGN evolution models where quasars are triggered by major mergers.

Wound healing properties of ethyl acetate fraction of Moringa oleifera in normal human dermal fibroblasts

PubMed Central

Gothai, Sivapragasam; Arulselvan, Palanisamy; Tan, Woan Sean; Fakurazi, Sharida

2016-01-01

Background/Aim: Wounds are the outcome of injuries to the skin that interrupt the soft tissue. Healing of a wound is a complex and long-drawn-out process of tissue repair and remodeling in response to injury. A large number of plants are used by folklore traditions for the treatment of cuts, wounds and burns. Moringa oleifera (MO) is an herb used as a traditional folk medicine for the treatment of various skin wounds and associated diseases. The underlying mechanisms of wound healing activity of ethyl acetate fraction of MO leaves extract are completely unknown. Materials and Methods: In the current study, ethyl acetate fraction of MO leaves was investigated for its efficacy on cell viability, proliferation and migration (wound closure rate) in human normal dermal fibroblast cells. Results: Results revealed that lower concentration (12.5 µg/ml, 25 µg/ml, and 50 µg/ml) of ethyl acetate fraction of MO leaves showed remarkable proliferative and migratory effect on normal human dermal fibroblasts. Conclusion: This study suggested that ethyl acetate fraction of MO leaves might be a potential therapeutic agent for skin wound healing by promoting fibroblast proliferation and migration through increasing the wound closure rate corroborating its traditional use. PMID:27069722

Speech intelligibility with helicopter noise: tests of three helmet-mounted communication systems.

PubMed

Ribera, John E; Mozo, Ben T; Murphy, Barbara A

2004-02-01

Military aviator helmet communications systems are designed to enhance speech intelligibility (SI) in background noise and reduce exposure to harmful levels of noise. Some aviators, over the course of their aviation career, develop noise-induced hearing loss that may affect their ability to perform required tasks. New technology can improve SI in noise for aviators with normal hearing as well as those with hearing loss. SI in noise scores were obtained from 40 rotary-wing aviators (20 with normal hearing and 20 with hearing-loss waivers). There were three communications systems evaluated: a standard SPH-4B, an SPH-4B aviator helmet modified with communications earplug (CEP), and an SPH-4B modified with active noise reduction (ANR). Subjects' SI was better in noise with newer technologies than with the standard issue aviator helmet. A significant number of aviators on waivers for hearing loss performed within the range of their normal hearing counterparts when wearing the newer technology. The rank order of perceived speech clarity was 1) CEP, 2) ANR, and 3) unmodified SPH-4B. To insure optimum SI in noise for rotary-wing aviators, consideration should be given to retrofitting existing aviator helmets with new technology, and incorporating such advances in communication systems of the future. Review of standards for determining fitness to fly is needed.

Improved Discovery of Molecular Interactions in Genome-Scale Data with Adaptive Model-Based Normalization

PubMed Central

Brown, Patrick O.

2013-01-01

Background High throughput molecular-interaction studies using immunoprecipitations (IP) or affinity purifications are powerful and widely used in biology research. One of many important applications of this method is to identify the set of RNAs that interact with a particular RNA-binding protein (RBP). Here, the unique statistical challenge presented is to delineate a specific set of RNAs that are enriched in one sample relative to another, typically a specific IP compared to a non-specific control to model background. The choice of normalization procedure critically impacts the number of RNAs that will be identified as interacting with an RBP at a given significance threshold – yet existing normalization methods make assumptions that are often fundamentally inaccurate when applied to IP enrichment data. Methods In this paper, we present a new normalization methodology that is specifically designed for identifying enriched RNA or DNA sequences in an IP. The normalization (called adaptive or AD normalization) uses a basic model of the IP experiment and is not a variant of mean, quantile, or other methodology previously proposed. The approach is evaluated statistically and tested with simulated and empirical data. Results and Conclusions The adaptive (AD) normalization method results in a greatly increased range in the number of enriched RNAs identified, fewer false positives, and overall better concordance with independent biological evidence, for the RBPs we analyzed, compared to median normalization. The approach is also applicable to the study of pairwise RNA, DNA and protein interactions such as the analysis of transcription factors via chromatin immunoprecipitation (ChIP) or any other experiments where samples from two conditions, one of which contains an enriched subset of the other, are studied. PMID:23349766

Effects of combined physical education and nutritional programs on schoolchildren’s healthy habits

PubMed Central

Gallotta, Maria Chiara; Iazzoni, Sara; Emerenziani, Gian Pietro; Meucci, Marco; Migliaccio, Silvia; Guidetti, Laura

2016-01-01

Background. A multidisciplinary approach seems to be effective in creating healthy habits in children. The aim of this study was to evaluate the efficacy of three 5-month combined physical education (PE) and nutritional interventions on body composition, physical activity (PA) level, sedentary time and eating habits of schoolchildren. Methods. Anthropometric data, weekly PA level, sedentary time and eating habits of 230 healthy students were analysed using a repeated-measures ANOVA with Group (experimental group 1 vs experimental group 2 vs control group), Adiposity Status (under fat vs normal fat vs obese), and Time (pre vs post) as factors. Results. Body fat mass percentage increased after intervention (18.92 ± 8.61% vs 19.40 ± 8.51%) in all groups. The weekly PA level significantly increased after intervention in both experimental groups. Sedentary time significantly decreased after the intervention period (565.70 ± 252.93 vs 492.10 ± 230.97 min/week, p < 0.0001). Moreover, obese children were more sedentary than under fat and normal fat children. Children significantly changed the consumption of some specific foods after intervention. Discussion. This study revealed the effectiveness of a combined PE and nutritional intervention to improve children’s healthful dietary practices and to encourage an active lifestyle. However, it needs a further appropriate development to establish patterns of healthful dietary practices that encourage an active lifestyle with which to maintain healthy habits through life. PMID:27077004

Peripheral Prism Glasses: Effects of Dominance, Suppression and Background

PubMed Central

Ross, Nicole C.; Bowers, Alex R.; Optom, M.C.; Peli, Eli

2012-01-01

Purpose Unilateral peripheral prisms for homonymous hemianopia (HH) place different images on corresponding peripheral retinal points, a rivalrous situation in which local suppression of the prism image could occur and thus limit device functionality. Detection with peripheral prisms has primarily been evaluated using conventional perimetry where binocular rivalry is unlikely to occur. We quantified detection over more visually complex backgrounds and examined the effects of ocular dominance. Methods Detection rates of 8 participants with HH or quadranopia and normal binocularity wearing unilateral peripheral prism glasses were determined for static perimetry targets briefly presented in the prism expansion area (in the blind hemifield) and the seeing hemifield, under monocular and binocular viewing, over uniform gray and more complex patterned backgrounds. Results Participants with normal binocularity had mixed sensory ocular dominance, demonstrated no difference in detection rates when prisms were fitted on the side of the HH or the opposite side (p>0.2), and had detection rates in the expansion area that were not different for monocular and binocular viewing over both backgrounds (p>0.4). However, two participants with abnormal binocularity and strong ocular dominance demonstrated reduced detection in the expansion area when prisms were fitted in front of the non-dominant eye. Conclusions We found little evidence of local suppression of the peripheral prism image for HH patients with normal binocularity. However, in cases of strong ocular dominance, consideration should be given to fitting prisms before the dominant eye. Although these results are promising, further testing in more realistic conditions including image motion is needed. PMID:22885783

Cognitive skills and academic achievement of deaf children with cochlear implants.

PubMed

Huber, Maria; Kipman, Ulrike

2012-10-01

To compare cognitive performance between children with cochlear implants (CI) and normal-hearing peers; provide information about correlations between cognitive performance, basic academic achievement, and medical/audiological and social background variables; and assess the predictor quality of these variables for cognition. Cross-sectional study with comparison group, diagnostic test assessment. Data were collected in the authors' clinic (children with CI) and in Austrian schools (normal-hearing children). Forty children with CI (of the initial 65 children eligible for this study), aged 7 to 11 years, and 40 normal-hearing children, matched by age and sex, were tested with (a) the Culture Fair Intelligence Test (CFIT); (b) the Number Sequences subtest of the Heidelberger Rechentest 1-4 (HRT); (c) Comprehension, (d) Coding, (e) Digit Span, and (f) Vocabulary subtests of HAWIK III (German WISC III); (g) the Corsi Block Tapping Test; (h) the Arithmetic Operations subtests of the HRT; and (i) Salzburger Lese-Screening (SLS, reading). In addition, medical, audiological, social, and educational data from children with CI were collected. The children with CI equaled normal-hearing children in (a), (d), (e), (g), (h), and (i) and performed significantly worse in (b), (c) and (f). Background variables correlate significantly with cognitive skills and academic achievement. Medical/audiological variables explain 44.3% of the variance in CFT1 (CFIT, younger children). Social variables explain 55% of CFT1 and 24.5% of the Corsi test. This study augments the knowledge about cognitive skills and academic skills of children with CI. Cognitive performance is dependent on the early feasibility to hear and the social/educational background of the family.

Joint Angular Velocity in Spastic Gait and the Influence of Muscle-Tendon Lengthening*

PubMed Central

GRANATA, KEVIN P.; ABEL, MARK F.; DAMIANO, DIANE L.

2006-01-01

Background Joint angular velocity (the rate of flexion and extension of a joint) is related to the dynamics of muscle activation and force generation during walking. Therefore, the goal of this research was to examine the joint angular velocity in normal and spastic gait and changes resulting from muscle-tendon lengthening (recession and tenotomy) in patients who have spastic cerebral palsy. Methods The gait patterns of forty patients who had been diagnosed with spastic cerebral palsy (mean age, 8.3 years; range, 3.7 to 14.8 years) and of seventy-three age-matched, normally developing subjects were evaluated with three-dimensional motion analysis and electromyography. The patients who had cerebral palsy were evaluated before muscle-tendon lengthening and nine months after treatment. Results The gait patterns of the patients who had cerebral palsy were characterized by increased flexion of the knee in the stance phase, premature plantar flexion of the ankle, and reduced joint angular velocities compared with the patterns of the normally developing subjects. Even though muscle-tendon lengthening altered sagittal joint angles in gait, the joint angular velocities were generally unchanged at the hip and knee. Only the ankle demonstrated modified angular velocities, including reduced dorsiflexion velocity at foot-strike and improved dorsiflexion velocity through midstance, after treatment. Electromyographic changes included reduced amplitude of the gastrocnemius-soleus during the loading phase and decreased knee coactivity (the ratio of quadriceps and hamstring activation) at toe-off. Principal component analyses showed that, compared with joint-angle data, joint angular velocity was better able to discriminate between the gait patterns of the normal and cerebral palsy groups. Conclusions This study showed that muscle-tendon lengthening corrects biomechanical alignment as reflected by changes in sagittal joint angles. However, joint angular velocity and electromyographic data suggest that the underlying neural input remains largely unchanged at the hip and knee. Conversely, electromyographic changes and changes in velocity in the ankle indicate that the activation pattern of the gastrocnemius-soleus complex in response to stretch was altered by recession of the complex. PMID:10682726

50 CFR 300.35 - Vessel and gear identification.

Code of Federal Regulations, 2014 CFR

2014-10-01

... being at least 1 m high and having a stroke width of 16.7 cm, with the background extending to provide a... stroke width of 5 cm with the background extending to provide a border around the mark of not less than 5... normal fishing operations, with each letter and number being at least 10 cm high and having a stroke...

50 CFR 300.35 - Vessel and gear identification.

Code of Federal Regulations, 2010 CFR

2010-10-01

... being at least 1 m high and having a stroke width of 16.7 cm, with the background extending to provide a... stroke width of 5 cm with the background extending to provide a border around the mark of not less than 5... normal fishing operations, with each letter and number being at least 10 cm high and having a stroke...

50 CFR 300.35 - Vessel and gear identification.

Code of Federal Regulations, 2013 CFR

2013-10-01

... being at least 1 m high and having a stroke width of 16.7 cm, with the background extending to provide a... stroke width of 5 cm with the background extending to provide a border around the mark of not less than 5... normal fishing operations, with each letter and number being at least 10 cm high and having a stroke...

50 CFR 300.35 - Vessel and gear identification.

Code of Federal Regulations, 2011 CFR

2011-10-01

... being at least 1 m high and having a stroke width of 16.7 cm, with the background extending to provide a... stroke width of 5 cm with the background extending to provide a border around the mark of not less than 5... normal fishing operations, with each letter and number being at least 10 cm high and having a stroke...

50 CFR 300.35 - Vessel and gear identification.

Code of Federal Regulations, 2012 CFR

2012-10-01

... being at least 1 m high and having a stroke width of 16.7 cm, with the background extending to provide a... stroke width of 5 cm with the background extending to provide a border around the mark of not less than 5... normal fishing operations, with each letter and number being at least 10 cm high and having a stroke...

The X-ray background contributed by QSOs ejected from galaxies

NASA Technical Reports Server (NTRS)

Burbidge, G.; Hoyle, F.

1996-01-01

The X-ray background can be explained as coming from the integrated effect of X-ray emitting quasi-stellar objects (QSOs) ejected from spiral galaxies. The model developed to interpret the observations is summarized. The redshift of the QSOs consisted of an intrinsic component and of a cosmological component. The QSOs have a spatial density proportional to that of normal galaxies.

--No Title--

Science.gov Websites

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Solar energetic particle events in different types of solar wind

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kahler, S. W.; Vourlidas, A., E-mail: stephen.kahler@kirtland.af.mil

2014-08-10

We examine statistically some properties of 96 20 MeV gradual solar energetic proton (SEP) events as a function of three different types of solar wind (SW) as classified by Richardson and Cane. Gradual SEP (E > 10 MeV) events are produced in shocks driven by fast (V ≳ 900 km s{sup –1}) and wide (W > 60°) coronal mass ejections (CMEs). We find no differences among the transient, fast, and slow SW streams for SEP 20 MeV proton event timescales. It has recently been found that the peak intensities Ip of these SEP events scale with the ∼2 MeV protonmore » background intensities, which may be a proxy for the near-Sun shock seed particles. Both the intensities Ip and their 2 MeV backgrounds are significantly enhanced in transient SW compared to those of fast and slow SW streams, and the values of Ip normalized to the 2 MeV backgrounds only weakly correlate with CME V for all SW types. This result implies that forecasts of SEP events could be improved by monitoring both the Sun and the local SW stream properties and that the well known power-law size distributions of Ip may differ between transient and long-lived SW streams. We interpret an observed correlation between CME V and the 2 MeV background for SEP events in transient SW as a manifestation of enhanced solar activity.« less

Effects of Background Lighting Color and Movement Distance on Reaching Times Among Participants With Low Vision, Myopia, and Normal Vision.

PubMed

Chen, Chun-Fu; Huang, Kuo-Chen

2016-04-01

This study investigated the effects of target distance (30, 35, and 40 cm) and the color of background lighting (red, green, blue, and yellow) on the duration of movements made by participants with low vision, myopia, and normal vision while performing a reaching task; 48 students (21 women, 27 men; M age = 21.8 year, SD = 2.4) participated in the study. Participants reached for a target (a white LED light) whose vertical position varied randomly across trials, ranging in distance from 30 to 40 cm. Movement time was analyzed using a 3 (participant group) × [4 (color of background lighting) × 3 (movement distance)] mixed-design ANOVA model. Results indicated longer times for completing a reaching movement when: participants belonged to the low vision group; the target distance between the starting position and the target position was longer (40 cm); and the reaching movement occurred in the red-background lighting condition. These results are particularly relevant for situations in which a user is required to respond to a signal by reaching toward a button or an icon. © The Author(s) 2016.

Optical Flow for Flight and Wind Tunnel Background Oriented Schlieren Imaging

NASA Technical Reports Server (NTRS)

Smith, Nathanial T.; Heineck, James T.; Schairer, Edward T.

2017-01-01

Background oriented Schlieren images have historically been generated by calculating the observed pixel displacement between a wind-on and wind-o image pair using normalized cross-correlation. This work uses optical flow to solve the displacement fields which generate the Schlieren images. A well established method used in the computer vision community, optical flow is the apparent motion in an image sequence due to brightness changes. The regularization method of Horn and Schunck is used to create Schlieren images using two data sets: a supersonic jet plume shock interaction from the NASA Ames Unitary Plan Wind Tunnel, and a transonic flight test of a T-38 aircraft using a naturally occurring background, performed in conjunction with NASA Ames and Armstrong Research Centers. Results are presented and contrasted with those using normalized cross-correlation. The optical flow Schlieren images are found to provided significantly more detail. We apply the method to historical data sets to demonstrate the broad applicability and limitations of the technique.

Activity of upper limb muscles during human walking.

PubMed

Kuhtz-Buschbeck, Johann P; Jing, Bo

2012-04-01

The EMG activity of upper limb muscles during human gait has rarely been studied previously. It was examined in 20 normal volunteers in four conditions: walking on a treadmill (1) with unrestrained natural arm swing (Normal), (2) while volitionally holding the arms still (Held), (3) with the arms immobilized (Bound), and (4) with the arms swinging in phase with the ipsilateral legs, i.e. opposite-to-normal phasing (Anti-Normal). Normal arm swing involved weak rhythmical lengthening and shortening contractions of arm and shoulder muscles. Phasic muscle activity was needed to keep the unrestricted arms still during walking (Held), indicating a passive component of arm swing. An active component, possibly programmed centrally, existed as well, because some EMG signals persisted when the arms were immobilized during walking (Bound). Anti-Normal gait involved stronger EMG activity than Normal walking and was uneconomical. The present results indicate that normal arm swing has both passive and active components. Copyright © 2011 Elsevier Ltd. All rights reserved.

Deletions of VCX-A and NLGN4: A Variable Phenotype Including Normal Intellect

ERIC Educational Resources Information Center

Macarov, M.; Zeigler, M.; Newman, J. P.; Strich, D.; Sury, V.; Tennenbaum, A.; Meiner, V.

2007-01-01

Background: Patients with Xp22.3 interstitial and terminal deletions have been shown to be affected by intellectual disability (ID) or autism. Previously, "VCX-A" (variably charged protein X-A), located at Xp22.3, was introduced as a gene for ID and its presence was suggested to be sufficient to maintain normal mental development. Recent reports…

Mediating Effect of Body Image Distortion on Weight Loss Efforts in Normal-Weight and Underweight Korean Adolescent Girls

ERIC Educational Resources Information Center

Choi, Jeong-Sil; Kim, Ji-Soo

2017-01-01

Background: We explored the relationship between body mass index-for-age percentile, body image distortion, and unnecessary weight loss efforts in Korean adolescent girls who are underweight and normal weight and examined the mediating effect of body image distortion on weight loss efforts. Methods: This study used data from the 2013 Korea Youth…

Highly sensitive and quantitative detection of rare pathogens through agarose droplet microfluidic emulsion PCR at the single-cell level.

PubMed

Zhu, Zhi; Zhang, Wenhua; Leng, Xuefei; Zhang, Mingxia; Guan, Zhichao; Lu, Jiangquan; Yang, Chaoyong James

2012-10-21

Genetic alternations can serve as highly specific biomarkers to distinguish fatal bacteria or cancer cells from their normal counterparts. However, these mutations normally exist in very rare amount in the presence of a large excess of non-mutated analogs. Taking the notorious pathogen E. coli O157:H7 as the target analyte, we have developed an agarose droplet-based microfluidic ePCR method for highly sensitive, specific and quantitative detection of rare pathogens in the high background of normal bacteria. Massively parallel singleplex and multiplex PCR at the single-cell level in agarose droplets have been successfully established. Moreover, we challenged the system with rare pathogen detection and realized the sensitive and quantitative analysis of a single E. coli O157:H7 cell in the high background of 100,000 excess normal K12 cells. For the first time, we demonstrated rare pathogen detection through agarose droplet microfluidic ePCR. Such a multiplex single-cell agarose droplet amplification method enables ultra-high throughput and multi-parameter genetic analysis of large population of cells at the single-cell level to uncover the stochastic variations in biological systems.

Production and characterization of murine models of classic and intermediate maple syrup urine disease

PubMed Central

Homanics, Gregg E; Skvorak, Kristen; Ferguson, Carolyn; Watkins, Simon; Paul, Harbhajan S

2006-01-01

Background Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of branched-chain keto acid dehydrogenase. MSUD has several clinical phenotypes depending on the degree of enzyme deficiency. Current treatments are not satisfactory and require new approaches to combat this disease. A major hurdle in developing new treatments has been the lack of a suitable animal model. Methods To create a murine model of classic MSUD, we used gene targeting and embryonic stem cell technologies to create a mouse line that lacked a functional E2 subunit gene of branched-chain keto acid dehydrogenase. To create a murine model of intermediate MSUD, we used transgenic technology to express a human E2 cDNA on the knockout background. Mice of both models were characterized at the molecular, biochemical, and whole animal levels. Results By disrupting the E2 subunit gene of branched-chain keto acid dehydrogenase, we created a gene knockout mouse model of classic MSUD. The homozygous knockout mice lacked branched-chain keto acid dehydrogenase activity, E2 immunoreactivity, and had a 3-fold increase in circulating branched-chain amino acids. These metabolic derangements resulted in neonatal lethality. Transgenic expression of a human E2 cDNA in the liver of the E2 knockout animals produced a model of intermediate MSUD. Branched-chain keto acid dehydrogenase activity was 5–6% of normal and was sufficient to allow survival, but was insufficient to normalize circulating branched-chain amino acids levels, which were intermediate between wildtype and the classic MSUD mouse model. Conclusion These mice represent important animal models that closely approximate the phenotype of humans with the classic and intermediate forms of MSUD. These animals provide useful models to further characterize the pathogenesis of MSUD, as well as models to test novel therapeutic strategies, such as gene and cellular therapies, to treat this devastating metabolic disease. PMID:16579849

Road Traffic Accident Victims’ Experiences of Return to Normal Life: A Qualitative Study

PubMed Central

Pashaei Sabet, Fatemeh; Norouzi Tabrizi, Kian; Khankeh, Hamid Reza; Saadat, Soheil; Abedi, Heidar Ali; Bastami, Alireza

2016-01-01

Background Road traffic accident (RTA) victims also suffer from different types of injuries and disabilities, which can affect their quality of life. They usually face with various physical, mental, and social problems. Most traffic accident victims had difficulty to return to normal life. Objectives This study aimed to understand the experiences of return to normal life in RTA victims. Patients and Methods This qualitative study with content analysis approach was conducted on 18 Iranian patients with disability in the upper or lower limbs caused by traffic accidents, who had passed a time between 3 months till 2 years. A purposeful sampling method was applied until reaching data saturation. Data were collected using semi-structured interviews. Afterwards, the gathered data were analyzed through conventional content analysis. Results By analyzing 498 primary codes, four main categories, including supportive needs, adaptation to the new situation, seeking information, and transition from functional limitation, were extracted from traffic accident victims’ experiences of reintegration to normal life. Conclusions The results of this study may help policy-makers to take steps toward health promotion and recovery of RTA victims. Considering the results of this study, it is a need for further research to investigate RTAs victims’ needs for reintegration to home and community. Access to training and supportive facilities like strong therapeutic, nursing and social support, and the possibility to participate in self-care activities is essential for reintegration to community in RTA victims. PMID:27275399

The impact of different background noises: effects on cognitive performance and perceived disturbance in employees with aided hearing impairment and normal hearing.

PubMed

Hua, Håkan; Emilsson, Magnus; Kähäri, Kim; Widén, Stephen; Möller, Claes; Lyxell, Björn

2014-10-01

Health care professionals frequently meet employees with hearing impairment (HI) who experience difficulties at work. There are indications that the majority of these difficulties might be related to the presence of background noise. Moreover, research has also shown that high-level noise has a more detrimental effect on cognitive performance and self-rated disturbance in individuals with HI than low-level noise. The purpose of this study was to examine the impact of different types of background noise on cognitive performance and perceived disturbance (PD) in employees with aided HI and normal hearing. A mixed factorial design was conducted to examine the effect of noise in four experimental conditions. A total of 40 participants (21 men and 19 women) were recruited to take part in the study. The study sample consisted of employees with HI (n = 20) and normal hearing (n = 20). The group with HI had a mild-moderate sensorineural HI, and they were all frequent hearing-aid users. The current study was conducted by using four general work-related tasks (mental arithmetic, orthographic decoding, phonological decoding, and serial recall) in four different background conditions: (1) quiet, (2) office noise at 56 dBA, (3) daycare noise at 73.5 dBA, and (4) traffic noise at 72.5 dBA. Reaction time and the proportion of correct answers in the working tasks were used as outcome measures of cognitive performance. The Borg CR-10 scale was used to assess PD. Data collection occurred on two separate sessions, completed within 4 wk of each other. All tasks and experimental conditions were used in a counterbalanced order. Two-way analysis of variance with repeated measures was performed to analyze the results. To examine interaction effects, pairwise t-tests were used. Pearson correlation coefficients between reaction time and proportion of correct answers, and cognitive performance and PD were also calculated to examine the possible correlation between the different variables. No significant between-group or within-group differences in cognitive performance were observed across the four background conditions. Ratings of PD showed that both groups rated PD according to noise level, where higher noise level generated a higher PD. The present findings also demonstrated that the group with HI was more disturbed by higher than lower levels of noise (i.e., traffic and daycare setting compared with office setting). This pattern was observed consistently throughout four working tasks where the group with HI reported a significantly greater PD in the daycare and traffic settings compared with office noise. The present results demonstrate that background noise does not impair cognitive performance in nonauditory tasks in employees with HI and normal hearing, but that PD is affected to a greater extent in employees with HI during higher levels of background noise exposure. In addition, this study also supports previous studies regarding the detrimental effects that high-level noise has on employees with HI. Therefore, we emphasize the need of both self-rated and cognitive measurements in hearing care and occupational health services for both employees with normal hearing and HI. American Academy of Audiology.

Glenohumeral Function of the Long Head of the Biceps Muscle

PubMed Central

Chalmers, Peter N.; Cip, Johannes; Trombley, Robert; Cole, Brian J.; Wimmer, Markus A.; Romeo, Anthony A.; Verma, Nikhil N.

2014-01-01

Background: Optimal treatment of superior labral anterior-posterior (SLAP) tears is controversial, in part because the dynamic role of the long head of the biceps muscle (LHBM) in the glenohumeral joint is unclear. The aim of this study was to determine dynamic LHBM behavior during shoulder activity by studying (1) the electromyographic activity of the LHBM during shoulder motion, (2) the effect of elbow immobilization on this activity, and (3) the effect of a load applied to the distal humerus on this activity. Hypothesis: The LHBM would not play a significant role in active glenohumeral range of motion. Study Design: Controlled laboratory study. Methods: Thirteen normal volunteers underwent surface electromyography (EMG) measurement of the LHBM, short head biceps muscle (SHBM), deltoid, infraspinatus, and brachioradialis during shoulder motion from the neutral position (0° of rotation, flexion, and abduction) to 45° of flexion, 90° of flexion, 45° of abduction, and 90° of abduction. These motions were repeated both with and without splint immobilization of the forearm and elbow at 100° of flexion and neutral rotation and with and without a 1-kg weight placed on the lateral distal humerus. Results: Mean EMG activity within the LHBM and the SHBM was low (≤11.6% ± 9.1%). LHBM activity was significant increased by flexion and abduction (P < .049 in all cases), while SHBM activity was not. EMG activity from the middle head of the deltoid was significantly increased by loading with the shoulder positioned away from the body (ie, in abduction or flexion). When compared with the unloaded state, the addition of a distal humeral load significantly increased LHBM activity in 45° of abduction (P = .028) and 90° of flexion (P = .033) despite forearm and elbow immobilization. The SHBM showed similar trends. Conclusion: In normal volunteers with forearm and elbow immobilization and application of a load to the distal humerus, LHBM EMG activity is increased by both glenohumeral flexion and abduction, suggesting that this muscle plays a dynamic role in glenohumeral motion with higher demand activities. Clinical Relevance: Biceps tenodesis may result in dynamic change within the glenohumeral joint with higher demand activities. PMID:26535304

Physiological changes, sleep, and morning mood in an isolated environment

NASA Technical Reports Server (NTRS)

Kraft, Norbert O.; Inoue, Natsuhiko; Mizuno, Koh; Ohshima, Hiroshi; Murai, Tadashi; Sekiguchi, Chiharu; Orasanu, J. M. (Principal Investigator)

2002-01-01

BACKGROUND: Previous isolation studies have shown increased 24-h urine volumes and body weight gains in subjects. This project examined those and other physiological variables in relationship to sleep motor activity, subjective sleep quality, mood, and complaints during confinement. METHODS: Six male and two female subjects lived for 7 d in the National Space Development Agency of Japan's isolation chamber, which simulates the interior of the Japanese Experiment Module. Each 24-h period included 6 h of sleep, 3 meals, and 20 min of exercise. Each morning, subjects completed Sleep Sensation and Complaint Index questionnaires. Catecholamine and creatinine excretion, urine volume, and body weight were measured on the 2 d before and 2 d after confinement, and sleep motor activity was measured during confinement. RESULTS: Confinement produced no significant change in body weight, urine volume, or questionnaire results. In contrast, epinephrine, norepinephrine, and sleep motor activity exhibited significant differences during confinement (p < 0.05). Higher nocturnal norepinephrine excretion correlated with higher sleep motor activity. CONCLUSION: The 24-h epinephrine values were slightly higher than normal throughout the experiment, but lower than for subjects working under time-stress. High sympathetic activity (as indicated by norepinephrine) may have interfered with sleep.

Cerebellar Expression of Copper Chaperone for Superoxide, Cytosolic Cu/Zn-Superoxide Dismutase, 4-Hydroxy-2-Nonenal, Acrolein and Heat Shock Protein 32 in Patients with Menkes Kinky Hair Disease: Immunohistochemical Study

PubMed Central

Yokoyama, Atsushi; Ohno, Kousaku; Hirano, Asao; Shintaku, Masayuki; Kato, Masako; Hayashi, Kazuhiko; Kato, Shinsuke

2014-01-01

Background To clarify the pathogenesis of cerebellar Purkinje cell death in patients with Menkes kinky hair disease (MD), a disorder of copper absorption, we investigated the morphological and functional abnormalities of residual Purkinje cells in MD patients and the mechanism of cell death. Methods Seven MD patients and 39 neurologically normal autopsy cases were studied. We performed histopathological and quantitative analyses of the Purkinje cells. In addition, we used immunohistochemistry to detect copper-dependent enzymes [cytosolic Cu/Zn-superoxide dismutase (SOD1) and copper chaperone for superoxide dismutase (CCS)], oxidative stress markers [4-hydroxy-2-nonenal (HNE) and acrolein] and heat shock protein 32 (hsp 32). Results The surviving MD Purkinje cells showed abnormal development, such as somatic sprouts and heterotopic location. Due to maldevelopment and degeneration, dendrites showed the cactus and weeping willow patterns. Axonal degeneration led to the formation of torpedoes. Quantitative analysis revealed loss of approximately 50% of the Purkinje cells in MD patients. Almost all of the normal Purkinje cells were positive for immunostaining by anti-CCS and anti-SOD1 antibodies, with staining of the cell bodies, dendrites and axons. Normal Purkinje cells were not stained by antibodies for HNE, acrolein or hsp 32. In MD patients, the majority of Purkinje cells were positive for CCS, but the positive rate for SOD1 was only about 23%. Approximately 56%, 42% and 40% of the Purkinje cells of MD patients were positive for HNE, acrolein and hsp 32, respectively. Conclusion In MD patients, about 50% of the Purkinje cells have been lost due to maldevelopment and degeneration. In the residual Purkinje cells, CCS expression seems to be nearly normal as a protective response to decreased SOD1 activity due to copper deficiency. Because oxidative stress is elevated secondary to decreased SOD1 activity, hsp 32 is induced as another protective mechanism. PMID:25067875

Characterization of a Lignified Secondary Phloem Fibre‐deficient Mutant of Jute (Corchorus capsularis)

PubMed Central

SENGUPTA, GARGI; PALIT, P.

2004-01-01

• Background and Aims High lignin content of lignocellulose jute fibre does not favour its utilization in making finer fabrics and other value‐added products. To aid the development of low‐lignin jute fibre, this study aimed to identify a phloem fibre mutant with reduced lignin. • Methods An x‐ray‐induced mutant line (CMU) of jute (Corchorus capsularis) was morphologically evaluated and the accession (CMU 013) with the most undulated phenotype was compared with its normal parent (JRC 212) for its growth, secondary fibre development and lignification of the fibre cell wall. • Key Results The normal and mutant plants showed similar leaf photosynthetic rates. The mutant grew more slowly, had shorter internodes and yielded much less fibre after retting. The fibre of the mutant contained 50 % less lignin but comparatively more cellulose than that of the normal type. Differentiation of primary and secondary vascular tissues throughout the CMU 013 stem was regular but it did not have secondary phloem fibre bundles as in JRC 212. Instead, a few thin‐walled, less lignified fibre cells formed uni‐ or biseriate radial rows within the phloem wedges of the middle stem. The lower and earliest developed part of the mutant stem had no lignified fibre cells. This developmental deficiency in lignification of fibre cells was correlated to a similar deficiency in phenylalanine ammonia lyase activity, but not peroxidase activity, in the bark tissue along the stem axis. In spite of severe reduction in lignin synthesis in the phloem cells this mutant functioned normally and bred true. • Conclusions In view of the observations made, the mutant is designated as deficient lignified phloem fibre (dlpf). This mutant may be utilized to engineer low‐lignin jute fibre strains and may also serve as a model to study the positional information that coordinates secondary wall thickening of fibre cells. PMID:14707004

Normal Muscle Oxygen Consumption and Fatigability in Sickle Cell Patients Despite Reduced Microvascular Oxygenation and Hemorheological Abnormalities

PubMed Central

Waltz, Xavier; Pichon, Aurélien; Lemonne, Nathalie; Mougenel, Danièle; Lalanne-Mistrih, Marie-Laure; Lamarre, Yann; Tarer, Vanessa; Tressières, Benoit; Etienne-Julan, Maryse; Hardy-Dessources, Marie-Dominique; Hue, Olivier; Connes, Philippe

2012-01-01

Background/Aim Although it has been hypothesized that muscle metabolism and fatigability could be impaired in sickle cell patients, no study has addressed this issue. Methods We compared muscle metabolism and function (muscle microvascular oxygenation, microvascular blood flow, muscle oxygen consumption and muscle microvascular oxygenation variability, which reflects vasomotion activity, maximal muscle force and local muscle fatigability) and the hemorheological profile at rest between 16 healthy subjects (AA), 20 sickle cell-hemoglobin C disease (SC) patients and 16 sickle cell anemia (SS) patients. Results Muscle microvascular oxygenation was reduced in SS patients compared to the SC and AA groups and this reduction was not related to hemorhelogical abnormalities. No difference was observed between the three groups for oxygen consumption and vasomotion activity. Muscle microvascular blood flow was higher in SS patients compared to the AA group, and tended to be higher compared to the SC group. Multivariate analysis revealed that muscle oxygen consumption was independently associated with muscle microvascular blood flow in the two sickle cell groups (SC and SS). Finally, despite reduced muscle force in sickle cell patients, their local muscle fatigability was similar to that of the healthy subjects. Conclusions Sickle cell patients have normal resting muscle oxygen consumption and fatigability despite hemorheological alterations and, for SS patients only, reduced muscle microvascular oxygenation and increased microvascular blood flow. Two alternative mechanisms can be proposed for SS patients: 1) the increased muscle microvascular blood flow is a way to compensate for the lower muscle microvascular oxygenation to maintain muscle oxygen consumption to normal values or 2) the reduced microvascular oxygenation coupled with a normal resting muscle oxygen consumption could indicate that there is slight hypoxia within the muscle which is not sufficient to limit mitochondrial respiration but increases muscle microvascular blood flow. PMID:23285055

GASTRIC AND JEJUNAL HISTOPATHOLOGICAL CHANGES IN PATIENTS UNDERGOING BARIATRIC SURGERY

PubMed Central

RODRIGUES, Rosemary Simões Nomelini; ALMEIDA, Élia Cláudia de Souza; CAMILO, Silvia Maria Perrone; TERRA-JÚNIOR, Júverson Alves; GUIMARÃES, Lucinda Calheiros; DUQUE, Ana Cristina da Rocha; ETCHEBEHERE, Renata Margarida

2016-01-01

ABSTRACT Background: Morbid obesity is a multifactorial disease that increasingly is being treated by surgery. Aim: To evaluate gastric histopathological changes in obese, and to compare with patients who underwent gastrojejunal bypass and the jejunal mucosa after the surgery. Methods: This is an observational study performed at a tertiary public hospital, evaluating endoscopic biopsies from 36 preoperative patients and 35 postoperative. Results: In the preoperative group, 80.6% had chronic gastritis, which was active in 38.9% (77.1% and 20.1%, respectively, in the postoperative). The postoperative group had a significant reduction in H. pylori infection (p=0.0001). A longer length of the gastric stump and a time since surgery of more than two years were associated with Helicobacter pylori infection. The jejunal mucosa was normal in 91.4% and showed slight nonspecific chronic inflammation in 8.6%. Conclusion: There was a reduction in the incidence of Helicobacter pylori infection in the postoperative group. A longer length of the gastric stump and longer time elapsed since surgery were associated with Helicobacter pylori infection. The jejunal mucosa was considered normal in an absolute majority of patients. PMID:27683773

On gray dancing: Constructions of age-normality through choreography and temporal codes.

PubMed

Krekula, Clary; Arvidson, Markus; Heikkinen, Satu; Henriksson, Andreas; Olsson, Eva

2017-08-01

Against the background of population aging, older peoples dance has attracted attention in research and its health promoting effects and social meanings have been brought to the fore. In this article we focus on the context and power dimensions of dance with an emphasis on the organizing of dance among older adults in terms of social discourses and age relationships. On the basis of qualitative interviews with 33 older dancers and 11 dance providers in Sweden, the study illustrates how dance is organized through social discourses on healthism and on the increasing group of older people as a powerful consumer group. The study highlights that older people and their social dance contexts are marked and subordinated in relation to younger age groups through non-verbal practices such as choreography and temporal codes. In short, dancing among older adults is not only a common health promoting and social activity, but also an arena in which age and age normality are negotiated and constructed. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

RESIDENTIAL EXPOSURE TO EXTREMELY LOW FREQUENCY ELECTRIC AND MAGNETIC FIELDS IN THE CITY OF RAMALLAH-PALESTINE.

PubMed

Abuasbi, Falastine; Lahham, Adnan; Abdel-Raziq, Issam Rashid

2018-04-01

This study was focused on the measurement of residential exposure to power frequency (50-Hz) electric and magnetic fields in the city of Ramallah-Palestine. A group of 32 semi-randomly selected residences distributed amongst the city were under investigations of fields variations. Measurements were performed with the Spectrum Analyzer NF-5035 and were carried out at one meter above ground level in the residence's bedroom or living room under both zero and normal-power conditions. Fields' variations were recorded over 6-min and some times over few hours. Electric fields under normal-power use were relatively low; ~59% of residences experienced mean electric fields <10 V/m. The highest mean electric field of 66.9 V/m was found at residence R27. However, electric field values were log-normally distributed with geometric mean and geometric standard deviation of 9.6 and 3.5 V/m, respectively. Background electric fields measured under zero-power use, were very low; ~80% of residences experienced background electric fields <1 V/m. Under normal-power use, the highest mean magnetic field (0.45 μT) was found at residence R26 where an indoor power substation exists. However, ~81% of residences experienced mean magnetic fields <0.1 μT. Magnetic fields measured inside the 32 residences showed also a log-normal distribution with geometric mean and geometric standard deviation of 0.04 and 3.14 μT, respectively. Under zero-power conditions, ~7% of residences experienced average background magnetic field >0.1 μT. Fields from appliances showed a maximum mean electric field of 67.4 V/m from hair dryer, and maximum mean magnetic field of 13.7 μT from microwave oven. However, no single result surpassed the ICNIRP limits for general public exposures to ELF fields, but still, the interval 0.3-0.4 μT for possible non-thermal health impacts of exposure to ELF magnetic fields, was experienced in 13% of the residences.

The Binding Problem for Syntax, Semantics, and Prosody: H.M.'s Selective Sentence-Reading Deficits under the Theoretical-Syndrome Approach.

ERIC Educational Resources Information Center

MacKay, Donald G.; James, Lori E.

2001-01-01

A "hippocampal amnesiac" (H.M.) and memory-normal controls of similar age, background, intelligence, and education read novel sentences aloud in tasks where fast and accurate reading was or was not the primary goal. H.M produced more misreadings than normal and cerebellar controls, usually without self-correction. Results support a theoretical…

The ERP research about the influence of the music of Chopin on working memory

NASA Astrophysics Data System (ADS)

Sun, C. A.; Wei, Hong-tao; Yue, Li-juan

2011-10-01

This study is to examine the effect of the music of Chopin on working memory and the electrical activity of the brain in different conditions by using event-related potentials (ERPs), adopting n-back experimental paradigm and to study the neuromechanism. Thirty adults performed behavioral experiments with three conditions of music and two levels of n-back task. Fourteen normal adults performed ERP experiments with the same program as the behavioral experiment and the EEG were recorded. Chopin music improved people's working memory and pilot music improved most effectively.P3 peak amplitude decreased as working memory load increased. Especially in high load task, P3 peak amplitude decreased gradually in pilot music, background music and free music condition.

Preliminary results utilizing high-energy fission product γ-rays to detect fissionable material in cargo

NASA Astrophysics Data System (ADS)

Slaughter, D. R.; Accatino, M. R.; Bernstein, A.; Church, J. A.; Descalle, M. A.; Gosnell, T. B.; Hall, J. M.; Loshak, A.; Manatt, D. R.; Mauger, G. J.; Moore, T. L.; Norman, E. B.; Pohl, B. A.; Pruet, J. A.; Petersen, D. C.; Walling, R. S.; Weirup, D. L.; Prussin, S. G.; McDowell, M.

2005-12-01

A concept for detecting the presence of special nuclear material (235U or 239Pu) concealed in intermodal cargo containers is described. It is based on interrogation with a pulsed beam of 7 MeV neutrons that produce fission events and their β-delayed neutron emission or β-delayed high-energy γ radiation between beam pulses provide the detection signature. Fission product β-delayed γ-rays above 3 MeV are nearly 10 times more abundant than β-delayed neutrons and are distinct from natural radioactivity and from nearly all of the induced activity in a normal cargo. Detector backgrounds and potential interferences with the fission signature radiation have been identified and quantified.

Neural-Thyroid Interaction on Skeletal Isomyosin in Zero Gravity

NASA Technical Reports Server (NTRS)

Baldwin, Kenneth M.

2000-01-01

The primary goal of the project was to develop a ground based model to first study the role of the nerve and of thyroid hormone (T3) in the regulation of body growth and skeletal muscle growth and differentiation in rodents. A primary objective was to test the hypothesis that normal weight bearing activity is essential for the development of antigravity, slow twitch skeletal muscle and the corresponding slow myosin heavy chain (MHC) gene; whereas, T3 was obligatory for general body and muscle growth and the establishment of fast MHC phenotype in typically fast locomoter muscles. These ground based experiments would provide both the efficacy and background for a spaceflight experiment (referred to as the Neurolab Mission) jointly sponsored by the NIH and NASA.

Deep Extragalactic X-Ray Surveys

NASA Astrophysics Data System (ADS)

Brandt, W. N.; Hasinger, G.

2005-09-01

Deep surveys of the cosmic X-ray background are reviewed in the context of observational progress enabled by the Chandra X-Ray Observatory and the X-Ray Multi-Mirror Mission-Newton. The sources found by deep surveys are described along with their redshift and luminosity distributions, and the effectiveness of such surveys at selecting active galactic nuclei (AGN) is assessed. Some key results from deep surveys are highlighted, including (a) measurements of AGN evolution and the growth of supermassive black holes, (b) constraints on the demography and physics of high-redshift AGN, (c) the X-ray AGN content of infrared and submillimeter galaxies, and (d) X-ray emission from distant starburst and normal galaxies. We also describe some outstanding problems and future prospects for deep extragalactic X-ray surveys.

Current strategies with 1-stage prosthetic breast reconstruction

PubMed Central

2015-01-01

Background 1-stage prosthetic breast reconstruction is gaining traction as a preferred method of breast reconstruction in select patients who undergo mastectomy for cancer or prevention. Methods Critical elements to the procedure including patient selection, technique, surgical judgment, and postoperative care were reviewed. Results Outcomes series reveal that in properly selected patients, direct-to-implant (DTI) reconstruction has similar low rates of complications and high rates of patient satisfaction compared to traditional 2-stage reconstruction. Conclusions 1-stage prosthetic breast reconstruction may be the procedure of choice in select patients undergoing mastectomy. Advantages include the potential for the entire reconstructive process to be complete in one surgery, the quick return to normal activities, and lack of donor site morbidity. PMID:26005643

Defeating camouflage and finding explosives through spectral matched filtering of hyperspectral imagery

NASA Astrophysics Data System (ADS)

Dombrowski, Mark S.; Willson, Paul D.; LaBaw, Clayton C.

1997-01-01

In order to achieve their goal of surreptitious operation within a country, terrorist organizations attempt to hide themselves from public view. In many instances such masking takes the form of simply appearing like the surrounding populace. In others, such as training facilities, standard military camouflaging techniques are used to conceal the group's equipment and activities. To effectively monitor and suppress activities of terrorist organizations, defeating the groups' attempt to hide is essential. Although finding individuals hiding within a society is extremely problematic, discovering camouflaged equipment, facilities, and personnel is readily accomplished by proper exploitation of hyperspectral imagery. Camouflage techniques attempt to make an object appear similar to its background, thereby making it difficult to find. Although making an object have similar color to its background is fairly easy, making it have the same spectral appearance is nearly impossible, unless the object is covered in the same material as the background. Even attempting to hide an object by covering it in background material will not work against a spectral imager since the act of moving the background material, e.g., foliage cuttings, changes the material's spectral characteristics. Hence, by collecting and properly exploiting spectral imagery, camouflaged objects can be readily differentiated from their background. This paper presents development of this technique, and of the MIDIS (multi-band identification and discrimination imaging spectroradiometer) instrument capable of real-time discrimination of camouflaged objects throughout a scene. Spectral matched-filtering of hyperspectral imagery also has the potential to find vehicles or structures which may be laden with explosives. Many explosives contain volatile materials, the release of which can be imaged by viewing appropriate spectral regions. Volatiles from the fuel oil in readily-produced ANFO are an example. If such volatiles were seen emanating from a vehicle or structure where they would not normally be expected, closer inspection would be warranted. Additionally, packing a vehicle with explosives often leaves trace residues on the outside of the vehicle. Spectral imaging and matched filtering can be used to identify these residues. Incorporation of spectral imaging surveillance equipment at probable terrorist targets could avert disasters such as the tragic bombing of the Murrah Federal Building in Oklahoma City. Application of MIDIS technology to explosive identification is also detailed.

Monte Carlo calculation of the maximum therapeutic gain of tumor antivascular alpha therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Chen-Yu; Oborn, Bradley M.; Guatelli, Susanna

Purpose: Metastatic melanoma lesions experienced marked regression after systemic targeted alpha therapy in a phase 1 clinical trial. This unexpected response was ascribed to tumor antivascular alpha therapy (TAVAT), in which effective tumor regression is achieved by killing endothelial cells (ECs) in tumor capillaries and, thus, depriving cancer cells of nutrition and oxygen. The purpose of this paper is to quantitatively analyze the therapeutic efficacy and safety of TAVAT by building up the testing Monte Carlo microdosimetric models. Methods: Geant4 was adapted to simulate the spatial nonuniform distribution of the alpha emitter {sup 213}Bi. The intraluminal model was designed tomore » simulate the background dose to normal tissue capillary ECs from the nontargeted activity in the blood. The perivascular model calculates the EC dose from the activity bound to the perivascular cancer cells. The key parameters are the probability of an alpha particle traversing an EC nucleus, the energy deposition, the lineal energy transfer, and the specific energy. These results were then applied to interpret the clinical trial. Cell survival rate and therapeutic gain were determined. Results: The specific energy for an alpha particle hitting an EC nucleus in the intraluminal and perivascular models is 0.35 and 0.37 Gy, respectively. As the average probability of traversal in these models is 2.7% and 1.1%, the mean specific energy per decay drops to 1.0 cGy and 0.4 cGy, which demonstrates that the source distribution has a significant impact on the dose. Using the melanoma clinical trial activity of 25 mCi, the dose to tumor EC nucleus is found to be 3.2 Gy and to a normal capillary EC nucleus to be 1.8 cGy. These data give a maximum therapeutic gain of about 180 and validate the TAVAT concept. Conclusions: TAVAT can deliver a cytotoxic dose to tumor capillaries without being toxic to normal tissue capillaries.« less

Foot Pain and Pronated Foot Type are Associated with Self-Reported Mobility Limitations in Older Adults: the Framingham Foot Study

PubMed Central

Menz, Hylton B.; Dufour, Alyssa B.; Katz, Patricia; Hannan, Marian T.

2015-01-01

Background The foot plays an important role in supporting the body when undertaking weight bearing activities. Aging is associated with an increased prevalence of foot pain and a lowering of the arch of the foot, both of which may impair mobility. Objective To examine the associations of foot pain, foot posture and dynamic foot function with self-reported mobility limitations in community-dwelling older adults. Methods Foot examinations were conducted on 1,860 members of the Framingham Study in 2002–2005. Foot posture was categorized as normal, planus or cavus using static pressure measurements, and foot function was categorized as normal, pronated or supinated using dynamic pressure measurements. Participants were asked whether they had foot pain and any difficulty performing a list of nine weight bearing tasks. Multivariate logistic regression and linear regression models were used to examine the associations of foot pain, posture, function and ability to perform these activities. Results After adjusting for age, sex, height and weight, foot pain was significantly associated with difficulty performing all nine weight bearing activities. Compared to those with normal foot posture and function, participants with planus foot posture were more likely to report difficulty remaining balanced (odds ratio [OR] = 1.40, 95% confidence interval [CI] 1.06 to 1.85; p=0.018) and individuals with pronated foot function were more likely to report difficulty walking across a small room (OR = 2.07, 95% CI 1.02 to 4.22; p=0.045). Foot pain and planus foot posture were associated with an overall mobility limitation score combining performances on each measure. Conclusion Foot pain, planus foot posture and pronated foot function are associated with self-reported difficulty undertaking common weight bearing tasks. Interventions to reduce foot pain and improve foot posture and function may therefore have a role in improving mobility in older adults. PMID:26645379

Regular Football Practice Improves Autonomic Cardiac Function in Male Children

PubMed Central

Fernandes, Luis; Oliveira, Jose; Soares-Miranda, Luisa; Rebelo, Antonio; Brito, Joao

2015-01-01

Background: The role of the autonomic nervous system (ANS) in the cardiovascular regulation is of primal importance. Since it has been associated with adverse conditions such as cardiac arrhythmias, sudden death, sleep disorders, hypertension and obesity. Objectives: The present study aimed to investigate the impact of recreational football practice on the autonomic cardiac function of male children, as measured by heart rate variability. Patients and Methods: Forty-seven male children aged 9 - 12 years were selected according to their engagement with football oriented practice outside school context. The children were divided into a football group (FG; n = 22) and a control group (CG; n = 25). The FG had regular football practices, with 2 weekly training sessions and occasional weekend matches. The CG was not engaged with any physical activity other than complementary school-based physical education classes. Data from physical activity, physical fitness, and heart rate variability measured in time and frequency domains were obtained. Results: The anthropometric and body composition characteristics were similar in both groups (P > 0.05). The groups were also similar in time spent daily on moderate-to-vigorous physical activities (FG vs. CG: 114 ± 64 vs. 87 ± 55 minutes; P > 0.05). However, the FG performed better (P < 0.05) in Yo-Yo intermittent endurance test (1394 ± 558 vs. 778 ± 408 m) and 15-m sprint test (3.06 ± 0.17 vs. 3.20 ± 0.23 s). Also, the FG presented enhanced autonomic function. Significant differences were detected (P < 0.05) between groups for low frequency normalized units (38.0 ± 15.2 vs. 47.3 ± 14.2 n.u (normalized units)), high frequency normalized units (62.1 ± 15.2 vs. 52.8 ± 14.2 n.u.), and LF:HF ratio (0.7 ± 0.4 vs. 1.1 ± 0.6 ms2). Conclusions: Children engaged with regular football practice presented enhanced physical fitness and autonomic function, by increasing vagal tone at rest. PMID:26448848

Neutrophil depletion in the early inflammatory phase delayed cutaneous wound healing in older rats: improvements due to the use of un-denatured camel whey protein

PubMed Central

2014-01-01

Background While it is known that advanced age alters the recruitment of neutrophils during wound healing, thereby delaying the wound healing process, little is known about prolonged wound healing in advanced ages. Thus, we investigated the correlation of neutrophil recruitment with healing events, and the impact of whey protein (WP) on neutrophil activation. Methods The animals were allocated into wounded young group, wounded older group and wounded older rats with daily treatment of WP at a dose of 100 mg/kg of body weight. Results Our results pointed to a marked deficiency in the number of neutrophils in the wounds of older rats, which was accompanied with impairment of the healing process. In the group of older rats, phagocytic activity, as tested by fluorescence microscopy, declined throughout the first 24 hours after wounding. Both the neutrophil number and the phagocytic activity recovered in older rats which received WP supplementation. Interestingly, WP was found to significantly up-regulate the MIP-1α and CINC-1 mRNA expression in old rats. On the other hand, the wound size in older rats was significantly higher than that in younger ones. Blood angiogenesis was also significantly delayed in the older group as opposed to the young rats. WP, however, was found to return these indices to normal levels in the older rats. Proliferation and epidermal migration of the keratinocytes and the collagen deposition were also returned to the normal rates. Conclusions This data confirms the critical role of neutrophil recruitment in the early inflammatory phase of wound healing in older rats. In addition, WP protein was used to improve neutrophil function in older rats, healing events returned to a more normal profile. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2100966986117779. PMID:24593823

The January 2006 Volcanic-Tectonic Earthquake Swarm at Mount Martin, Alaska

USGS Publications Warehouse

Dixon, James P.; Power, John A.

2009-01-01

On January 8, 2006, a swarm of volcanic-tectonic earthquakes began beneath Mount Martin at the southern end of the Katmai volcanic cluster. This was the first recorded swarm at Mount Martin since continuous seismic monitoring began in 1996. The number of located earthquakes increased during the next four days, reaching a peak on January 11. For the next two days, the seismic activity decreased, and on January 14, the number of events increased to twice the previous day's total. Following this increase in activity, seismicity declined, returning to background levels by the end of the month. The Alaska Volcano Observatory located 860 earthquakes near Mount Martin during January 2006. No additional signs of volcanic unrest were noted in association with this earthquake swarm. The earthquakes in the Mount Martin swarm, relocated using the double difference technique, formed an elongated cluster dipping to the southwest. Focal mechanisms beneath Mount Martin show a mix of normal, thrust, and strike-slip solutions, with normal focal mechanisms dominating. For earthquakes more than 1 km from Mount Martin, all focal mechanisms showed normal faulting. The calculated b-value for the Mount Martin swarm is 0.98 and showed no significant change before, during, or after the swarm. The triggering mechanism for the Mount Martin swarm is unknown. The time-history of earthquake occurrence is indicative of a volcanic cause; however, there were no low-frequency events or observations, such as increased steaming associated with the swarm. During the swarm, there was no change in the b-value, and the distribution and type of focal mechanisms were similar to those in the period before the anomalous activity. The short duration of the swarm, the similarity in observed focal mechanisms, and the lack of additional signs of unrest suggest this swarm did not result from a large influx of magma within the shallow crust beneath Mount Martin.

Background concentrations of metals in soils from selected regions in the State of Washington

USGS Publications Warehouse

Ames, K.C.; Prych, E.A.

1995-01-01

Soil samples from 60 sites in the State of Washington were collected and analyzed to determine the magnitude and variability of background concen- trations of metals in soils of the State. Samples were collected in areas that were relatively undisturbed by human activity from the most pre- dominant soils in 12 different regions that are representative of large areas of Washington State. Concentrations of metals were determined by five different laboratory methods. Concentrations of mercury and nickel determined by both the total and total-recoverable methods displayed the greatest variability, followed by chromium and copper determined by the total-recoverable method. Concentrations of other metals, such as aluminum and barium determined by the total method, varied less. Most metals concentrations were found to be more nearly log-normally than normally distributed. Total metals concentrations were not significantly different among the different regions. However, total-recoverable metals concentrations were not as similar among different regions. Cluster analysis revealed that sampling sites in three regions encompassing the Puget Sound could be regrouped to form two new regions and sites in three regions in south-central and southeastern Washington State could also be regrouped into two new regions. Concentrations for 7 of 11 total-recoverable metals correlated with total metals concentrations. Concen- trations of six total metals also correlated positively with organic carbon. Total-recoverable metals concentrations did not correlate with either organic carbon or particle size. Concentrations of metals determined by the leaching methods did not correlate with total or total-recoverable metals concentrations, nor did they correlate with organic carbon or particle size.

Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis

PubMed Central

Honda, Hiroshi; Barrueto, Fermin F; Gogusev, Jean; Im, Dwight D; Morin, Patrice J

2008-01-01

Background Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer. Methods In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues. Results We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis. Conclusion In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis. PMID:19055724

Matrix Stiffness Corresponding to Strictured Bowel Induces a Fibrogenic Response in Human Colonic Fibroblasts

PubMed Central

Johnson, Laura A.; Rodansky, Eva S.; Sauder, Kay L.; Horowitz, Jeffrey C.; Mih, Justin D.; Tschumperlin, Daniel J.; Higgins, Peter D.

2013-01-01

Background Crohn’s disease is characterized by repeated cycles of inflammation and mucosal healing which ultimately progress to intestinal fibrosis. This inexorable progression towards fibrosis suggests that fibrosis becomes inflammation-independent and auto-propagative. We hypothesized that matrix stiffness regulates this auto-propagation of intestinal fibrosis. Methods The stiffness of fresh ex vivo samples from normal human small intestine, Crohn’s disease strictures, and the unaffected margin were measured with a microelastometer. Normal human colonic fibroblasts were cultured on physiologically normal or pathologically stiff matrices corresponding to the physiological stiffness of normal or fibrotic bowel. Cellular response was assayed for changes in cell morphology, α-smooth muscle actin (αSMA) staining, and gene expression. Results Microelastometer measurements revealed a significant increase in colonic tissue stiffness between normal human colon and Crohn’s strictures as well as between the stricture and adjacent tissue margin. In Ccd-18co cells grown on stiff matrices corresponding to Crohn’s strictures, cellular proliferation increased. Pathologic stiffness induced a marked change in cell morphology and increased αSMA protein expression. Growth on a stiff matrix induced fibrogenic gene expression, decreased matrix metalloproteinase and pro-inflammatory gene expression, and was associated with nuclear localization of the transcriptional cofactor MRTF-A. Conclusions Matrix stiffness, representative of the pathological stiffness of Crohn’s strictures, activates human colonic fibroblasts to a fibrogenic phenotype. Matrix stiffness affects multiple pathways suggesting the mechanical properties of the cellular environment are critical to fibroblast function and may contribute to autopropagation of intestinal fibrosis in the absence of inflammation, thereby contributing to the intractable intestinal fibrosis characteristic of Crohn’s disease. PMID:23502354

Cardiac Strain between Normal Weight and Overweight Workers in Hot/Humid Weather in the Persian Gulf

PubMed Central

Dehghan, Habibollah; Mortazavi, Seyed Bagher; Jafari, Mohammad Javad; Maracy, Mohammad Reza

2013-01-01

Background: In hot weather, overweight and obesity are considered as significant risk factors for the incidence of cardiac strain in workers. This study was aimed to compare cardiac strain among overweight and normal-weight workers in hot, humid conditions in the south of Iran. Methods: This cross-sectional study was conducted on 71 workers in the south of Iran in summer 2010. The heart rate was measured at rest and at actual work. Cardiac strain based on working heart rate (WHR), the relative cardiac cost (RCC), the net cardiac cost (NCC), load relative cardiovascular (CVL), and heart rate reduction was analyzed in 35 normal-weight people (body mass index (BMI) <25 kg/m2) and 36 overweight people (BMI >25 kg/m2) using descriptive statistics. Results: In 42% of the total workers, BMI was >25 kg/m2. The average of Wet Bulb Globe Temperature Index (WBGT Index) in the two groups was not significantly different. The mean WHR in the two groups was 101 ± 20.3 and 112 ± 18.9, respectively (P = 0.026). Percentages exceeded the acceptable limits in the parameters NCC, RCC, WHR, CVL, and Brouha index, which were significantly higher in overweight people than in those with normal weight. Conclusions: Based on the study results, it is concluded that the severity of cardiac strain was higher in overweight workers compared with that in normal weight workers. Hence, in order to decrease the cardiac strain, selecting overweight individuals for these jobs should be avoided and also some vital intervention for losing weight should be implemented such as nutrition education and encouraging them regarding physical activity. PMID:24319554

Gravitoinertial force level influences arm movement control

NASA Technical Reports Server (NTRS)

Fisk, J.; Lackner, J. R.; DiZio, P.

1993-01-01

1. The ability to move the forearm between remembered elbow joint angles immediately after rapid increases or decreases of the background gravitoinertial force (G) level was measured. The movements had been well-practiced in a normal 1G environment before the measurements in high-(1.8G) and low-force (0G) environments. The forearm and upper arm were always unsupported to maximize the influence of altered G-loading and to minimize extraneous cues about arm position. 2. Horizontal and vertical movement planes were studied to measure the effects of varying the G load in the movement plane within a given G background. Rapid and slow movements were studied to assess the role of proprioceptive feedback. 3. G level did not affect the amplitude of rapid movements, indicating that subjects were able to plan and to generate appropriate motor commands for the new G loading of the arm. The amplitude of slow movements was affected by G level, indicating that proprioceptive feedback is influenced by G level. 4. The effects of G level were similar for horizontal and vertical movements, indicating that proprioceptive information from supporting structures, such as the shoulder joint and muscles, had a role in allowing generation of the appropriate motor commands. 5. The incidence and size of dynamic overshoots were greater in 0G and for rapid movements. This G-related change in damping suggests a decrease in muscle spindle activity in 0G. A decrease in muscle spindle activity in 0G and an increase in 1.8G are consistent with the results of our prior studies on the tonic vibration reflex, locomotion, and perception of head movement trajectory in varying force backgrounds.

Spectral properties and associated plasma energization by magnetosonic waves in the Earth's magnetosphere: Particle-in-cell simulations

NASA Astrophysics Data System (ADS)

Sun, Jicheng; Gao, Xinliang; Lu, Quanming; Chen, Lunjin; Liu, Xu; Wang, Xueyi; Tao, Xin; Wang, Shui

2017-05-01

In this paper, we perform a 1-D particle-in-cell (PIC) simulation model consisting of three species, cold electrons, cold ions, and energetic ion ring, to investigate spectral structures of magnetosonic waves excited by ring distribution protons in the Earth's magnetosphere, and dynamics of charged particles during the excitation of magnetosonic waves. As the wave normal angle decreases, the spectral range of excited magnetosonic waves becomes broader with upper frequency limit extending beyond the lower hybrid resonant frequency, and the discrete spectra tends to merge into a continuous one. This dependence on wave normal angle is consistent with the linear theory. The effects of magnetosonic waves on the background cold plasma populations also vary with wave normal angle. For exactly perpendicular magnetosonic waves (parallel wave number k|| = 0), there is no energization in the parallel direction for both background cold protons and electrons due to the negligible fluctuating electric field component in the parallel direction. In contrast, the perpendicular energization of background plasmas is rather significant, where cold protons follow unmagnetized motion while cold electrons follow drift motion due to wave electric fields. For magnetosonic waves with a finite k||, there exists a nonnegligible parallel fluctuating electric field, leading to a significant and rapid energization in the parallel direction for cold electrons. These cold electrons can also be efficiently energized in the perpendicular direction due to the interaction with the magnetosonic wave fields in the perpendicular direction. However, cold protons can be only heated in the perpendicular direction, which is likely caused by the higher-order resonances with magnetosonic waves. The potential impacts of magnetosonic waves on the energization of the background cold plasmas in the Earth's inner magnetosphere are also discussed in this paper.

Critical Configuration and Physics Measurements for Beryllium Reflected Assemblies of U(93.15)O₂ Fuel Rods (1.506-cm Pitch and 7-Tube Clusters)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marshall, Margaret A.; Bess, John D.; Briggs, J. Blair

2015-03-01

Cadmium ratios were measured with enriched uranium metal foils at various locations in the assembly with the fuel tube at the 1.506-cm spacing. They are described in the following subsections. The experiment configuration was the same as the first critical configuration described in HEU-COMP-FAST-004 (Case 1). The experimenter placed 0.75-cm-diameter × 0.010-cm-thick 93.15%-235U-enriched uranium metal foils with and without 0.051-cm-thick cadmium covers at various locations in the core and top reflector. One part of the cadmium cover was cupshape and contained the uranium foil. The other part was a lid that fit over the exposed side of the foil whenmore » it was in the cup shaped section of the cover. As can be seen in the logbook, two runs were required to obtain all the measurements necessary for the cadmium ratio. The bare foil measurements within the top reflector were run first as part of the axial foil activation measurements. The results of this run are used for both the axial activation results and the cadmium ratios. Cadmium covered foils were then placed at the same location through the top reflector in a different run. Three pairs of bare and cadmium covered foils were also placed through the core tank. One pair was placed at the axial center of a fuel tube 11.35 cm from the center of the core. Two pairs of foils were placed on top of fuel tubes 3.02 and 12.06 cm from the center of the core. The activation of the uranium metal foils was measured after removal from the assembly using two lead shielded NaI scintillation detectors as follows. The NaI scintillators were carefully matched and had detection efficiencies for counting delayed-fission-product gamma rays with energies above 250 KeV within 5%. In all foil activation measurements, one foil at a specific location was used as a normalizing foil to remove the effects of the decay of fission products during the counting measurements with the NaI detectors. The normalization foil was placed on one NaI scintillator and the other foil on the other NaI detector and the activities measured simultaneously. The activation of a particular foil was compared to that of the normalization foil by dividing the count rate for each foil by that of the normalization foil. To correct for the differing efficiencies of the two NaI detectors, the normalization foil was counted in Detector 1 simultaneously with the foil at position x in Detector 2, and then the normalization foil was counted simultaneously in Detector 2 with the foil from position x in Counter 1. The activity of the foil from position x was divided by the activity of the normalization foil counted simultaneously. This resulted in obtaining two values of the ratio that were then averaged. This procedure essentially removed the effect of the differing efficiencies of the two NaI detectors. Differing efficiencies of 10% resulted in errors in the ratios measured to less than 1%. The background counting rates obatined with the foils used for the measurements on the NaI detectors before their irradiation measurement were subtracted from all count rates. The results of the cadmium ratio measurements are given in Table 1.3-1 and Figure 1.3-1. “No correction has been made for self shielding in the foils” (Reference 3).« less

Stress induction in the bacteria Shewanella oneidensis and Deinococcus radiodurans in response to below-background ionizing radiation.

PubMed

Castillo, Hugo; Schoderbek, Donald; Dulal, Santosh; Escobar, Gabriela; Wood, Jeffrey; Nelson, Roger; Smith, Geoffrey

2015-01-01

The 'Linear no-threshold' (LNT) model predicts that any amount of radiation increases the risk of organisms to accumulate negative effects. Several studies at below background radiation levels (4.5-11.4 nGy h(-1)) show decreased growth rates and an increased susceptibility to oxidative stress. The purpose of our study is to obtain molecular evidence of a stress response in Shewanella oneidensis and Deinococcus radiodurans grown at a gamma dose rate of 0.16 nGy h(-1), about 400 times less than normal background radiation. Bacteria cultures were grown at a dose rate of 0.16 or 71.3 nGy h(-1) gamma irradiation. Total RNA was extracted from samples at early-exponential and stationary phases for the rt-PCR relative quantification (radiation-deprived treatment/background radiation control) of the stress-related genes katB (catalase), recA (recombinase), oxyR (oxidative stress transcriptional regulator), lexA (SOS regulon transcriptional repressor), dnaK (heat shock protein 70) and SOA0154 (putative heavy metal efflux pump). Deprivation of normal levels of radiation caused a reduction in growth of both bacterial species, accompanied by the upregulation of katB, recA, SOA0154 genes in S. oneidensis and the upregulation of dnaK in D. radiodurans. When cells were returned to background radiation levels, growth rates recovered and the stress response dissipated. Our results indicate that below-background levels of radiation inhibited growth and elicited a stress response in two species of bacteria, contrary to the LNT model prediction.

Impact of Age-Dependent Adventitia Inflammation on Structural Alteration of Abdominal Aorta in Hyperlipidemic Mice

PubMed Central

Sakamoto, Sumiharu; Tsuruda, Toshihiro; Hatakeyama, Kinta; Imamura, Takuroh; Asada, Yujiro; Kitamura, Kazuo

2014-01-01

Background The adventitia is suggested to contribute to vascular remodeling; however, the site-selective inflammatory responses in association with the development of atherosclerosis remain to be elucidated. Methods and Results Wild-type or apolipoprotein E knockout male C57BL/6J background mice were fed standard chow for 16, 32, and 52 weeks, and the morphology of the aortic arch, descending aorta, and abdominal aorta was compared. Atheromatous plaque formation progressed with age, particularly in the aortic arch and abdominal aorta but not in the descending aorta. In addition, we found that the numbers of macrophages, T-lymphocytes, and microvessels, assessed by anti-F4/80, CD3, and CD31 antibodies, were higher in the adventitia of the abdominal aorta at 52 weeks. These numbers were positively correlated with plaque formation, but negatively correlated with elastin content, resulting in the enlargement of the total vessel area. In aortic tissues, interleukin-6 levels increased in the atheromatous plaque with age, whereas the level of regulated on activation, normal T cell expressed and secreted (RANTES) increased with age, and compared with other sites, it was particularly distributed in inflammatory cells in the adventitia of the abdominal aorta. Conclusion This study suggests that adventitial inflammation contributes to the age-dependent structural alterations, and that the activation/inactivation of cytokines/chemokines is involved in the process. PMID:25153991

Visual signature reduction of unmanned aerial vehicles

NASA Astrophysics Data System (ADS)

Zhong, Z. W.; Ma, Z. X.; Jayawijayaningtiyas; Ngoh, J. H. H.

2016-10-01

With the emergence of unmanned aerial vehicles (UAVs) in multiple tactical defence missions, there was a need for an efficient visual signature suppression system for a more efficient stealth operation. One of our studies experimentally investigated the visual signature reduction of UAVs achieved through an active camouflage system. A prototype was constructed with newly developed operating software, Cloak, to provide active camouflage to the UAV model. The reduction of visual signature was analysed. Tests of the devices mounted on UAVs were conducted in another study. A series of experiments involved testing of the concept as well as the prototype. The experiments were conducted both in the laboratory and under normal environmental conditions. Results showed certain degrees of blending with the sky to create a camouflage effect. A mini-UAV made mostly out of transparent plastic was also designed and fabricated. Because of the transparency of the plastic material, the visibility of this UAV in the air is very small, and therefore the UAV is difficult to be detected. After re-designs and tests, eventually a practical system to reduce the visibility of UAVs viewed by human observers from the ground was developed. The system was evaluated during various outdoor tests. The scene target-to-background lightness contrast and the scene target-to-background colour contrast of the adaptive control system prototype were smaller than 10% at a stand-off viewing distance of 20-50 m.

Risk factors of overweight and obesity among preschool children with different ethnic background.

PubMed

Toselli, Stefania; Zaccagni, Luciana; Celenza, Francesca; Albertini, Augusta; Gualdi-Russo, Emanuela

2015-08-01

In this study, we evaluated the risk factors associated with overweight and obesity in 2,640 preschool children in Italy taking into account the ethnic background of the parents. Height and weight were measured and BMI was calculated. Personal and lifestyle data for the children (birth weight, type of breastfeeding, sleep duration, skipping breakfast, snacking, physical activity) and parents (ethnicity, educational level, occupation, weight, height) were collected by means of a questionnaire. Italian and Other European children generally showed the highest percentage of normal weight, while the other ethnic groups presented a greater imbalance. Overweight and obesity were high in African males, who also presented high birth weight. Breastfeeding was most common, although formula feeding was significantly higher in Italians than in immigrants. Immigrants, particularly males, tended to skip breakfast more than Italians. Physical activity was significantly higher in Italians than in immigrants. In the parents, underweight was particularly high in Italian and Other mothers. African parents had high rates of overweight and obesity and a low educational level. The most common profession was worker for the fathers and housewife for the mothers, with the exception of Italians in which clerical work prevailed. Multiple linear regression analysis showed that the BMI of children was closely related to the BMI of the parents and the birth weight. Hence, these are the most informative parameters in preventing obesity.

Active and long-lived permanent forearc deformation driven by the subduction seismic cycle

NASA Astrophysics Data System (ADS)

Aron Melo, Felipe Alejandro

I have used geological, geophysical and engineering methods to explore mechanisms of upper plate, brittle deformation at active forearc regions. My dissertation particularly addresses the permanent deformation style experienced by the forearc following great subduction ruptures, such as the 2010 M w8.8 Maule, Chile and 2011 Mw9.0 Tohoku, Japan earthquakes. These events triggered large, shallow seismicity on upper plate normal faults above the rupture reaching Mw7.0. First I present new structural data from the Chilean Coastal Cordillera over the rupture zone of the Maule earthquake. The study area contains the Pichilemu normal fault, which produced the large crustal aftershocks of the megathrust event. Normal faults are the major neotectonic structural elements but reverse faults also exist. Crustal seismicity and GPS surface displacements show that the forearc experiences pulses of rapid coseismic extension, parallel to the heave of the megathrust, and slow interseismic, convergence-parallel shortening. These cycles, over geologic time, build the forearc structural grain, reactivating structures properly-oriented respect to the deformation field of each stage of the interplate cycle. Great subduction events may play a fundamental role in constructing the crustal architecture of extensional forearc regions. Static mechanical models of coseismic and interseismic upper plate deformation are used to explore for distinct features that could result from brittle fracturing over the two stages of the interplate cycle. I show that the semi-elliptical outline of the first-order normal faults along the Coastal Cordillera may define the location of a characteristic, long-lived megathrust segment. Finally, using data from the Global CMT catalog I analyzed the seismic behavior through time of forearc regions that have experienced great subduction ruptures >Mw7.7 worldwide. Between 61% and 83% of the cases where upper plate earthquakes exhibited periods of increased seismicity above background levels occurred contemporaneous to megathrust ruptures. That correlation is stronger for normal fault events than reverse or strike-slip crustal earthquakes. More importantly, for any given megathrust the summation of the Mw accounted by the forearc normal fault aftershocks appears to have a positive linear correlation with the Mw of the subduction earthquake -- the larger the megathrust the larger the energy released by forearc events.

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

PubMed Central

Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM

2011-01-01

BACKGROUND AND PURPOSE Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACH Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. KEY RESULTS Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND IMPLICATIONS Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. PMID:21182490

The effects of Momordica charantia on obesity and lipid profiles of mice fed a high-fat diet

PubMed Central

Wang, Jun

2015-01-01

BACKGROUND/OBJECTIVES The present study was conducted to investigate the effects of dried Momordica charantia aqueous extracts (MCA) and ethanol extracts (MCE) on obesity and lipid profiles in mice fed a high-fat diet. MATERIALS/METHODS Forty two ICR mice were randomly divided into six groups. The normal group was fed a basal diet, and other groups were fed a 45% high-fat diet (HFD) for 7 weeks. The normal and HFD groups were also orally administered distilled water each day for 7 weeks. The remaining groups received Momordica charantia extract (0.5 or 1.0 g/kg/day MCA, and 0.5 or 1.0 g/kg/day MCE). In order to measure the anti-obesity and lipid profile improvement effects, body and visceral tissue weight, lipid profiles, plasma insulin levels, hepatic malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured. RESULTS Both MCA and MCE significantly decreased body and visceral tissue weight relative to those of the HFD group (P < 0.05). Additionally high doses of MCE and MCA significantly reduced the plasmatic insulin levels compared to the HFD groups (P < 0.05) to concentrations comparable to those found in the normal group. MCA and MCE supplementation also significantly modulated the lipid profiles in plasma, liver, and feces compared to mice fed the HFD (P < 0.05). Furthermore MCA and MCE significantly increased hepatic SOD activity, and reduced MDA generation in the liver of the HFD mice (P < 0.05). CONCLUSIONS Results from the present study suggest that Momordica charantia extracts have anti-obesity effects and the ability to modulate lipid prolife of mice fed a HFD by suppressing body weight gain, visceral tissue weight, plasma and hepatic lipid concentrations, and lipid peroxidation along with increasing lipid metabolism. PMID:26425278

Biased exonization of transposed elements in duplicated genes: A lesson from the TIF-IA gene

PubMed Central

Amit, Maayan; Sela, Noa; Keren, Hadas; Melamed, Ze'ev; Muler, Inna; Shomron, Noam; Izraeli, Shai; Ast, Gil

2007-01-01

Background Gene duplication and exonization of intronic transposed elements are two mechanisms that enhance genomic diversity. We examined whether there is less selection against exonization of transposed elements in duplicated genes than in single-copy genes. Results Genome-wide analysis of exonization of transposed elements revealed a higher rate of exonization within duplicated genes relative to single-copy genes. The gene for TIF-IA, an RNA polymerase I transcription initiation factor, underwent a humanoid-specific triplication, all three copies of the gene are active transcriptionally, although only one copy retains the ability to generate the TIF-IA protein. Prior to TIF-IA triplication, an Alu element was inserted into the first intron. In one of the non-protein coding copies, this Alu is exonized. We identified a single point mutation leading to exonization in one of the gene duplicates. When this mutation was introduced into the TIF-IA coding copy, exonization was activated and the level of the protein-coding mRNA was reduced substantially. A very low level of exonization was detected in normal human cells. However, this exonization was abundant in most leukemia cell lines evaluated, although the genomic sequence is unchanged in these cancerous cells compared to normal cells. Conclusion The definition of the Alu element within the TIF-IA gene as an exon is restricted to certain types of cancers; the element is not exonized in normal human cells. These results further our understanding of the delicate interplay between gene duplication and alternative splicing and of the molecular evolutionary mechanisms leading to genetic innovations. This implies the existence of purifying selection against exonization in single copy genes, with duplicate genes free from such constrains. PMID:18047649

Cells from the skin of patients with systemic sclerosis secrete chitinase 3-like protein 1

PubMed Central

Ho, Yuen Yee; Baron, Murray; Recklies, Anneliese D.; Roughley, Peter J.; Mort, John S.

2014-01-01

Background The chitinase-like protein, Chi3L1, is associated with increased fibrotic activity as well as inflammatory processes. The capacity of skin cells from systemic sclerosis (SSc) patients to produce Chi3L1, and the stimulation of its synthesis by cytokines or growth factors known to be associated with SSc, was investigated. Methods Cells were isolated from forearm and/or abdomen skin biopsies taken from SSc patients and normal individuals and stimulated with cytokines and growth factors to assess Chi3L1 expression. Chi3L1-expressing cells were characterized by immunohistochemical staining. Results Chi3L1 was not secreted by skin cells from normal individuals nor was its synthesis induced by any of the cytokines or growth factors investigated. In contrast, Chi3L1 secretion was induced by OSM or IL-1 in cells from all forearm biopsies of SSc patients, and endogenous secretion in the absence of cytokines was detected in several specimens. Patients with Chi3L1-producing cells at both the arm and abdomen had a disease duration of less than 3 years. Endogenous Chi3L1 production was not a property of the major fibroblast population nor of myofibroblasts, but rather was related to the presence of stem-like cells not present in normal skin. Other cells, however, contributed to the upregulation of Chi3L1 by OSM. Conclusions The emergence of cells primed to respond to OSM with increased Chi3L1 production appears to be associated with pathological processes active in SSc. General significance The presence of progenitor cells expressing the chilectin Chi3L1 in SSc skin appears to play a role in the initiation of the disease process. PMID:26675476

Dynamic Three-Dimensional Shoulder Mri during Active Motion for Investigation of Rotator Cuff Diseases

PubMed Central

Tempelaere, Christine; Pierrart, Jérome; Lefèvre-Colau, Marie-Martine; Vuillemin, Valérie; Cuénod, Charles-André; Hansen, Ulrich; Mir, Olivier; Skalli, Wafa; Gregory, Thomas

2016-01-01

Background MRI is the standard methodology in diagnosis of rotator cuff diseases. However, many patients continue to have pain despite treatment, and MRI of a static unloaded shoulder seems insufficient for best diagnosis and treatment. This study evaluated if Dynamic MRI provides novel kinematic data that can be used to improve the understanding, diagnosis and best treatment of rotator cuff diseases. Methods Dynamic MRI provided real-time 3D image series and was used to measure changes in the width of subacromial space, superior-inferior translation and anterior-posterior translation of the humeral head relative to the glenoid during active abduction. These measures were investigated for consistency with the rotator cuff diseases classifications from standard MRI. Results The study included: 4 shoulders with massive rotator cuff tears, 5 shoulders with an isolated full-thickness supraspinatus tear, 5 shoulders with tendinopathy and 6 normal shoulders. A change in the width of subacromial space greater than 4mm differentiated between rotator cuff diseases with tendon tears (massive cuff tears and supraspinatus tear) and without tears (tendinopathy) (p = 0.012). The range of the superior-inferior translation was higher in the massive cuff tears group (6.4mm) than in normals (3.4mm) (p = 0.02). The range of the anterior-posterior translation was higher in the massive cuff tears (9.2 mm) and supraspinatus tear (9.3 mm) shoulders compared to normals (3.5mm) and tendinopathy (4.8mm) shoulders (p = 0.05). Conclusion The Dynamic MRI enabled a novel measure; ‘Looseness’, i.e. the translation of the humeral head on the glenoid during an abduction cycle. Looseness was better able at differentiating different forms of rotator cuff disease than a simple static measure of relative glenohumeral position. PMID:27434235

A quantitative systems pharmacology model of blood coagulation network describes in vivo biomarker changes in non-bleeding subjects.

PubMed

Lee, D; Nayak, S; Martin, S W; Heatherington, A C; Vicini, P; Hua, F

2016-12-01

Essentials Baseline coagulation activity can be detected in non-bleeding state by in vivo biomarker levels. A detailed mathematical model of coagulation was developed to describe the non-bleeding state. Optimized model described in vivo biomarkers with recombinant activated factor VII treatment. Sensitivity analysis predicted prothrombin fragment 1 + 2 and D-dimer are regulated differently. Background Prothrombin fragment 1 + 2 (F 1 + 2 ), thrombin-antithrombin III complex (TAT) and D-dimer can be detected in plasma from non-bleeding hemostatically normal subjects or hemophilic patients. They are often used as safety or pharmacodynamic biomarkers for hemostatis-modulating therapies in the clinic, and provide insights into in vivo coagulation activity. Objectives To develop a quantitative systems pharmacology (QSP) model of the blood coagulation network to describe in vivo biomarkers, including F 1 + 2 , TAT, and D-dimer, under non-bleeding conditions. Methods The QSP model included intrinsic and extrinsic coagulation pathways, platelet activation state-dependent kinetics, and a two-compartment pharmacokinetics model for recombinant activated factor VII (rFVIIa). Literature data on F 1 + 2 and D-dimer at baseline and changes with rFVIIa treatment were used for parameter optimization. Multiparametric sensitivity analysis (MPSA) was used to understand key proteins that regulate F 1 + 2 , TAT and D-dimer levels. Results The model was able to describe tissue factor (TF)-dependent baseline levels of F 1 + 2 , TAT and D-dimer in a non-bleeding state, and their increases in hemostatically normal subjects and hemophilic patients treated with different doses of rFVIIa. The amount of TF required is predicted to be very low in a non-bleeding state. The model also predicts that these biomarker levels will be similar in hemostatically normal subjects and hemophilic patients. MPSA revealed that F 1 + 2 and TAT levels are highly correlated, and that D-dimer is more sensitive to the perturbation of coagulation protein concentrations. Conclusions A QSP model for non-bleeding baseline coagulation activity was established with data from clinically relevant in vivo biomarkers at baseline and changes in response to rFVIIa treatment. This model will provide future mechanistic insights into this system. © 2016 International Society on Thrombosis and Haemostasis.

Vitamin B5 and N-acetylcysteine in nonalcoholic steatohepatitis: a pre-clinical study in a dietary mouse model

PubMed Central

Machado, Mariana Verdelho; Kruger, Leandi; Jewell, Mark L.; Michelotti, Gregory Alexander; de Almeida Pereira, Thiago; Xie, Guanhua; Moylan, Cynthia A.; Diehl, Anna Mae

2015-01-01

Background Nonalcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease and second indication for liver transplantation in the Western world. Effective therapy is still not available. Previously we showed a critical role for caspase-2 in the pathogenesis of nonalcoholic steatohepatitis (NASH), the potentially progressive form of NAFLD. An imbalance between free Coenzyme A (CoA) and acyl-CoA ratio is known to induce caspase-2 activation. Objectives We aimed to evaluate CoA metabolism and the effects of supplementation with CoA precursors, pantothenate and cysteine, in mouse models of NASH. Methods CoA metabolism was evaluated in methionine-choline deficient (MCD) and Western diet mouse models of NASH. MCD-diet fed mice were treated with pantothenate and N-acetylcysteine or placebo to determine effects on NASH. Results Liver free CoA content was reduced, pantothenate kinase (PANK), the rate-limiting enzyme in the CoA biosynthesis pathway, was down-regulated, and CoA degrading enzymes were increased in mice with NASH. Decreased hepatic free CoA content was associated with increased caspase-2 activity, and correlated with worse liver cell apoptosis, inflammation and fibrosis. Treatment with pantothenate and N-acetylcysteine did not inhibit caspase-2 activation, improve NASH, normalize PANK expression, or restore free CoA levels in MCD diet-fed mice. Conclusion In mice with NASH, hepatic CoA metabolism is impaired, leading to decreased free CoA content, activation of caspase-2, and increased liver cell apoptosis. Dietary supplementation with CoA precursors did not restore CoA levels or improve NASH, suggesting that alternative approaches are necessary to normalize free CoA during NASH. PMID:26403427

Kinetic comparison of tissue non-specific and placental human alkaline phosphatases expressed in baculovirus infected cells: application to screening for Down's syndrome

PubMed Central

Denier, Colette C; Brisson-Lougarre, Andrée A; Biasini, Ghislaine G; Grozdea, Jean J; Fournier, Didier D

2002-01-01

Background In humans, there are four alkaline phosphatases, and each form exibits a characteristic pattern of tissue distribution. The availability of an easy method to reveal their activity has resulted in large amount of data reporting correlations between variations in activity and illnesses. For example, alkaline phosphatase from neutrophils of mothers pregnent with a trisomy 21 fetus (Down's syndrome) displays significant differences both in its biochemical and immunological properties, and in its affinity for some specific inhibitors. Results To analyse these differences, the biochemical characteristics of two isozymes (non specific and placental alkaline phosphatases) were expressed in baculovirus infected cells. Comparative analysis of the two proteins allowed us to estimate the kinetic constants of denaturation and sensitivity to two inhibitors (L-p-bromotetramisole and thiophosphate), allowing better discrimination between the two enzymes. These parameters were then used to estimate the ratio of the two isoenzymes in neutrophils of pregnant mothers with or without a trisomy 21 fetus. It appeared that the placental isozyme represented 13% of the total activity of neutrophils of non pregnant women. This proportion did not significantly increase with normal pregnancy. By contrast, in pregnancies with trisomy 21 fetus, the proportion reached 60–80% of activity. Conclusion Over-expression of the placental isozyme compared with the tissue-nonspecific form in neutrophils of mother with a trisomy 21 fetus may explain why the characteristics of the alkaline phosphatase in these cells is different from normal. Application of this knowledge could improve the potential of using alkaline phosphatase measurements to screen for Down's syndrome. PMID:11818032

Laparoscopic Total Extraperitoneal Hernia Repair Outcomes

PubMed Central

Bresnahan, Erin R.

2016-01-01

Background and Objectives: Laparoscopic inguinal hernia repair has become increasingly popular as an alternative to open surgery. The purpose of this study was to evaluate the safety and effectiveness of the laparoscopic total extraperitoneal procedure with the use of staple fixation and polypropylene mesh. Methods: A retrospective chart review examined outcomes of 1240 laparoscopic hernia operations in 783 patients, focusing on intraoperative and early postoperative complications, pain, and time until return to work and normal physical activities. Results: There were no intraoperative complications in this series; 106 patients experienced early postoperative complications across 8 evaluated categories: urinary retention (4.1%), seroma (3.0%), testicular/hemiscrotal swelling (1.9%), testicular atrophy (0%), hydrocele (0.6%), mesh infection (0.1%), and neurological symptoms (transient, 1.0%; persistent, 0.2%). Patients used an average of 5.6 Percocet pills after the procedure, and mean times until return to work and normal activities, including their routine exercise regimen, were 3.0 and 3.8 days, respectively. Conclusion: Complication rates and convalescence times were considered equivalent or superior to those found in other studies assessing both laparoscopic and open techniques. The usage of multiple Endostaples did not result in increased neurologic complications in the early postoperative period when compared with findings in the literature. In the hands of an experienced surgeon, total extraperitoneal repair is a safe, effective alternative to open inguinal hernia repair. PMID:27493471

Effect of Alpinia calcarata on glucose uptake in diabetic rats-an in vitro and in vivo model

PubMed Central

2014-01-01

Background Diabetes mellitus is a heterogeneous metabolic disorders characterized by abnormally high levels of blood glucose The main objective of the present work is to study the effect of Alpinia calcarata on glucose uptake in streptozotocin (STZ) induced diabetic rats. Methods The diabetes was induced by single dose of STZ (45 mg/kg) in citrate buffer, while the normal control group was given the vehicle (citrate buffer) only. After induction of diabetes, the diabetic animals were treated with ethanolic extract of Alpinia calcarata (200 mg/kg) and glibenclamide (2 mg/kg) for 30 days. Blood glucose estimation was performed every week of the study. At the end of study period, animals were sacrificed for biochemical studies. Results Streptozotocin induced diabetic rats shows the altered levels of various biochemical profiles. Those levels were brought back to near normal upon treatment with ethanolic extract of Alpinia calcarata and standard drug glibanclamide. No significant changes were observed on treatment with plant extract alone group indicated that there are no toxic substances present in Alpinia calcarata. The antidiabetic activity of plant extract was also further confirmed by histopathological studies. The ethanolic extract of Alpinia calcarata shows significant inhibition of alpha glucosidase activity and also enhancing the glucose uptake in rat hemidiaphragm. Conclusions In conclusion, the ethanolic extract of Alpinia calcarata ameliorates the condition associated with diabetes. PMID:24502532

Three-dimensional facial recognition using passive long-wavelength infrared polarimetric imaging.

PubMed

Yuffa, Alex J; Gurton, Kristan P; Videen, Gorden

2014-12-20

We use a polarimetric camera to record the Stokes parameters and the degree of linear polarization of long-wavelength infrared radiation emitted by human faces. These Stokes images are combined with Fresnel relations to extract the surface normal at each pixel. Integrating over these surface normals yields a three-dimensional facial image. One major difficulty of this technique is that the normal vectors determined from the polarizations are not unique. We overcome this problem by introducing an additional boundary condition on the subject. The major sources of error in producing inversions are noise in the images caused by scattering of the background signal and the ambiguity in determining the surface normals from the Fresnel coefficients.

Quasi-normal modes from non-commutative matrix dynamics

NASA Astrophysics Data System (ADS)

Aprile, Francesco; Sanfilippo, Francesco

2017-09-01

We explore similarities between the process of relaxation in the BMN matrix model and the physics of black holes in AdS/CFT. Focusing on Dyson-fluid solutions of the matrix model, we perform numerical simulations of the real time dynamics of the system. By quenching the equilibrium distribution we study quasi-normal oscillations of scalar single trace observables, we isolate the lowest quasi-normal mode, and we determine its frequencies as function of the energy. Considering the BMN matrix model as a truncation of N=4 SYM, we also compute the frequencies of the quasi-normal modes of the dual scalar fields in the AdS5-Schwarzschild background. We compare the results, and we finda surprising similarity.

Speech Processing to Improve the Perception of Speech in Background Noise for Children With Auditory Processing Disorder and Typically Developing Peers.

PubMed

Flanagan, Sheila; Zorilă, Tudor-Cătălin; Stylianou, Yannis; Moore, Brian C J

2018-01-01

Auditory processing disorder (APD) may be diagnosed when a child has listening difficulties but has normal audiometric thresholds. For adults with normal hearing and with mild-to-moderate hearing impairment, an algorithm called spectral shaping with dynamic range compression (SSDRC) has been shown to increase the intelligibility of speech when background noise is added after the processing. Here, we assessed the effect of such processing using 8 children with APD and 10 age-matched control children. The loudness of the processed and unprocessed sentences was matched using a loudness model. The task was to repeat back sentences produced by a female speaker when presented with either speech-shaped noise (SSN) or a male competing speaker (CS) at two signal-to-background ratios (SBRs). Speech identification was significantly better with SSDRC processing than without, for both groups. The benefit of SSDRC processing was greater for the SSN than for the CS background. For the SSN, scores were similar for the two groups at both SBRs. For the CS, the APD group performed significantly more poorly than the control group. The overall improvement produced by SSDRC processing could be useful for enhancing communication in a classroom where the teacher's voice is broadcast using a wireless system.

The use of the picture–word interference paradigm to examine naming abilities in aphasic individuals

PubMed Central

Hashimoto, Naomi; Thompson, Cynthia K.

2015-01-01

Background Although naming deficits are well documented in aphasia, on-line measures of naming processes have been little investigated. The use of on-line measures may offer further insight into the nature of aphasic naming deficits that would otherwise be difficult to interpret when using off-line measures. Aims The temporal activation of semantic and phonological processes was tracked in older normal control and aphasic individuals using a picture–word interference paradigm. The purpose of the study was to examine how word interference results can augment and/or corroborate standard language testing in the aphasic group, as well as to examine temporal patterns of activation in the aphasic group when compared to a normal control group. Methods & Procedures A total of 20 older normal individuals and 11 aphasic individuals participated. Detailed measures of each aphasic individual's language and naming skills were obtained. A visual picture–word interference paradigm was used in which the words bore either a semantic, phonological, or no relationship to 25 pictures. These competitor words were presented at stimulus onset asynchronies of −300 ms, +300 ms, and 0 ms. Outcomes & Results Analyses of naming RTs in both groups revealed significant early semantic interference effects, mid-semantic interference effects, and mid-phonological facilitation effects. A matched control-aphasic group comparison revealed no differences in the temporal activation of effects during the course of naming. Partial support for this RT pattern was found in the aphasic naming error pattern. The aphasic group also demonstrated greater SIEs and PFEs compared to the matched control group, which indicated disruptions of the phonological processing stage. Analyses of behavioural performances of the aphasic group corroborated this finding. Conclusions The aphasic naming RTs results were unexpected given the results from the priming literature, which has supported the idea of slowed or reduced patterns of activation in aphasic individuals. However, analyses of naming RTs also confirmed the behavioural finding of a disruption surrounding phonological processes; thus, the analyses of naming latencies offers another potential means of pinpointing breakdowns of lexical access in individuals with aphasia. PMID:26166927

Assessment of Point-of-Care Diagnostics for G6PD Deficiency in Malaria Endemic Rural Eastern Indonesia

PubMed Central

Satyagraha, Ari W.; Sadhewa, Arkasha; Elvira, Rosalie; Elyazar, Iqbal; Feriandika, Denny; Antonjaya, Ungke; Oyong, Damian; Subekti, Decy; Rozi, Ismail E.; Domingo, Gonzalo J.; Harahap, Alida R.; Baird, J. Kevin

2016-01-01

Background Patients infected by Plasmodium vivax or Plasmodium ovale suffer repeated clinical attacks without primaquine therapy against latent stages in liver. Primaquine causes seriously threatening acute hemolytic anemia in patients having inherited glucose-6-phosphate dehydrogenase (G6PD) deficiency. Access to safe primaquine therapy hinges upon the ability to confirm G6PD normal status. CareStart G6PD, a qualitative G6PD rapid diagnostic test (G6PD RDT) intended for use at point-of-care in impoverished rural settings where most malaria patients live, was evaluated. Methodology/Principal Findings This device and the standard qualitative fluorescent spot test (FST) were each compared against the quantitative spectrophotometric assay for G6PD activity as the diagnostic gold standard. The assessment occurred at meso-endemic Panenggo Ede in western Sumba Island in eastern Indonesia, where 610 residents provided venous blood. The G6PD RDT and FST qualitative assessments were performed in the field, whereas the quantitative assay was performed in a research laboratory at Jakarta. The median G6PD activity ≥5 U/gHb was 9.7 U/gHb and was considered 100% of normal activity. The prevalence of G6PD deficiency by quantitative assessment (<5 U/gHb) was 7.2%. Applying 30% of normal G6PD activity as the cut-off for qualitative testing, the sensitivity, specificity, positive predictive value, and negative predictive value for G6PD RDT versus FST among males were as follows: 100%, 98.7%, 89%, and 100% versus 91.7%, 92%, 55%, and 99%; P = 0.49, 0.001, 0.004, and 0.24, respectively. These values among females were: 83%, 92.7%, 17%, and 99.7% versus 100%, 92%, 18%, and 100%; P = 1.0, 0.89, 1.0 and 1.0, respectively. Conclusions/Significance The overall performance of G6PD RDT, especially 100% negative predictive value, demonstrates suitable safety for G6PD screening prior to administering hemolytic drugs like primaquine and many others. Relatively poor diagnostic performance among females due to mosaic G6PD phenotype is an inherent limitation of any current practical screening methodology. PMID:26894297

Frequency-Shift Hearing Aid

NASA Technical Reports Server (NTRS)

Weinstein, Leonard M.

1994-01-01

Proposed hearing aid maps spectrum of speech into band of lower frequencies at which ear remains sensitive. By redirecting normal speech frequencies into frequency band from 100 to 1,500 Hz, hearing aid allows people to understand normal conversation, including telephone calls. Principle operation of hearing aid adapted to other uses such as, clearing up noisy telephone or radio communication. In addition, loud-speakers more easily understood in presence of high background noise.

Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

NASA Astrophysics Data System (ADS)

Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

2015-11-01

Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

Molecular Targeting of Prostate Cancer During Androgen Ablation: Inhibition of CHES1/FOXN3

DTIC Science & Technology

2011-05-01

activity (Firefly luciferase) was normalized to Renilla luciferase activity. Results are presented as fold-change in PSA reporter activity...reporter (DLR) assays performed. In each sample, the CHES1-RR1/3.5 reporter activity (Firefly luciferase) was normalized to Renilla luciferase...4.0) reporter activity (Firefly luciferase) was normalized to Renilla luciferase activity. Results are presented as fold-change in BNIP3 reporter

Distinct DNA methylation patterns associated with active and inactive centromeres of the maize B chromosome.

PubMed

Koo, Dal-Hoe; Han, Fangpu; Birchler, James A; Jiang, Jiming

2011-06-01

Centromeres are determined by poorly understood epigenetic mechanisms. Centromeres can be activated or inactivated without changing the underlying DNA sequences. However, virtually nothing is known about the epigenetic transition of a centromere from an active to an inactive state because of the lack of examples of the same centromere exhibiting alternative forms and being distinguishable from other centromeres. The centromere of the supernumerary B chromosome of maize provides such an opportunity because its functional core can be cytologically tracked, and an inactive version of the centromere is available. We developed a DNA fiber-based technique that can be used to assess the levels of cytosine methylation associated with repetitive DNA sequences. We report that DNA sequences in the normal B centromere exhibit hypomethylation. This methylation pattern is not affected by the genetic background or structural rearrangement of the B chromosome, but is slightly changed when the B chromosome is transferred to oat as an addition chromosome. In contrast, an inactive version of this same centromere exhibits hypermethylation, indicating that the inactive centromere was modified into a different epigenetic state at the DNA level.

Premiers résultats du réseau sismique (CRLN) de la partie ouest du rift de Corinthe : évidence de la réactivation d'une ancienne faille

NASA Astrophysics Data System (ADS)

Lyon-Caen, Hélène; Papadimitriou, Panayotis; Deschamps, Anne; Bernard, Pascal; Makropoulos, Kostas; Pacchiani, Francesco; Patau, Geneviève

2004-03-01

The 12 stations Corinth Rift Laboratory Seismological Network (CRLNET) aims at monitoring the seismicity ( Ml>1) in the CRL area and at constraining the geometry of active structures at depth. Two years of microseismicity (2000-2001) recorded by the CRLNET in the Aigion area shows: (1) background seismicity inside the Corinth rift at depth of 4.5-11 km, deepening towards the north and no activity in the upper 4 km of the crust - this seismicity is not clearly related to major faults observed at the surface -; (2) a swarm, 6 km south of the city of Aigion, associated with the Mw=4.2, 8 April 2001 earthquake. This earthquake occurred at 6 km depth, on a SW-NE oriented fault dipping 40° to the northwest and corresponds to normal faulting with a right lateral component of slip. It likely occurred on an old structure reactivated in the present stress field. To cite this article: H. Lyon-Caen et al., C. R. Geoscience 336 (2004).

Radiation sensors for medical, industrial and environmental applications: how to engage with schools and the general public

NASA Astrophysics Data System (ADS)

Seitz, B.; Campos Rivera, N.; Gray, R.; Powell, A.; Thomson, F.

2018-01-01

Radiation, radiation detection and radiation protection are topics in physics and its applications which generate a wide interest in the public. This interest is either generated through medical procedures, applications of nuclear energy or nuclear accidents. The technical nature of these topics usually means that they are not well covered in the normal education stream, opening many opportunities to engage with schools and the general public to showcase the latest developments and their applications. The detection of radiation is at the very heart of understanding radiation, its fascination and associated fears. The outreach group of the nuclear physics group at the University of Glasgow demonstrates a number of successful outreach activities centred around radiation detection and described in this paper, focusing on activities delivered to a variety of audiences and related to applied nuclear physics work within our group. These concentrate on the application of novel sensor technologies for nuclear decommissioning, medical imaging modalities and the monitoring of environmental radioactivity. The paper will provide some necessary background material as well as practical instructions for some of the activities developed.

A broad survey reveals substitution tolerance of residues ligating FeS clusters in [NiFe] hydrogenase

PubMed Central

2014-01-01

Background In order to understand the effects of FeS cluster attachment in [NiFe] hydrogenase, we undertook a study to substitute all 12 amino acid positions normally ligating the three FeS clusters in the hydrogenase small subunit. Using the hydrogenase from Alteromonas macleodii “deep ecotype” as a model, we substituted one of four amino acids (Asp, His, Asn, Gln) at each of the 12 ligating positions because these amino acids are alternative coordinating residues in otherwise conserved-cysteine positions found in a broad survey of NiFe hydrogenase sequences. We also hoped to discover an enzyme with elevated hydrogen evolution activity relative to a previously reported “G1” (H230C/P285C) improved enzyme in which the medial FeS cluster Pro and the distal FeS cluster His were each substituted for Cys. Results Among all the substitutions screened, aspartic acid substitutions were generally well-tolerated, and examination suggests that the observed deficiency in enzyme activity may be largely due to misprocessing of the small subunit of the enzyme. Alignment of hydrogenase sequences from sequence databases revealed many rare substitutions; the five substitutions present in databases that we tested all exhibited measurable hydrogen evolution activity. Select substitutions were purified and tested, supporting the results of the screening assay. Analysis of these results confirms the importance of small subunit processing. Normalizing activity to quantity of mature small subunit, indicative of total enzyme maturation, weakly suggests an improvement over the “G1” enzyme. Conclusions We have comprehensively screened 48 amino acid substitutions of the hydrogenase from A. macleodii “deep ecotype”, to understand non-canonical ligations of amino acids to FeS clusters and to improve hydrogen evolution activity of this class of hydrogenase. Our studies show that non-canonical ligations can be functional and also suggests a new limiting factor in the production of active enzyme. PMID:24934472

Retinoic Acid 4-Hydroxylase Inducibility and Clinical Response to Isotretinoin in Acne Patients

PubMed Central

Wang, Frank; Kwak, Heh Shin R.; Elbuluk, Nada; Kaczmarek, Anya L.; Hamilton, Ted; Voorhees, John J.; Fisher, Gary J.; Kang, Sewon

2011-01-01

Background The cytochrome P450 enzyme CYP26 (retinoic acid 4-hydroxylase) initiates the catabolism of all-trans retinoic acid (tRA) and limits the effects of tRA. The CYP26 enzyme acts on tRA, but not 13-cis RA (isotretinoin), a retinoid used to treat severe acne. However, 13-cis RA can isomerize to tRA, which can then be metabolized by CYP26. Objective In healthy subjects, we assessed the variability of CYP26 enzymatic activity. We then investigated whether response to oral 13-cis RA among acne patients correlates with variability in CYP26 expression. Methods In healthy subjects, we isolated microsomal fractions from the epidermis of keratome biopsies and measured CYP26 enzymatic activity in untreated skin and skin treated with tRA. Enzymatic activity was determined based on rate of formation of 4-hydroxy RA (pg/min) per mg microsomal protein. Using real-time PCR we quantified CYP26 mRNA induction after tRA application in acne patients who responded or did not respond to one course of 13-cis RA. Results In normal skin (N=118), CYP26 enzymatic activity was widely variable (1–180 pg/min per mg microsomal fraction; mean 42.7 ± 3.5). Furthermore, CYP26 enzymatic activity was inducible in a dose-dependent manner in normal skin following tRA application, but not correlated with age or sex (N=29). In acne patients, CYP26 mRNA induction following 0.1% tRA application did not differ (P>0.05) between subjects who responded (N=8, 587±325 fold) or did not respond (N=8, 657±227 fold) to one course of 13-cis RA. Limitations The small number of acne patients treated with 13-cis RA was a major limitation. Conclusion Factors other than CYP26 activity may determine response to isotretinoin in acne. PMID:19525031

(14)C levels in the vicinity of the Fukushima Dai-ichi Nuclear Power Plant prior to the 2011 accident.

PubMed

Xu, Sheng; Cook, Gordon T; Cresswell, Alan J; Dunbar, Elaine; Freeman, Stewart P H T; Hastie, Helen; Hou, Xiaolin; Jacobsson, Piotr; Naysmith, Philip; Sanderson, David C W; Tripney, Brian G; Yamaguchi, Katsuhiko

2016-06-01

A 50-year-old Japanese cedar (Cryptomeria japonica) from Okuma, ∼1 km southwest of the Fukushima Dai-ichi Nuclear Power Plant, was cored and each annual ring was analysed for (14)C. The (14)C specific activity values varied from 330.4 Bq kg(-1) C in the tree ring formed in 1971 to 231.2 Bq kg(-1) C in the 2014 ring. During the periods 1971-1976 and 2011-2014, the (14)C specific activities are indistinguishable from the ambient background values. However, compared with the ambient atmospheric levels, the (14)C specific activities between 1977 and 2010 are significantly elevated, clearly indicating (14)C discharges from the reactors during their normal operations. In addition, the specific activities are positively correlated with the annual electricity generation values. The excess (14)C specific activities were <36 Bq kg(-1) C, corresponding to an additional annual effective dose of <2 μSv via the food ingestion pathway in the study location. The primary wind direction is east-southeast/southeast with a frequency of ∼30%, in comparison to ∼20% frequency for the direction of the site under study (north-northeast/northeast). This would tend to indicate a similar magnitude of additional effective dose and consequently no significant radiological impact of atmospheric (14)C discharges from the FDNPP during the entire period of normal operations. Additionally, no (14)C pulse in activity can be observed in the year 2011 ring. This might be caused by a limited (14)C release from the damaged reactors during the accident or that the prevailing wind during the short period of release (11th-25th March 2011) was not in the direction of Okuma. Copyright © 2016 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, Nancy L., E-mail: nlcho@partners.org; Lin, Chi-Iou; Du, Jinyan

Highlights: Black-Right-Pointing-Pointer Kinome profiling is a novel technique for identifying activated kinases in human cancers. Black-Right-Pointing-Pointer Src activity is increased in invasive thyroid cancers. Black-Right-Pointing-Pointer Inhibition of Src activity decreased proliferation and invasion in vitro. Black-Right-Pointing-Pointer Further investigation of Src targeted therapies in thyroid cancer is warranted. -- Abstract: Background: Novel therapies are needed for the treatment of invasive thyroid cancers. Aberrant activation of tyrosine kinases plays an important role in thyroid oncogenesis. Because current targeted therapies are biased toward a small subset of tyrosine kinases, we conducted a study to reveal novel therapeutic targets for thyroid cancer using amore » bead-based, high-throughput system. Methods: Thyroid tumors and matched normal tissues were harvested from twenty-six patients in the operating room. Protein lysates were analyzed using the Luminex immunosandwich, a bead-based kinase phosphorylation assay. Data was analyzed using GenePattern 3.0 software and clustered according to histology, demographic factors, and tumor status regarding capsular invasion, size, lymphovascular invasion, and extrathyroidal extension. Survival and invasion assays were performed to determine the effect of Src inhibition in papillary thyroid cancer (PTC) cells. Results: Tyrosine kinome profiling demonstrated upregulation of nine tyrosine kinases in tumors relative to matched normal thyroid tissue: EGFR, PTK6, BTK, HCK, ABL1, TNK1, GRB2, ERK, and SRC. Supervised clustering of well-differentiated tumors by histology, gender, age, or size did not reveal significant differences in tyrosine kinase activity. However, supervised clustering by the presence of invasive disease showed increased Src activity in invasive tumors relative to non-invasive tumors (60% v. 0%, p < 0.05). In vitro, we found that Src inhibition in PTC cells decreased cell invasion and proliferation. Conclusion: Global kinome analysis enables the discovery of novel targets for thyroid cancer therapy. Further investigation of Src targeted therapy for advanced thyroid cancer is warranted.« less

An investigation into the enzyme histochemistry of adenocarcinomas of human large intestine and of the transitional epithelium immediately adjacent to them

PubMed Central

Marsden, J. R.; Dawson, I. M. P.

1974-01-01

Histochemical enzymatic studies were performed on 30 freshly resected large bowel carcinomas, 30 samples of normal colonic epithelium, and six samples of the histologically normal epithelium (so-called transitional epithelium) immediately adjacent to a carcinoma. Five enzymes were studied: nicotine adenine dinucleotide tetrazolium reductase (NADH-TR), glucose-6-phosphate dehydrogenase, succinate dehydrogenase, monoamine oxidase, and acid phosphatase. Quantitative and qualitative differences in enzyme activity were observed between normal, transitional, and carcinomatous mucosa as follows: monoamine oxidase activity was moderate in normal mucosa, high in transitional mucosa, and low in carcinoma. Succinate dehydrogenase activity was high in transitional mucosa and low or moderate in normal and carcinomatous mucosa. Glucose-6-phosphate dehydrogenase activity showed a gradation from low in normal mucosa to high in carcinoma while acid phosphatase showed the reverse of this pattern. The tetrazolium reductase activity was low or moderate in normal and transitional mucosa and high in carcinoma. These differences in enzyme activity and their possible clinical and metabolic significance are discussed. ImagesFig 2Fig 3 PMID:4154840

Temporal changes in stress preceding the 2004-2008 eruption of Mount St. Helens, Washington

USGS Publications Warehouse

Lehto, H.L.; Roman, D.C.; Moran, S.C.

2010-01-01

The 2004-2008 eruption of Mount St. Helens (MSH), Washington, was preceded by a swarm of shallow volcano-tectonic earthquakes (VTs) that began on September 23, 2004. We calculated locations and fault-plane solutions (FPS) for shallow VTs recorded during a background period (January 1999 to July 2004) and during the early vent-clearing phase (September 23 to 29, 2004) of the 2004-2008 eruption. FPS show normal and strike-slip faulting during the background period and on September 23; strike-slip and reverse faulting on September 24; and a mixture of strike-slip, reverse, and normal faulting on September 25-29. The orientation of ??1 beneath MSH, as estimated from stress tensor inversions, was found to be sub-horizontal for all periods and oriented NE-SW during the background period, NW-SE on September 24, and NE-SW on September 25-29. We suggest that the ephemeral ~90?? change in ??1 orientation was due to intrusion and inflation of a NE-SW-oriented dike in the shallow crust prior to the eruption onset. ?? 2010 Elsevier B.V.

SHAPE Selection (SHAPES) enrich for RNA structure signal in SHAPE sequencing-based probing data

PubMed Central

Poulsen, Line Dahl; Kielpinski, Lukasz Jan; Salama, Sofie R.; Krogh, Anders; Vinther, Jeppe

2015-01-01

Selective 2′ Hydroxyl Acylation analyzed by Primer Extension (SHAPE) is an accurate method for probing of RNA secondary structure. In existing SHAPE methods, the SHAPE probing signal is normalized to a no-reagent control to correct for the background caused by premature termination of the reverse transcriptase. Here, we introduce a SHAPE Selection (SHAPES) reagent, N-propanone isatoic anhydride (NPIA), which retains the ability of SHAPE reagents to accurately probe RNA structure, but also allows covalent coupling between the SHAPES reagent and a biotin molecule. We demonstrate that SHAPES-based selection of cDNA–RNA hybrids on streptavidin beads effectively removes the large majority of background signal present in SHAPE probing data and that sequencing-based SHAPES data contain the same amount of RNA structure data as regular sequencing-based SHAPE data obtained through normalization to a no-reagent control. Moreover, the selection efficiently enriches for probed RNAs, suggesting that the SHAPES strategy will be useful for applications with high-background and low-probing signal such as in vivo RNA structure probing. PMID:25805860

Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder

PubMed Central

Voon, V; Brezing, C; Gallea, C; Hallett, M

2014-01-01

Background Conversion disorder is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that conversion disorder with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amgydala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Methods Subjects performed either an internally or externally generated two-button action selection task in a functional MRI study. Results Eleven conversion disorder patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. Conclusion We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system which is both hypoactive and functionally disconnected from prefrontal top-down regulation. PMID:21935985

The role of platelet and endothelial GARP in thrombosis and hemostasis

PubMed Central

Vermeersch, Elien; Denorme, Frederik; Maes, Wim; De Meyer, Simon F.; Vanhoorelbeke, Karen; Edwards, Justin; Shevach, Ethan M.; Unutmaz, Derya; Fujii, Hodaka; Deckmyn, Hans; Tersteeg, Claudia

2017-01-01

Background Glycoprotein-A Repetitions Predominant protein (GARP or LRRC32) is present on among others human platelets and endothelial cells. Evidence for its involvement in thrombus formation was suggested by full knockout of GARP in zebrafish. Objectives To evaluate the role of GARP in platelet physiology and in thrombus formation using platelet and endothelial conditional GARP knock out mice. Methods Platelet and endothelial specific GARP knockout mice were generated using the Cre-loxP recombination system. The function of platelets without GARP was measured by flow cytometry, spreading analysis and aggregometry using PAR4-activating peptide and collagen related peptide. Additionally, clot retraction and collagen-induced platelet adhesion and aggregation under flow were analyzed. Finally, in vivo tail bleeding time, occlusion time of the mesenteric and carotid artery after FeCl3-induced thrombosis were determined in platelet and endothelial specific GARP knock out mice. Results Platelet specific GARP knockout mice had normal surface GPIb, GPVI and integrin αIIb glycoprotein expression. Although GARP expression was increased upon platelet activation, platelets without GARP displayed normal agonist induced activation, spreading on fibrinogen and aggregation responses. Furthermore, absence of GARP on platelets did not influence clot retraction and had no impact on thrombus formation on collagen-coated surfaces under flow. In line with this, neither the tail bleeding time nor the occlusion time in the carotid- and mesenteric artery after FeCl3-induced thrombus formation in platelet or endothelial specific GARP knock out mice were affected. Conclusions Evidence is provided that platelet and endothelial GARP are not important in hemostasis and thrombosis in mice. PMID:28278197

Kinetics and biodistribution in relation to tumour detection with 111In-labelled OV-TL 3 F(ab')2 in patients with ovarian cancer.

PubMed

Massuger, L F; Claessens, R A; Kenemans, P; Verheijen, R H; Boerman, O C; Meeuwis, A P; Schijf, C P; Buijs, W C; Hanselaar, T G; Corstens, F H

1991-07-01

The biological behaviour of 111In-labelled OV-TL 3 F(ab')2 was studied in 22 patients with suspected ovarian cancer. After i.v. injection with 140 MBq 111In-OV-TL 3 F(ab')2 (1 mg) blood samples were taken up to 96 h and urine and faeces were collected throughout the whole study. At surgery, 5 to 7 days post-injection, primary and metastatic tumour tissues, as well as fragments of several normal tissues, were removed and 111In uptake was measured. Blood activity disappeared with half-life values of 6.1 +/- 1.1 and 17.9 +/- 6.5 h. Within 96 h excretion in urine and faeces was 16.1 +/- 2.0% i.d. (mean +/- S.D.) and 3.1 +/- 1.9% i.d., respectively. Mean tissue uptake, expressed as % i.d. kg-1 was 3.9 +/- 1.0 for primary tumour, 11.5 +/- 5.0 for liver and 0.4 +/- 0.1 for several normal background tissues. Higher tumour uptake correlated with a higher detection rate at immunoscintigraphy. However, no strict correlation was found between the amount of tumour uptake and the expression of the monoclonal antibody defined OA3 antigen. Quantitation of organ activity, using region of interest analysis, resulted in mean peak organ activities for the liver of 16% i.d., spleen 9% i.d. and kidney 4% i.d. Distribution data indicate that besides specific antibody-antigen interaction several other mechanisms play a role in uptake in tumour and other tissues.

Individual, Family, and Community Environmental Correlates of Obesity in Latino Elementary School Children*

PubMed Central

Elder, John P.; Arredondo, Elva M.; Campbell, Nadia; Baquero, Barbara; Duerksen, Susan; Ayala, Guadalupe; Crespo, Noc C.; Slymen, Donald; McKenzie, Thomas

2015-01-01

BACKGROUND The prevalence of overweight children has reached epidemic proportions, and affects Latinos youth more than other subgroups in the United States. Given the prevalence of obesity and its economic consequences, community health initiatives have shifted toward primary prevention at younger ages. METHODS Data representing all levels of the ecological systems theory were collected using diverse methods. Participants were children enrolled in K-2nd grade and their parents. RESULTS Overweight children were less active compared to normal weight children. The parents of overweight children provided less instrumental support to engage in activity and set fewer limits on their child’s activities. Similarly, parents of overweight children were less likely to control, but more likely to set limits on their child’s diet compared to parents of normal weight children. Parents who rated their health more positively and were less acculturated were more likely to have children who were overweight. School and community level variables were not significantly correlated with children’s weight. Adjusting for the aforementioned variables, parents’ weight status was positively associated with children’s weight. CONCLUSIONS Social and structural environments in which Hispanic children are reared may play an important role in determining their risk for obesity and related behaviors. Parents’ weight was among the strongest correlate of child weight; however, the extent to which this influence functions primarily through biological or social/structural influences is not entirely clear. The role of school and community factors on child’s health practices and body mass index needs to be further examined. PMID:20051087

Traditional and cyberbullying victimization as correlates of psychosocial distress and barriers to a healthy lifestyle among severely obese adolescents – a matched case–control study on prevalence and results from a cross-sectional study

PubMed Central

2014-01-01

Background Obese youth are at increased risk for peer victimization, which may heighten their risk of psychosocial problems and physical activity avoidance, and lower the effectiveness of professional and lifestyle weight-loss initiatives. Little is known about obese adolescents’ risk for victimization from cyber-bullying and how this relates to psychosocial functioning and healthy lifestyle barriers. The purpose of the study was to assess traditional and cyber-victimization among adolescents with severe obesity and its relation to psychosocial distress and barriers to healthy lifestyles. Methods A sample of 102 obese adolescents (mean age = 15.32 ±1.71) in residential treatment was matched with 102 normal-weight youngsters from the Health Behavior in School-aged Children (HBSC) study (mean age = 15.30 ±1.73). Results Adolescents with obesity were significantly more often cyber-victimized than normal-weight peers. Obese youth victimized by traditional bullying experienced lower quality of life, lower motivation for physical activity and higher avoidance and emotional coping towards healthy lifestyles than those non-victimized. Obese cyber-victims experienced significantly higher suicidal ideation. Conclusions Traditional and cyber-victimization may hinder treatment effectiveness and healthy lifestyle change in adolescents with obesity. Health professionals should pro-actively address peer victimization and psychosocial functioning during multidisciplinary obesity treatment. Schools could contribute to a better physical and psychosocial health of obese youth by implementing multi-behavioral health-promotion programs. PMID:24593118

Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk

PubMed Central

Ross, Randal G.; Hunter, Sharon K.; McCarthy, Lizbeth; Beuler, Julie; Hutchison, Amanda K.; Wagner, Brandie D.; Leonard, Sherry; Stevens, Karen E.; Freedman, Robert

2013-01-01

Background Deficient cerebral inhibition is a pathophysiological brain deficit related to poor sensory gating and attention in schizophrenia and other disorders. Cerebral inhibition develops perinatally, influenced by genetic and in utero factors. Amniotic choline activates fetal α7-nicotinic acetylcholine receptors and facilitates development of cerebral inhibition. Increasing this activation may protect infants from future illness by promoting normal brain development. Methods A randomized placebo-controlled clinical trial of dietary phosphatidylcholine supplementation was conducted with 100 healthy pregnant women, who consented to the study at second trimester. Supplementation to twice normal dietary levels for mother or newborn continued through the third postnatal month. All women received dietary advice regardless of treatment. Infants’ electroencephalographic recordings of inhibition of the P50 component of the cerebral evoked response to paired sounds were analyzed. Criterion for inhibition was suppression of the amplitude of the second P50 response by at least half, compared to the first response. Results No adverse effects of choline were observed in maternal health and delivery, birth, or infant development. More choline-treated infants (76%) suppressed the P50 response, compared to placebo-treated infants (43%) at the fifth postnatal week (effect size 0.7). There was no difference at the 13th week. A CHRNA7 genotype associated with schizophrenia diminished P50 inhibition in the placebo-treated infants, but not in the choline-treated infants. Conclusion Neonatal developmental delay in inhibition is associated with attentional problems as the child matures. Perinatal choline activates timely development of cerebral inhibition, even in the presence of gene mutations that otherwise delay it. PMID:23318559

Smooth muscle of telokin-deficient mice exhibits increased sensitivity to Ca2+ and decreased cGMP-induced relaxation.

PubMed

Khromov, A S; Wang, H; Choudhury, N; McDuffie, M; Herring, B P; Nakamoto, R; Owens, G K; Somlyo, A P; Somlyo, A V

2006-02-14

Cyclic nucleotides can relax smooth muscle without a change in [Ca2+]i, a phenomenon termed Ca2+ desensitization, contributing to vasodilation, gastrointestinal motility, and airway resistance. The physiological importance of telokin, a 17-kDa smooth muscle-specific protein and target for cyclic nucleotide-induced Ca2+ desensitization, was determined in telokin null mice bred to a congenic background. Telokin null ileal smooth muscle homogenates compared to wild type exhibited an approximately 30% decrease in myosin light-chain phosphatase (MLCP) activity, which was reflected in a significant leftward shift (up to 2-fold at pCa 6.3) of the Ca2+ force relationship accompanied by an increase in myosin light-chain phosphorylation. No difference in the Ca2+ force relationship occurred in telokin WT and knockout (KO) aortas, presumably reflecting the normally approximately 5-fold lower telokin content in aorta vs. ileum smooth muscle. Ca2+ desensitization of contractile force by 8-Br-cGMP was attenuated by 50% in telokin KO intestinal smooth muscle. The rate of force relaxation reflecting MLCP activity, in the presence of 50 microM 8-Br-cGMP, was also significantly slowed in telokin KO vs. WT ileum and was rescued by recombinant telokin. Normal thick filaments in telokin KO smooth muscles indicate that telokin is not required for filament formation or stability. Results indicate that a primary role of telokin is to modulate force through increasing MLCP activity and that this effect is further potentiated through phosphorylation by cGMP in telokin-rich smooth tissues.

Amplitude-integrated EEG in newborns with critical congenital heart disease predicts preoperative brain magnetic resonance imaging findings.

PubMed

Mulkey, Sarah B; Yap, Vivien L; Bai, Shasha; Ramakrishnaiah, Raghu H; Glasier, Charles M; Bornemeier, Renee A; Schmitz, Michael L; Bhutta, Adnan T

2015-06-01

The study aims are to evaluate cerebral background patterns using amplitude-integrated electroencephalography in newborns with critical congenital heart disease, determine if amplitude-integrated electroencephalography is predictive of preoperative brain injury, and assess the incidence of preoperative seizures. We hypothesize that amplitude-integrated electroencephalography will show abnormal background patterns in the early preoperative period in infants with congenital heart disease that have preoperative brain injury on magnetic resonance imaging. Twenty-four newborns with congenital heart disease requiring surgery at younger than 30 days of age were prospectively enrolled within the first 3 days of age at a tertiary care pediatric hospital. Infants had amplitude-integrated electroencephalography for 24 hours beginning close to birth and preoperative brain magnetic resonance imaging. The amplitude-integrated electroencephalographies were read to determine if the background pattern was normal, mildly abnormal, or severely abnormal. The presence of seizures and sleep-wake cycling were noted. The preoperative brain magnetic resonance imaging scans were used for brain injury and brain atrophy assessment. Fifteen of 24 infants had abnormal amplitude-integrated electroencephalography at 0.71 (0-2) (mean [range]) days of age. In five infants, the background pattern was severely abnormal. (burst suppression and/or continuous low voltage). Of the 15 infants with abnormal amplitude-integrated electroencephalography, 9 (60%) had brain injury. One infant with brain injury had a seizure on amplitude-integrated electroencephalography. A severely abnormal background pattern on amplitude-integrated electroencephalography was associated with brain atrophy (P = 0.03) and absent sleep-wake cycling (P = 0.022). Background cerebral activity is abnormal on amplitude-integrated electroencephalography following birth in newborns with congenital heart disease who have findings of brain injury and/or brain atrophy on preoperative brain magnetic resonance imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

[The genetic background for the eye malformations anophthalmia and microphthalmia].

PubMed

Roos, Laura Sønderberg; Grønskov, Karen; Jensen, Hanne; Tümer, Zeynep

2012-03-12

Anophthalmia and microphthalmia (AO/MO) are rare congenital eye malformations, in which the eyeball is apparently absent or smaller than normal, which causes various degrees of visual impairment. Over 200 different AO/MO-related syndromes have been described, but the genetic background is unknown in many cases. The aim of this article is to give an overview of AO/MO, focusing on the genetic background. It is illustrated that the future identification of new AO/MO related genes will benefit in the genetic counseling of AO/MO patients, and in the understanding of eye development and congenital eye malformations.

Image-processing algorithms for inspecting characteristics of hybrid rice seed

NASA Astrophysics Data System (ADS)

Cheng, Fang; Ying, Yibin

2004-03-01

Incompletely closed glumes, germ and disease are three characteristics of hybrid rice seed. Image-processing algorithms developed to detect these seed characteristics were presented in this paper. The rice seed used for this study involved five varieties of Jinyou402, Shanyou10, Zhongyou207, Jiayou and IIyou. The algorithms were implemented with a 5*600 images set, a 4*400 images set and the other 5*600 images set respectively. The image sets included black background images, white background images and both sides images of rice seed. Results show that the algorithm for inspecting seeds with incompletely closed glumes based on Radon Transform achieved an accuracy of 96% for normal seeds, 92% for seeds with fine fissure and 87% for seeds with unclosed glumes, the algorithm for inspecting germinated seeds on panicle based on PCA and ANN achieved n average accuracy of 98% for normal seeds, 88% for germinated seeds on panicle and the algorithm for inspecting diseased seeds based on color features achieved an accuracy of 92% for normal and healthy seeds, 95% for spot diseased seeds and 83% for severe diseased seeds.

Image quality stability of whole-body diffusion weighted imaging.

PubMed

Chen, Yun-bin; Hu, Chun-miao; Zhong, Jing; Sun, Fei

2009-06-01

To assess the reproducibility of whole-body diffusion weighted imaging (WB-DWI) technique in healthy volunteers under normal breathing with background body signal suppression. WB-DWI was performed on 32 healthy volunteers twice within two-week period using short TI inversion-recovery diffusion-weighted echo-planar imaging sequence and built-in body coil. The volunteers were scanned across six stations continuously covering the entire body from the head to the feet under normal breathing. The bone apparent diffusion coefficient (ADC) and exponential ADC (eADC) of regions of interest (ROIs) were measured. We analyzed correlation of the results using paired-t-test to assess the reproducibility of the WB-DWI technique. We were successful in collecting and analyzing data of 64 WB-DWI images. There was no significant difference in bone ADC and eADC of 824 ROIs between the paired observers and paired scans (P>0.05). Most of the images from all stations were of diagnostic quality. The measurements of bone ADC and eADC have good reproducibility. WB-DWI technique under normal breathing with background body signal suppression is adequate.

Glycolytic potential and activity of adenosine monophosphate kinase (AMPK), glycogen phosphorylase (GP) and glycogen debranching enzyme (GDE) in steer carcasses with normal (<5.8) or high (>5.9) 24h pH determined in M. longissimus dorsi.

PubMed

Apaoblaza, A; Galaz, A; Strobel, P; Ramírez-Reveco, A; Jeréz-Timaure, N; Gallo, C

2015-03-01

Muscle glycogen concentration (MGC) and lactate (LA), activity of glycogen debranching enzyme (GDE), glycogen phosphorylase (GP) and adenosine monophosphate kinase (AMPK) were determined at 0.5h (T0) and 24h (T24) post-mortem in Longissimus dorsi samples from 38 steers that produced high pH (>5.9) and normal pH (<5.8) carcasses at 24h postmortem. MGC, LA and glycolytic potential were higher (P<0.05) in normal pH carcasses. GDE activity was similar (P>0.05) in both pH categories. GP activity increased between T0 and T24 only in normal pH carcasses. AMPK activity was four times higher in normal pH v/s high pH carcasses, without changing its activity over time. Results reinforce the idea that differences in postmortem glycogenolytic/glycolytic flow in L. dorsi of steers showing normal v/s high muscle pH at 24h, could be explained not only by the higher initial MGC in normal pH carcasses, but also by a high and sustained activity of AMPK and an increased GP activity at 24h postmortem. Copyright © 2014 Elsevier Ltd. All rights reserved.

Wound healing activity of Argyreia nervosa leaves extract

PubMed Central

Singhal, AK; Gupta, H; Bhati, VS

2011-01-01

Background: Argyreia nervosa (Convolvulaceae) plant is an example of hallucinogenic plant. The antiseptic, anti-inflammatory, antispasmodic, antibacterial, antiviral, antifungal, anticonvulsant, nootropic, antifertility and aphrodisiac properties have already been reported for this plant. Aim: The aim of present work was to evaluate the wound healing property in normal and diabetic animals by oral and topical administration of ethanolic extract of leaves. Materials and Methods: Phytochemical investigations showed the presence of various biochemicals (alkaloids, flavonoids, carbohydrates, triterpenoids, proteins, saponins, steroids, tannins). A single injection of alloxan monohydrate (120 mg/kg, i.p.) prepared in citrate buffer (0.1 M, pH 4.5) was administered to produce diabetes in rats and mice, after overnight fasting. Excision wounds (sized 300 mm2 and of 2 mm depth) were used for the study of rate of contraction of wound and epithelization. The means of wound area measurement between groups at different time intervalswere compared using one-way analysis of variance (ANOVA), followed by Dunnet's test. Results: Extracts of A. nervosa showed significant wound healing effect in normal (topically treated) and diabetic (both topically and orally treated) rats. In diabetic rats, the topically treated group showed more significant effect than the orally treated groups. Conclusion: The present study demonstrates that A. nervosa leaves extract applied topically promotes healing of wounds more significantly as compared to oral application, in both normal rats and alloxan induced diabetic rats, where healing is otherwise delayed. PMID:23776770

Automatic Mexican sign language and digits recognition using normalized central moments

NASA Astrophysics Data System (ADS)

Solís, Francisco; Martínez, David; Espinosa, Oscar; Toxqui, Carina

2016-09-01

This work presents a framework for automatic Mexican sign language and digits recognition based on computer vision system using normalized central moments and artificial neural networks. Images are captured by digital IP camera, four LED reflectors and a green background in order to reduce computational costs and prevent the use of special gloves. 42 normalized central moments are computed per frame and used in a Multi-Layer Perceptron to recognize each database. Four versions per sign and digit were used in training phase. 93% and 95% of recognition rates were achieved for Mexican sign language and digits respectively.

Aerobic exercise reduces oxidative stress and improves vascular changes of small mesenteric and coronary arteries in hypertension

PubMed Central

Roque, Fernanda R; Briones, Ana M; García-Redondo, Ana B; Galán, María; Martínez-Revelles, Sonia; Avendaño, Maria S; Cachofeiro, Victoria; Fernandes, Tiago; Vassallo, Dalton V; Oliveira, Edilamar M; Salaices, Mercedes

2013-01-01

Background and Purpose Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. We investigated the effects of aerobic exercise training in vascular remodelling and in the mechanical and functional alterations of coronary and small mesenteric arteries from spontaneously hypertensive rats (SHR). Experimental Approach Normotensive Wistar Kyoto (WKY), SHR and SHR trained on a treadmill for 12 weeks were used to evaluate vascular structural, mechanical and functional properties. Key Results Exercise did not affect lumen diameter, wall thickness and wall/lumen ratio but reduced vascular stiffness of coronary and mesenteric arteries from SHR. Exercise also reduced collagen deposition and normalized altered internal elastic lamina organization and expression of MMP-9 in mesenteric arteries from SHR. Exercise did not affect contractile responses of coronary arteries but improved the endothelium-dependent relaxation in SHR. In mesenteric arteries, training normalized the increased contractile responses induced by U46619 and by high concentrations of acetylcholine. In vessels from SHR, exercise normalized the effects of the NADPH oxidase inhibitor apocynin and the NOS inhibitor l-NAME in vasodilator or vasoconstrictor responses, normalized the increased O2− production and the reduced Cu/Zn superoxide dismutase expression and increased NO production. Conclusions and Implications Exercise training of SHR improves endothelial function and vascular stiffness in coronary and small mesenteric arteries. This might be related to the concomitant decrease of oxidative stress and increase of NO bioavailability. Such effects demonstrate the beneficial effects of exercise on the vascular system and could contribute to a reduction in blood pressure. PMID:22994554

Physical activity for campus employees: a university worksite wellness program

PubMed Central

Butler, Carling E.; Clark, B. Ruth; Burlis, Tamara L.; Castillo, Jacqueline C.; Racette, Susan B.

2014-01-01

Background Workplaces provide ideal environments for wellness programming. The purpose of this study was to explore exercise self-efficacy among university employees and the effects of a worksite wellness program on physical activity, cardiorespiratory fitness, and CVD risk factors. Methods Participants included 121 university employees (85% female). The worksite wellness program included cardiovascular health assessments, personal health reports, 8 weeks of pedometer-based walking and tracking activities, and weekly wellness sessions. Daily step count was assessed at baseline, week 4, and week 8. Exercise self-efficacy and CVD risk factors were evaluated at baseline and follow-up. Results Daily step count increased from 6566 ± 258 (LSM ± SE) at baseline to 8605 ± 356 at week 4 and 9107 ± 388 at week 8 (P < .0001). Steps increased among normal weight, overweight, and obese sub-groups. Exercise self-efficacy correlated with baseline steps (P < .05). Small improvements were observed in cardiorespiratory fitness, BMI, blood pressure, blood glucose, total cholesterol, and triglycerides (all P < .01). Conclusions A worksite wellness program was effective for increasing physical activity, cardiorespiratory fitness, and CVD risk factors among university employees. Exercise barriers and outcome expectations were identified and have implications for future worksite wellness programming. PMID:24905703

75 FR 63258 - Vessel Re-Designations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-14

... implementation of the Cargo Preference Act (CPA). The MOU was published in the Federal Register in 74 FR 47308... normal business hours. Background The CPA requires that federal agencies take ``necessary and practicable...

The In Vitro Effect of Acidic-Pepsin on Nuclear Factor KappaB Activation and Its Related Oncogenic Effect on Normal Human Hypopharyngeal Cells

PubMed Central

Sasaki, Clarence T.; Toman, Julia; Vageli, Dimitra

2016-01-01

Background Extra-esophageal carcinogenesis has been widely discussed in relation to the chronic effects of laryngopharyngeal reflux and most prominently with pepsin historically central to this discussion. With refluxate known to include gastric (pepsin) and duodenal (bile) fluids, we recently demonstrated the mechanistic role of NF-κB in mediating the preneoplastic effects of acidic-bile. However, the role of pepsin in promoting hypopharyngeal premalignant events remains historically unclear. Here, we investigate the in vitro effect of acidic-pepsin on the NF-κB oncogenic pathway to better define its potential role in hypopharyngeal neoplasia. Methods Human hypopharyngeal primary cells (HHPC) and keratinocytes (HHK) were repetitively exposed to physiologic pepsin concentrations (0.1 mg/ml) at pH 4.0, 5.0 and 7.0. Cellular localization of phospho-NF-κB and bcl-2 was determined using immunofluorescence and western blotting. NF-κB transcriptional activity was tested by luc reporter and qPCR. Analysis of DNA content of pepsin treated HHK and HHPC was performed using Fluorescence-activated-cell sorting assay. To explore a possible dose related effect, pepsin concentration was reduced from 0.1 to 0.05 and 0.01 mg/ml. Results At physiologic concentration, acidic-pepsin (0.1 mg/ml at pH 4.0) is lethal to most normal hypopharyngeal cells. However, in surviving cells, no NF-κB transcriptional activity is noted. Acidic-pepsin fails to activate the NF-κB or bcl-2, TNF-α, EGFR, STAT3, and wnt5α but increases the Tp53 mRNAs, in both HHPC and HHK. Weakly acidic-pepsin (pH 5.0) and neutral-pepsin (pH 7.0) induce mild activation of NF-κB with increase in TNF-α mRNAs, without oncogenic transcriptional activity. Lower concentrations of pepsin at varying pH do not produce NF-κB activity or transcriptional activation of the analyzed genes. Conclusion Our findings in vitro do not support the role of acidic-pepsin in NF-κB related hypopharyngeal carcinogenesis. PMID:27973541

Technologically Enhanced Naturally Occurring Radioactive Materials (TENORM) in the Oil and Gas Industry: A Review.

PubMed

Doyi, Israel; Essumang, David Kofi; Dampare, Samuel; Glover, Eric Tetteh

Radiation is part of the natural environment: it is estimated that approximately 80 % of all human exposure comes from naturally occurring or background radiation. Certain extractive industries such as mining and oil logging have the potential to increase the risk of radiation exposure to the environment and humans by concentrating the quantities of naturally occurring radiation beyond normal background levels (Azeri-Chirag-Gunashli 2004).

Optimizing the optical wavelength for the photoacoustic imaging of inflammatory arthritis

NASA Astrophysics Data System (ADS)

Jo, Janggun; Xu, Guan; Hu, Jack; Francis, Sheeja; Marquardt, April; Yuan, Jie; Girish, Gandikota; Wang, Xueding

2015-03-01

With the capability of assessing high resolution optical information in soft tissues at imaging depth up to several centimeters, innovative biomedical photoacoustic imaging (PAI) offers benefits to diagnosis and treatment monitoring of inflammatory arthritis, particularly in combination with more established ultrasonography (US). In this work, a PAI and US dual-modality system facilitating both imaging functions in a real-time fashion was developed and initially tested for its clinical performance on patients with active inflammatory arthritis. Photoacoustic (PA) images of metacarpophalangeal (MCP) joints were acquired at 580-nm wavelength that provides a desired balance between optical absorption of blood and attenuation in background tissue. The results from six patients and six normal volunteers used as a control demonstrated the satisfactory sensitivity of PAI in assessing the physiological changes in the joints, specifically enhanced blood flow as a result of active synovitis. This preliminary study suggests that PAI, by revealing vascular features suggestive of joint inflammation, could be a valuable supplement to musculoskeletal US for rheumatology clinic.

SYNAPTIC DEPRESSION IN DEEP NEURAL NETWORKS FOR SPEECH PROCESSING.

PubMed

Zhang, Wenhao; Li, Hanyu; Yang, Minda; Mesgarani, Nima

2016-03-01

A characteristic property of biological neurons is their ability to dynamically change the synaptic efficacy in response to variable input conditions. This mechanism, known as synaptic depression, significantly contributes to the formation of normalized representation of speech features. Synaptic depression also contributes to the robust performance of biological systems. In this paper, we describe how synaptic depression can be modeled and incorporated into deep neural network architectures to improve their generalization ability. We observed that when synaptic depression is added to the hidden layers of a neural network, it reduces the effect of changing background activity in the node activations. In addition, we show that when synaptic depression is included in a deep neural network trained for phoneme classification, the performance of the network improves under noisy conditions not included in the training phase. Our results suggest that more complete neuron models may further reduce the gap between the biological performance and artificial computing, resulting in networks that better generalize to novel signal conditions.

Preparation of Fe3O4 magnetic nanoparticles coated with gallic acid for drug delivery

PubMed Central

Dorniani, Dena; Hussein, Mohd Zobir Bin; Kura, Aminu Umar; Fakurazi, Sharida; Shaari, Abdul Halim; Ahmad, Zalinah

2012-01-01

Background and methods Magnetic iron oxide nanoparticles were prepared using a sonochemical method under atmospheric conditions at a Fe2+ to Fe3+ molar ratio of 1:2. The iron oxide nanoparticles were subsequently coated with chitosan and gallic acid to produce a core-shell structure. Results X-ray diffraction demonstrated that the magnetic nanoparticles were pure Fe3O4 with a cubic inverse spinel structure. Transmission electron microscopy showed that the Fe3O4 nanoparticles were of spherical shape with a mean diameter of 11 nm, compared with 13 nm for the iron oxide-chitosan-gallic acid (FCG) nanocarriers. Conclusion The magnetic nanocarrier enhanced the thermal stability of the drug, gallic acid. Release of the active drug from the FCG nanocarrier was found to occur in a controlled manner. The gallic acid and FCG nanoparticles were not toxic in a normal human fibroblast (3T3) line, and anticancer activity was higher in HT29 than MCF7 cell lines. PMID:23166439

Sensitivity of the normalized difference vegetation index to subpixel canopy cover, soil albedo, and pixel scale

NASA Technical Reports Server (NTRS)

Jasinski, Michael F.

1990-01-01

An analytical framework is provided for examining the physically based behavior of the normalized difference vegetation index (NDVI) in terms of the variability in bulk subpixel landscape components and with respect to variations in pixel scales, within the context of the stochastic-geometric canopy reflectance model. Analysis focuses on regional scale variability in horizontal plant density and soil background reflectance distribution. Modeling is generalized to different plant geometries and solar angles through the use of the nondimensional solar-geometric similarity parameter. Results demonstrate that, for Poisson-distributed plants and for one deterministic distribution, NDVI increases with increasing subpixel fractional canopy amount, decreasing soil background reflectance, and increasing shadows, at least within the limitations of the geometric reflectance model. The NDVI of a pecan orchard and a juniper landscape is presented and discussed.

Comparative analysis of guide mode of government - oriented industry guidance funds under china’s new normal of economic growth

NASA Astrophysics Data System (ADS)

Sun, Chunling; Cheng, Xuemei

2017-11-01

The government-oriented industry guidance Funds solve the problem of financing difficulty and high innovation under the background of China’s new normal. Through the provinces and cities of the policies and regulations of the collation and comparative analysis, it will be divided into three modes. And then compare among three modes and analyze applicability to guide the construction of provinces and cities.

Study of Background Rejection Systems for the IXO Mission.

NASA Astrophysics Data System (ADS)

Laurent, Philippe; Limousin, O.; Tatischeff, V.

2009-01-01

The scientific performances of the IXO mission will necessitate a very low detector background level. This will imply thorough background simulations, and efficient background rejection systems. It necessitates also a very good knowledge of the detectors to be shielded. In APC, Paris, and CEA, Saclay, we got experience on these activities by conceiving and optimising in parallel the high energy detector and the active and passive background rejection system of the Simbol-X mission. Considering that this work may be naturally extended to other X-ray missions, we have initiated with CNES a R&D project on the study of background rejection systems mainly in view the IXO project. We will detail this activity in the poster.

Differentiation of specific ripple patterns helps to identify epileptogenic areas for surgical procedures.

PubMed

Kerber, Karolin; Dümpelmann, Matthias; Schelter, Björn; Le Van, Pierre; Korinthenberg, Rudolf; Schulze-Bonhage, Andreas; Jacobs, Julia

2014-07-01

High frequency oscillations (HFOs) at 80-500 Hz are promising markers of epileptic areas. Several retrospective studies reported that surgical removal of areas generating HFOs was associated with a good seizure outcome. Recent reports suggested that ripple (80-200 Hz) HFO patterns co-existed with different background EEG activities. We hypothesized that the coexisting background EEG pattern may distinguish physiological from epileptic ripples. Rates of HFOs were analyzed in intracranial EEG recordings of 22 patients. Additionally, ripple patterns were classified for each channel depending either as coexisting with a flat or oscillatory background activity. A multi-variate analysis was performed to determine whether removal of areas showing the above EEG markers correlated with seizure outcome. Removal of areas generating high rates of 'fast ripples (>200 Hz)' and 'ripples on a flat background activity' showed a significant correlation with a seizure-free outcome. In contrast, removal of high rates of 'ripples' or 'ripple patterns in a continuously oscillating background' was not significantly associated with seizure outcome. Ripples occurring in an oscillatory background activity may be suggestive of physiological activity, while those on a flat background reflect epileptic activity. Consideration of coexisting background patterns may improve the delineation of the epileptogenic areas using ripple oscillations. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A pilot crossover study: effects of an intervention using an activity monitor with computerized game functions on physical activity and body composition.

PubMed

Nishiwaki, Masato; Kuriyama, Akinori; Ikegami, Yumi; Nakashima, Nana; Matsumoto, Naoyuki

2014-12-02

Wearing an activity monitor as a motivational tool and incorporating a behavior-based reward system or a computerized game element might have a synergistic effect on an increase in daily physical activity, thereby inducing body fat reduction. This pilot crossover study aimed to examine the effects of a short-term lifestyle intervention using an activity monitor with computerized game functions on physical activity and body composition. Twenty healthy volunteers (31 ± 3 years) participated in a 12-week crossover study. The participants were randomly assigned to either Group A (a 6-week game intervention followed by a 6-week normal intervention) or Group B (a 6-week normal intervention followed by a 6-week game intervention). The participants wore both a normal activity monitor (Lifecorder EX) and an activity monitor with computerized game functions (Yuuhokei) during the game intervention, whereas they only wore a normal activity monitor during the normal intervention. Before, during, and after the intervention, body composition was assessed. Significantly more daily steps were recorded for the game intervention than for the normal intervention (10,520 ± 562 versus 8,711 ± 523 steps/day, P < 0.01). The participants performed significantly more physical activity at an intensity of ≥ 3 metabolic equivalents (METs) in the game intervention than in the normal intervention (3.1 ± 0.2 versus 2.4 ± 0.2 METs · hour/day, P < 0.01). Although body mass and fat were significantly reduced in both periods (P < 0.01), the difference in body fat reduction was significantly greater in the game intervention than in the normal intervention (P < 0.05). A short-term intervention using an activity monitor with computerized game functions increases physical activity and reduces body fat more effectively than an intervention using a standard activity monitor.

The psychometric properties of the Chinese version-reintegration to normal living index (C-RNLI) for identifying participation restriction among community-dwelling frail older people.

PubMed

Liu, Justina Yat-Wa; Ma, Ka Wai

2017-01-31

The Reintegration to Normal Living Index (RNLI) was developed to measure reintegration to normal living after major traumas/illnesses. Its psychometric properties remain unknown when used to measure participation restriction under the World Health Organization's International Classification of Functioning, Disability, and Health (WHO-ICF) framework. This study examines the psychometric properties of the Chinese version-RNLI to measure WHO-ICF participation restriction among community-dwelling pre-frail and frail older people. A cross-sectional study was conducted in community and day-care centres in Hong Kong between May 2015 and January 2016. Through face-to-face interviews, information was collected on the participants' demographic background, medical history, frailty status, depressive mood, functional performance in daily activities, and participation restriction. The internal consistency, test-retest reliability, and construct and convergent validity of the C-RNLI were assessed. Two hundred and ninety-nine pre-frail or frail community-dwelling older people with a mean age of 79.53 were recruited. A confirmatory factor analysis showed that the C-RNLI has a two-factor structure comprised of "participation in physical activities" and "participation in social events". The test-retest coefficient was 0.71. The Cronbach's alpha of the total C-RNLI score, and those of the factors "participation in physical activities" and "participation in social events" were 0.88, 0.82 and 0.84, respectively. Pre-frail older people had significantly higher scores for the factors "participation in physical activities" (z = -5.05, <0.01) and "participation in social events" (z = -6.04, p < 0.01) than frail older people. Older people from community centres had significantly higher scores for the factors "participation in physical activities" (z = -4.48, <0.01) and "participation in social events" (z = -4.03, p < 0.01) than older people from day-care centres. The factors "participation in physical activities" and "participation in social events" of the C-RNLI were significantly convergent with depressive mood (r s  = -0.25 and r s  = -0.39, respectively) and functional performance in daily activities (r s  = 0.28 and r s  = 0.45, respectively). The C-RNLI is a two-factor structured scale with acceptable level of reliability and validity to measure WHO-ICF participation restriction among community-dwelling pre-frail and frail older people.

A novel transferrin receptor-targeted hybrid peptide disintegrates cancer cell membrane to induce rapid killing of cancer cells

PubMed Central

2011-01-01

Background Transferrin receptor (TfR) is a cell membrane-associated glycoprotein involved in the cellular uptake of iron and the regulation of cell growth. Recent studies have shown the elevated expression levels of TfR on cancer cells compared with normal cells. The elevated expression levels of this receptor in malignancies, which is the accessible extracellular protein, can be a fascinating target for the treatment of cancer. We have recently designed novel type of immunotoxin, termed "hybrid peptide", which is chemically synthesized and is composed of target-binding peptide and lytic peptide containing cationic-rich amino acids components that disintegrates the cell membrane for the cancer cell killing. The lytic peptide is newly designed to induce rapid killing of cancer cells due to conformational change. In this study, we designed TfR binding peptide connected with this novel lytic peptide and assessed the cytotoxic activity in vitro and in vivo. Methods In vitro: We assessed the cytotoxicity of TfR-lytic hybrid peptide for 12 cancer and 2 normal cell lines. The specificity for TfR is demonstrated by competitive assay using TfR antibody and siRNA. In addition, we performed analysis of confocal fluorescence microscopy and apoptosis assay by Annexin-V binding, caspase activity, and JC-1 staining to assess the change in mitochondria membrane potential. In vivo: TfR-lytic was administered intravenously in an athymic mice model with MDA-MB-231 cells. After three weeks tumor sections were histologically analyzed. Results The TfR-lytic hybrid peptide showed cytotoxic activity in 12 cancer cell lines, with IC50 values as low as 4.0-9.3 μM. Normal cells were less sensitive to this molecule, with IC50 values > 50 μM. Competition assay using TfR antibody and knockdown of this receptor by siRNA confirmed the specificity of the TfR-lytic hybrid peptide. In addition, it was revealed that this molecule can disintegrate the cell membrane of T47D cancer cells just in 10 min, to effectively kill these cells and induce approximately 80% apoptotic cell death but not in normal cells. The intravenous administration of TfR-lytic peptide in the athymic mice model significantly inhibited tumor progression. Conclusions TfR-lytic peptide might provide a potent and selective anticancer therapy for patients. PMID:21849092

Morphometry, ultrastructure, myosin isoforms, and metabolic capacities of the "mini muscles" favoured by selection for high activity in house mice.

PubMed

Guderley, Helga; Houle-Leroy, Philippe; Diffee, Gary M; Camp, Dana M; Garland, Theodore

2006-07-01

Prolonged selective breeding of mice (Mus musculus) for high levels of voluntary wheel running has favoured an unusual phenotype ("mini muscles"), apparently caused by a single Mendelian recessive allele, in which most hind-limb muscles are markedly reduced in mass, but have increased mass-specific activities of mitochondrial enzymes. We examined whether these changes reflect changes in fibre size, number or ultrastructure in normal and "mini-muscle" mice within the two (of four) selectively bred lines (lab designations L3 and L6) that exhibit the phenotype at generations 26 and 27. In both lines, the gastrocnemius and plantaris muscles are smaller in mass (by >50% and 20%, respectively) in affected individuals. The mass-specific activities of mitochondrial enzymes in the gastrocnemius and plantaris muscles were increased in the mini phenotype in both lines, with stronger effects in the gastrocnemius muscle. In the gastrocnemius, the % myosin heavy chain (MHC) IIb was reduced by 50% in L3 and by 30% in L6, whereas the % MHC IIa and I were higher, particularly in L3. Fibre number in the plantaris muscle did not significantly differ between mini and normal muscles, although muscle mass was a significant positive correlate of fibre number. Small fibres were more abundant in mini than normal muscles in L3. Mitochondrial volume density was significantly higher in mini than normal muscle fibres in L3, but not in L6. Microscopy revealed a surprising attribute of the mini muscles: an abundance of small, minimally differentiated, myofibril-containing cells positioned in a disorderly fashion, particularly in the surface layer. We hypothesise that these unusual cells may be satellite cells or type IIb fibres that did not complete their differentiation. Together, these observations suggest that mice with the mini phenotype have reduced numbers of type IIb fibres in many of their hind-limb muscles, leading to a decrease in mass and an increase in mass-specific aerobic capacity in muscles that typically have a high proportion of type IIb fibres. Moreover, the several statistically significant interactions between muscle phenotype and line indicate that the effect of the underlying allele is altered by genetic background.

Targeting MET kinase with the small-molecule inhibitor amuvatinib induces cytotoxicity in primary myeloma cells and cell lines

PubMed Central

2013-01-01

Background MET is a receptor tyrosine kinase that is activated by the ligand HGF and this pathway promotes cell survival, migration, and motility. In accordance with its oncogenic role, MET is constitutively active, mutated, or over-expressed in many cancers. Corollary to its impact, inhibition of MET kinase activity causes reduction of the downstream signaling and demise of cells. In myeloma, a B-cell plasma malignancy, MET is neither mutated nor over-expressed, however, HGF is increased in plasma or serum obtained from myeloma patients and this was associated with poor prognosis. The small-molecule, amuvatinib, inhibits MET receptor tyrosine kinase. Based on this background, we hypothesized that targeting the HGF/MET signaling pathway is a rational approach to myeloma therapy and that myeloma cells would be sensitive to amuvatinib. Methods Expression of MET and HGF mRNAs in normal versus malignant plasma cells was compared during disease progression. Cell death and growth as well as MET signaling pathway were assessed in amuvatinib treated primary myeloma cells and cell lines. Results There was a progressive increase in the transcript levels of HGF (but not MET) from normal plasma cells to refractory malignant plasma cells. Amuvatinib readily inhibited MET phosphorylation in primary CD138+ cells from myeloma patients and in concordance, increased cell death. A 48-hr amuvatinib treatment in high HGF-expressing myeloma cell line, U266, resulted in growth inhibition. Levels of cytotoxicity were time-dependent; at 24, 48, and 72 h, amuvatinib (25 μM) resulted in 28%, 40%, and 55% cell death. Consistent with these data, there was an amuvatinib-mediated decrease in MET phosphorylation in the cell line. Amuvatinib at concentrations of 5, 10, or 25 μM readily inhibited HGF-dependent MET, AKT, ERK and GSK-3-beta phosphorylation. MET-mediated effects were not observed in myeloma cell line that has low MET and/or HGF expression. Conclusions These data suggest that at the cellular level MET/HGF pathway inclines with myeloma disease progression. Amuvatinib, a small molecule MET kinase inhibitor, is effective in inducing growth inhibition and cell death in myeloma cell lines as well as primary malignant plasma cells. These cytostatic and cytotoxic effects were associated with an impact on MET/HGF pathway. PMID:24326130

Tinnitus Perception and Distress Is Related to Abnormal Spontaneous Brain Activity as Measured by Magnetoencephalography

PubMed Central

Weisz, Nathan; Moratti, Stephan; Meinzer, Marcus; Dohrmann, Katalin; Elbert, Thomas

2005-01-01

Background The neurophysiological mechanisms underlying tinnitus perception are not well understood. Surprisingly, there have been no group studies comparing abnormalities in ongoing, spontaneous neuronal activity in individuals with and without tinnitus perception. Methods and Findings Here, we show that the spontaneous neuronal activity of a group of individuals with tinnitus (n = 17) is characterised by a marked reduction in alpha (8–12 Hz) power together with an enhancement in delta (1.5–4 Hz) as compared to a normal hearing control group (n = 16). This pattern was especially pronounced for temporal regions. Moreover, correlations with tinnitus-related distress revealed strong associations with this abnormal spontaneous activity pattern, particularly in right temporal and left frontal areas. Overall, effects were stronger for the alpha than for the delta frequency band. A data stream of 5 min, recorded with a whole-head neuromagnetometer under a resting condition, was sufficient to extract the marked differences. Conclusions Despite some limitations, there are arguments that the regional pattern of abnormal spontaneous activity we found could reflect a tinnitus-related cortical network. This finding, which suggests that a neurofeedback approach could reduce the adverse effects of this disturbing condition, could have important implications for the treatment of tinnitus. PMID:15971936

Dual luciferase assay for secreted luciferases based on Gaussia and NanoLuc.

PubMed

Heise, Kerstin; Oppermann, Henry; Meixensberger, Jürgen; Gebhardt, Rolf; Gaunitz, Frank

2013-05-01

Just recently, NanoLuc, a new engineered luciferase based on the small subunit of the luciferase from Oplophorus gracilirostris was introduced. Like the luciferase from Gaussia princeps, this luciferase is secreted into the medium. Both luciferases are the smallest and brightest luciferases known and well-suited for reporter assays. In our experiments, we demonstrate that both luciferases can be used together in a dual-reporter assay by solving the problem that NanoLuc produces a significant signal with coelenterazine, which is the substrate for Gaussia luciferase. We found that the background signal from NanoLuc with coelenterazine can be calculated from the determination of NanoLuc activity in the presence of its substrate furimazine. This in turn allows the precise determination of the activity of Gaussia which does not produce light in the presence of furimazine. Based on this observation, we developed a high sensitive dual secreted luciferase assay which allows the determination of both activities in a single cotransfection experiment. We demonstrate the versatility and robustness of the assay for the normalization of reporter gene activities. Since Gaussia luciferase and NanoLuc are nonhomologous reporters, the method to determine both luciferase activities may also be useful for coincidence reporter gene systems for high-throughput screening.

The health-related quality of life among pre-diabetics and its association with body mass index and physical activity in a semi-urban community in Malaysia- a cross sectional study

PubMed Central

2014-01-01

Background People with pre-diabetes are at high risk of developing type 2 diabetes and cardiovascular diseases. Measurements of health-related quality of life (HRQOL) among pre-diabetics enable the health care providers to understand their overall health status and planning of interventions to prevent type 2 diabetes. Therefore we aimed to determine the HRQOL and physical activity level; and its association with Body Mass Index (BMI) among pre-diabetics. Methods This was a cross sectional study carried out in two primary care clinics in a semi-urban locality of Ampangan, Negeri Sembilan, Malaysia. Data was collected through self-administered questionnaires assessing the demographic characteristics, medical history, lifestyle and physical activity. The Short Form 36-items health survey was used to measure HRQOL among the pre-diabetics. Data entry and analysis were performed using the SPSS version 19. Results A total of 268 eligible pre-diabetics participated in this study. The prevalence of normal weight, overweight and obesity were 7.1%, 21.6% and 71.3% respectively. Their mean (SD) age was 52.5 (8.3) years and 64.2% were females. Among the obese pre-diabetics, 42.2% had both IFG and IGT, 47.0% had isolated IFG and 10.8% had isolated IGT, 36.2% had combination of hypertension, dyslipidemia and musculoskeletal diseases. More than 53.4% of the obese pre-diabetics had family history of diabetes, 15.7% were smokers and 60.8% were physically inactive with mean PA of < 600 MET-minutes/week. After adjusted for co-variants, Physical Component Summary (PCS) was significantly associated with BMI categories [F (2,262) = 11.73, p < 0.001] where pre-diabetics with normal weight and overweight had significantly higher PCS than those obese; normal vs obese [Mdiff = 9.84, p = 0.006, 95% CIdiff = 2.28, 17.40] and between overweight vs obese [Mdiff = 8.14, p < 0.001, 95% CIdiff = 3.46, 12.80]. Conclusion Pre-diabetics who were of normal weight reported higher HRQOL compared to those overweight and obese. These results suggest a potentially greater risk of poor HRQOL among pre-diabetics who were overweight and obese especially with regard to the physical health component. Promoting recommended amount of physical activity and weight control are particularly important interventions for pre-diabetics at the primary care level. PMID:24684809

76 FR 65749 - Importer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-24

... treatment of wounds which contains trace amounts of the controlled substances normally found in poppy straw... the company's compliance with state and local laws, and a review of the company's background and...

Thioacetamide-induced cirrhosis in selenium-adequate mice displays rapid and persistent abnormity of hepatic selenoenzymes which are mute to selenium supplementation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Jinsong; Wang Huali; Yu Hanqing

2007-10-01

Selenium reduction in cirrhosis is frequently reported. The known beneficial effect of selenium supplementation on cirrhosis is probably obtained from nutritionally selenium-deficient subjects. Whether selenium supplementation truly improves cirrhosis in general needs additional experimental investigation. Thioacetamide was used to induce cirrhosis in selenium-adequate and -deficient mice. Selenoenzyme activity and selenium content were measured and the influence of selenium supplementation was evaluated. In Se-adequate mice, thioacetamide-mediated rapid onset of hepatic oxidative stress resulted in an increase in thioredoxin reductase activity and a decrease in both glutathione peroxidase activity and selenium content. The inverse activity of selenoenzymes (i.e. TrxR activity goes upmore » and GPx activity goes down) was persistent and mute to selenium supplementation during the progress of cirrhosis; accordingly, cirrhosis was not improved by selenium supplementation in any period. On the other hand, selenium supplementation to selenium-deficient mice always more efficiently increased hepatic glutathione peroxidase activity and selenium content compared with those treated with thioacetamide, indicating that thioacetamide impairs the liver bioavailability of selenium. Although thioacetamide profoundly affects hepatic selenium status in selenium-adequate mice, selenium supplementation does not modify the changes. Selenium supplementation to cirrhotic subjects with a background of nutritional selenium deficiency can improve selenium status but cannot restore hepatic glutathione peroxidase and selenium to normal levels.« less

Comprehensive behavioral analysis of pituitary adenylate cyclase-activating polypeptide (PACAP) knockout mice

PubMed Central

Hattori, Satoko; Takao, Keizo; Tanda, Koichi; Toyama, Keiko; Shintani, Norihito; Baba, Akemichi; Hashimoto, Hitoshi; Miyakawa, Tsuyoshi

2012-01-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide acting as a neurotransmitter, neuromodulator, or neurotrophic factor. PACAP is widely expressed throughout the brain and exerts its functions through the PACAP-specific receptor (PAC1). Recent studies reveal that genetic variants of the PACAP and PAC1 genes are associated with mental disorders, and several behavioral abnormalities of PACAP knockout (KO) mice are reported. However, an insufficient number of backcrosses was made using PACAP KO mice on the C57BL/6J background due to their postnatal mortality. To elucidate the effects of PACAP on neuropsychiatric function, the PACAP gene was knocked out in F1 hybrid mice (C57BL/6J × 129SvEv) for appropriate control of the genetic background. The PACAP KO mice were then subjected to a behavioral test battery. PACAP deficiency had no significant effects on neurological screen. As shown previously, the mice exhibited significantly increased locomotor activity in a novel environment and abnormal anxiety-like behavior, while no obvious differences between genotypes were shown in home cage (HC) activity. In contrast to previous reports, the PACAP KO mice showed normal prepulse inhibition (PPI) and slightly decreased depression-like behavior. Previous study demonstrates that the social interaction (SI) in a resident-intruder test was decreased in PACAP KO mice. On the other hand, we showed that PACAP KO mice exhibited increased SI in Crawley's three-chamber social approach test, although PACAP KO had no significant impact on SI in a HC. PACAP KO mice also exhibited mild performance deficit in working memory in an eight-arm radial maze (RM) and the T-maze (TM), while they did not show any significant abnormalities in the left-right discrimination task in the TM. These results suggest that PACAP has an important role in the regulation of locomotor activity, social behavior, anxiety-like behavior and, potentially, working memory. PMID:23060763

The Effects of Musical and Linguistic Components in Recognition of Real-World Musical Excerpts by Cochlear Implant Recipients and Normal-Hearing Adults

PubMed Central

Gfeller, Kate; Jiang, Dingfeng; Oleson, Jacob; Driscoll, Virginia; Olszewski, Carol; Knutson, John F.; Turner, Christopher; Gantz, Bruce

2011-01-01

Background Cochlear implants (CI) are effective in transmitting salient features of speech, especially in quiet, but current CI technology is not well suited in transmission of key musical structures (e.g., melody, timbre). It is possible, however, that sung lyrics, which are commonly heard in real-world music may provide acoustical cues that support better music perception. Objective The purpose of this study was to examine how accurately adults who use CIs (n=87) and those with normal hearing (NH) (n=17) are able to recognize real-world music excerpts based upon musical and linguistic (lyrics) cues. Results CI recipients were significantly less accurate than NH listeners on recognition of real-world music with or, in particular, without lyrics; however, CI recipients whose devices transmitted acoustic plus electric stimulation were more accurate than CI recipients reliant upon electric stimulation alone (particularly items without linguistic cues). Recognition by CI recipients improved as a function of linguistic cues. Methods Participants were tested on melody recognition of complex melodies (pop, country, classical styles). Results were analyzed as a function of: hearing status and history, device type (electric only or acoustic plus electric stimulation), musical style, linguistic and musical cues, speech perception scores, cognitive processing, music background, age, and in relation to self-report on listening acuity and enjoyment. Age at time of testing was negatively correlated with recognition performance. Conclusions These results have practical implications regarding successful participation of CI users in music-based activities that include recognition and accurate perception of real-world songs (e.g., reminiscence, lyric analysis, listening for enjoyment). PMID:22803258

Importance of Real-Time Assays To Distinguish Multidrug Efflux Pump-Inhibiting and Outer Membrane-Destabilizing Activities in Escherichia coli.

PubMed

Misra, Rajeev; Morrison, Keith D; Cho, Hyun Jae; Khuu, Thanh

2015-08-01

The constitutively expressed AcrAB multidrug efflux system of Escherichia coli shows a high degree of homology with the normally silent AcrEF system. Exposure of a strain with acrAB deleted to antibiotic selection pressure frequently leads to the insertion sequence-mediated activation of the homologous AcrEF system. In this study, we used strains constitutively expressing either AcrAB or AcrEF from their normal chromosomal locations to resolve a controversy about whether phenylalanylarginine β-naphthylamide (PAβN) inhibits the activities of AcrAB and AcrEF and/or acts synergistically with antibiotics by destabilizing the outer membrane permeability barrier. Real-time efflux assays allowed a clear distinction between the efflux pump-inhibiting activity of PAβN and the outer membrane-destabilizing action of polymyxin B nonapeptide (PMXBN). When added in equal amounts, PAβN, but not PMXBN, strongly inhibited the efflux activities of both AcrAB and AcrEF pumps. In contrast, when outer membrane destabilization was assessed by the nitrocefin hydrolysis assay, PMXBN exerted a much greater damaging effect than PAβN. Strong action of PAβN in inhibiting efflux activity compared to its weak action in destabilizing the outer membrane permeability barrier suggests that PAβN acts mainly by inhibiting efflux pumps. We concluded that at low concentrations, PAβN acts specifically as an inhibitor of both AcrAB and AcrEF efflux pumps; however, at high concentrations, PAβN in the efflux-proficient background not only inhibits efflux pump activity but also destabilizes the membrane. The effects of PAβN on membrane integrity are compounded in cells unable to extrude PAβN. The increase in multidrug-resistant bacterial pathogens at an alarming rate has accelerated the need for implementation of better antimicrobial stewardship, discovery of new antibiotics, and deeper understanding of the mechanism of drug resistance. The work carried out in this study highlights the importance of employing real-time fluorescence-based assays in differentiating multidrug efflux-inhibitory and outer membrane-destabilizing activities of antibacterial compounds. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Quantitative Biology of Exercise-Induced Signal Transduction Pathways.

PubMed

Liu, Timon Cheng-Yi; Liu, Gang; Hu, Shao-Juan; Zhu, Ling; Yang, Xiang-Bo; Zhang, Quan-Guang

2017-01-01

Exercise is essential in regulating energy metabolism. Exercise activates cellular, molecular, and biochemical pathways with regulatory roles in training response adaptation. Among them, endurance/strength training of an individual has been shown to activate its respective signal transduction pathways in skeletal muscle. This was further studied from the viewpoint of quantitative difference (QD). For the mean values, [Formula: see text], of two sets of data, their QD is defined as [Formula: see text] ([Formula: see text]). The function-specific homeostasis (FSH) of a function of a biosystem is a negative-feedback response of the biosystem to maintain the function-specific conditions inside the biosystem so that the function is perfectly performed. A function in/far from its FSH is called a normal/dysfunctional function. A cellular normal function can resist the activation of other signal transduction pathways so that there are normal function-specific signal transduction pathways which full activation maintains the normal function. An acute endurance/strength training may be dysfunctional, but its regular training may be normal. The normal endurance/strength training of an individual may resist the activation of other signal transduction pathways in skeletal muscle so that there may be normal endurance/strength training-specific signal transduction pathways (NEPs/NSPs) in skeletal muscle. The endurance/strength training may activate NSPs/NEPs, but the QD from the control is smaller than 0.80. The simultaneous activation of both NSPs and NEPs may enhance their respective activation, and the QD from the control is larger than 0.80. The low level laser irradiation pretreatment of rats may promote the activation of NSPs in endurance training skeletal muscle. There may be NEPs/NSPs in skeletal muscle trained by normal endurance/strength training.

Activation of chloride channels in normal and cystic fibrosis airway epithelial cells by multifunctional calcium/calmodulin-dependent protein kinase

NASA Astrophysics Data System (ADS)

Wagner, John A.; Cozens, Alison L.; Schulman, Howard; Gruenert, Dieter C.; Stryer, Lubert; Gardner, Phyllis

1991-02-01

CYSTIC fibrosis is associated with defective regulation of apical membrane chloride channels in airway epithelial cells. These channels in normal cells are activated by cyclic AMP-dependent protein kinase1,2 and protein kinase C3,4. In cystic fibrosis these kinases fail to activate otherwise normal Cl- channels1-4. But Cl- flux in cystic fibrosis cells, as in normal cells, can be activated by raising intracellular Ca2+ (refs 5-10). We report here whole-cell patch clamp studies of normal and cystic fibrosis-derived airway epithelial cells showing that Cl- channel activation by Ca2+ is mediated by multifunctional Ca2+/calmodulin-dependent protein kinase. We find that intracellular application of activated kinase and ATP activates a Cl- current similar to that activated by a Ca2+ ionophore, that peptide inhibitors of either the kinase or calmodulin block Ca2+-dependent activation of Cl- channels, and that a peptide inhibitor of protein kinase C does not block Ca2+-dependent activation. Ca2+/calmodulin activation of Cl- channels presents a pathway with therapeutic potential for circumventing defective regulation of Cl- channels in cystic fibrosis.

Subjective and psychophysiological indices of listening effort in a competing-talker task

PubMed Central

Mackersie, Carol L.; Cones, Heather

2010-01-01

Background The effects of noise and other competing backgrounds on speech recognition performance are well documented. There is less information, however, on listening effort and stress experienced by listeners during a speech recognition task that requires inhibition of competing sounds. Purpose The purpose was a) to determine if psychophysiological indices of listening effort were more sensitive than performance measures (percentage correct) obtained near ceiling level during a competing speech task b) to determine the relative sensitivity of four psychophysiological measures to changes in task demand and c) to determine the relationships between changes in psychophysiological measures and changes in subjective ratings of stress and workload. Research Design A repeated-measures experimental design was used to examine changes in performance, psychophysiological measures, and subjective ratings in response to increasing task demand. Study Sample Fifteen adults with normal hearing participated in the study. The mean age of the participants was 27 (range: 24–54). Data Collection and Analysis Psychophysiological recordings of heart rate, skin conductance, skin temperature, and electromyographic activity (EMG) were obtained during listening tasks of varying demand. Materials from the Dichotic Digits Test were used to modulate task demand. The three levels of tasks demand were: single digits presented to one ear (low-demand reference condition), single digits presented simultaneously to both ears (medium demand), and a series of two digits presented simultaneously to both ears (high demand). Participants were asked to repeat all the digits they heard while psychophysiological activity was recorded simultaneously. Subjective ratings of task load were obtained after each condition using the NASA-TLX questionnaire. Repeated-measures analyses of variance were completed for each measure using task demand and session as factors. Results Mean performance was higher than 96% for all listening tasks. There was no significant change in performance across listening conditions for any listener. There was, however, a significant increase in mean skin conductance and EMG activity as task demand increased. Heart rate and skin temperature did not change significantly. There was no strong association between subjective and psychophysiological measures, but all participants with mean normalized effort ratings of greater than 4.5 (i.e. effort increased by a factor of at least 4.5) showed significant changes in skin conductance. Conclusions Even in the absence of substantial performance changes, listeners may experience changes in subjective and psychophysiological responses consistent with activation of a stress response. Skin conductance appears to be the most promising measure for evaluating individual changes in psychophysiological responses during listening tasks. PMID:21463566

Studies of EBV-lymphoid cell interactions in two patients with the X-linked lymphoproliferative syndrome: normal EBV-specific HLA-restricted cytotoxicity.

PubMed

Rousset, F; Souillet, G; Roncarolo, M G; Lamelin, J P

1986-02-01

Two X-linked lymphoproliferative syndrome (XLP) patients with the hypogammaglobulinemia phenotype were investigated at a time remote from their primary infection with the Epstein-Barr virus (EBV). The lymphoblastoid cell lines derived from these patients expressed the phenotypic markers characteristic of normal mature B lymphocytes and produced normal levels of immunoglobulins (Ig). These observations imply that at least some of their B cells are phenotypically normal. The natural killer (NK) activity of the two patients was low. In one patient, activated lymphocyte killer (ALK) activity was inefficient. These two XLP patients expressed a normal EBV-specific, HLA-restricted cytotoxic activity. It thus appears, from the present findings and those in cases published previously (6/11 patients expressing normal EBV-specific cytotoxic activity), that the notion of poor specific T cell memory for EBV may not be as pivotal ass suggested or, alternatively, that this defect may not be common in hypogammaglobulinemic survivors.

The validity and reliability of a novel activity monitor as a measure of walking

PubMed Central

Ryan, C G; Grant, P M; Tigbe, W W; Granat, M H

2006-01-01

Background The accurate measurement of physical activity is crucial to understanding the relationship between physical activity and disease prevention and treatment. Objective The primary purpose of this study was to investigate the validity and reliability of the activPAL physical activity monitor in measuring step number and cadence. Methods The ability of the activPAL monitor to measure step number and cadence in 20 healthy adults (age 34.5±6.9 years; BMI 26.8±4.8 (mean±SD)) was evaluated against video observation. Concurrently, the accuracy of two commonly used pedometers, the Yamax Digi‐Walker SW‐200 and the Omron HJ‐109‐E, was compared to observation for measuring step number. Participants walked on a treadmill at five different speeds (0.90, 1.12, 1.33, 1.56, and 1.78 m/s) and outdoors at three self selected speeds (slow, normal, and fast). Results At all speeds, inter device reliability was excellent for the activPAL (ICC (2,1)⩾0.99) for both step number and cadence. The absolute percentage error for the activPAL was <1.11% for step number and cadence regardless of walking speed. The accuracy of the pedometers was adversely affected by slow walking speeds. Conclusion The activPAL monitor is a valid and reliable measure of walking in healthy adults. Its accuracy is not influenced by walking speed. The activPAL may be a useful device in sports medicine. PMID:16825270

Development of Trivia Game for speech understanding in background noise.

PubMed

Schwartz, Kathryn; Ringleb, Stacie I; Sandberg, Hilary; Raymer, Anastasia; Watson, Ginger S

2015-01-01

Listening in noise is an everyday activity and poses a challenge for many people. To improve the ability to understand speech in noise, a computerized auditory rehabilitation game was developed. In Trivia Game players are challenged to answer trivia questions spoken aloud. As players progress through the game, the level of background noise increases. A study using Trivia Game was conducted as a proof-of-concept investigation in healthy participants. College students with normal hearing were randomly assigned to a control (n = 13) or a treatment (n = 14) group. Treatment participants played Trivia Game 12 times over a 4-week period. All participants completed objective (auditory-only and audiovisual formats) and subjective listening in noise measures at baseline and 4 weeks later. There were no statistical differences between the groups at baseline. At post-test, the treatment group significantly improved their overall speech understanding in noise in the audiovisual condition and reported significant benefits in their functional listening abilities. Playing Trivia Game improved speech understanding in noise in healthy listeners. Significant findings for the audiovisual condition suggest that participants improved face-reading abilities. Trivia Game may be a platform for investigating changes in speech understanding in individuals with sensory, linguistic and cognitive impairments.

The Effect of the Visual Context in the Recognition of Symbolic Gestures

PubMed Central

Villarreal, Mirta F.; Fridman, Esteban A.; Leiguarda, Ramón C.

2012-01-01

Background To investigate, by means of fMRI, the influence of the visual environment in the process of symbolic gesture recognition. Emblems are semiotic gestures that use movements or hand postures to symbolically encode and communicate meaning, independently of language. They often require contextual information to be correctly understood. Until now, observation of symbolic gestures was studied against a blank background where the meaning and intentionality of the gesture was not fulfilled. Methodology/Principal Findings Normal subjects were scanned while observing short videos of an individual performing symbolic gesture with or without the corresponding visual context and the context scenes without gestures. The comparison between gestures regardless of the context demonstrated increased activity in the inferior frontal gyrus, the superior parietal cortex and the temporoparietal junction in the right hemisphere and the precuneus and posterior cingulate bilaterally, while the comparison between context and gestures alone did not recruit any of these regions. Conclusions/Significance These areas seem to be crucial for the inference of intentions in symbolic gestures observed in their natural context and represent an interrelated network formed by components of the putative human neuron mirror system as well as the mentalizing system. PMID:22363406

Alfven wave refraction by interplanetary inhomogeneities

NASA Technical Reports Server (NTRS)

Daily, W. D.

1973-01-01

Pioneer 6 magnetic data reveals that the propagation direction of Alfven waves in the interplanetary medium is strongly oriented along the ambient field. Magnetic fluctuations of frequencies up to 1/30 sec in the spacecraft frame are shown to satisfy a necessary condition for Alfven wave normal. It appears from this analysis that geometrical hydromagnetics may satisfactorily describe deviation of the wave normal from the background field. The rotational discontinuity is likely also to propagate along the field lines.

Erosive Esophagitis in the Obese: The Effect of Ethnicity and Gender on Its Association.

PubMed

Abraham, Albin; Lipka, Seth; Hajar, Rabab; Krishnamachari, Bhuma; Virdi, Ravi; Jacob, Bobby; Viswanathan, Prakash; Mustacchia, Paul

2016-01-01

Background. Data examining the association between obesity and erosive esophagitis (ErE) have been inconsistent, with very little known about interracial variation. Goals. To examine the association between obesity and ErE among patients of different ethnic/racial backgrounds. Methods. The study sample included 2251 patients who underwent esophagogastroduodenoscopy (EGD). The effects of body mass index (BMI) on ErE were assessed by gender and in different ethnic groups. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression analysis. Results. The prevalence of ErE was 29.4% (661/2251). Overweight and obese subjects were significantly more likely to have ErE than individuals with a normal BMI, with the highest risk seen in the morbidly obese (OR 6.26; 95% CI 3.82-10.28; p < 0.0001). Normal weight Black patients were less likely to have ErE as compared to Caucasians (OR 0.46; 95% CI 0.27-0.79; p = 0.005), while the odds ratio comparing normal weight Hispanics to normal weight Whites was not statistically significant. No effect modification was seen between BMI and race/ethnicity or BMI and gender. Significant trends were seen in each gender and ethnicity. Conclusions. The effect of BMI on ErE does not appear to vary by race/ethnicity or gender.

Stress and the HPA Axis

PubMed Central

Stephens, Mary Ann C.; Wand, Gary

2012-01-01

Stress has long been suggested to be an important correlate of uncontrolled drinking and relapse. An important hormonal response system to stress—the hypothalamic–pituitary–adrenal (HPA) axis—may be involved in this process, particularly stress hormones known as glucocorticoids and primarily cortisol. The actions of this hormone system normally are tightly regulated to ensure that the body can respond quickly to stressful events and return to a normal state just as rapidly. The main determinants of HPA axis activity are genetic background, early-life environment, and current life stress. Alterations in HPA axis regulation are associated with problematic alcohol use and dependence; however, the nature of this dysregulation appears to vary with respect to stage of alcohol dependence. Much of this research has focused specifically on the role of cortisol in the risk for, development of, and relapse to chronic alcohol use. These studies found that cortisol can interact with the brain’s reward system, which may contribute to alcohol’s reinforcing effects. Cortisol also can influence a person’s cognitive processes, promoting habit-based learning, which may contribute to habit formation and risk of relapse. Finally, cortisol levels during abstinence may be useful clinical indicators of relapse vulnerability in alcohol-dependent people. PMID:23584113

Targeting of phage particles towards endothelial cells by antibodies selected through a multi-parameter selection strategy.

PubMed

Mandrup, Ole A; Lykkemark, Simon; Kristensen, Peter

2017-02-10

One of the hallmarks of cancer is sustained angiogenesis. Here, normal endothelial cells are activated, and their formation of new blood vessels leads to continued tumour growth. An improved patient condition is often observed when angiogenesis is prevented or normalized through targeting of these genomically stable endothelial cells. However, intracellular targets constitute a challenge in therapy, as the agents modulating these targets have to be delivered and internalized specifically to the endothelial cells. Selection of antibodies binding specifically to certain cell types is well established. It is nonetheless a challenge to ensure that the binding of antibodies to the target cell will mediate internalization. Previously selection of such antibodies has been performed targeting cancer cell lines; most often using either monovalent display or polyvalent display. In this article, we describe selections that isolate internalizing antibodies by sequential combining monovalent and polyvalent display using two types of helper phages, one which increases display valence and one which reduces background. One of the selected antibodies was found to mediate internalization into human endothelial cells, although our results confirms that the single stranded nature of the DNA packaged into phage particles may limit applications aimed at targeting nucleic acids in mammalian cells.

Use of allopurinol with low-dose 6-mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: A review of four cases and the literature

PubMed Central

Witte, Todd N; Ginsberg, Allen L

2008-01-01

BACKGROUND: At least one-third of patients with inflammatory bowel disease do not respond or are intolerant to therapy with 6-mercaptopurine (6-MP). A subgroup fails to attain optimal levels of 6-thioguanine nucleotide (6-TGN) and instead shunts to 6-methylmercaptopurine nucleotide (6-MMPN). PATIENTS AND METHODS: A retrospective chart review was conducted, and four patients are described who had been previously unable to achieve optimal 6-TGN metabolite levels until allopurinol was added to their treatment. RESULTS: All four patients achieved optimal 6-TGN levels and undetectable 6-MMPN with a mean 6-MP dose of 0.49 mg/kg. Three achieved steroid-free clinical remission. Two of those three patients had normalization of liver enzymes; one patient had baseline normal liver enzymes despite an initial 6-MMPN level of 27,369 pmol/8×108 red blood cells. Two patients experienced reversible leukopenia. CONCLUSIONS: Combination allopurinol and low-dose 6-MP is an effective means to achieve optimal metabolite levels and steroid-free clinical remission in previously refractory patients. Caution is advised. PMID:18299738

Identification of differential pathways in papillary thyroid carcinoma utilizing pathway co-expression analysis.

PubMed

Qiu, Wei-Hai; Chen, Gui-Yan; Cui, Lu; Zhang, Ting-Ming; Wei, Feng; Yang, Yong

2016-01-01

To identify differential pathways between papillary thyroid carcinoma (PTC) patients and normal controls utilizing a novel method which combined pathway with co-expression network. The proposed method included three steps. In the first step, we conducted pretreatments for background pathways and gained representative pathways in PTC. Subsequently, a co-expression network for representative pathways was constructed using empirical Bayes (EB) approach to assign a weight value for each pathway. Finally, random model was extracted to set the thresholds of identifying differential pathways. We obtained 1267 representative pathways and their weight values based on the co-expressed pathway network, and then by meeting the criterion (Weight > 0.0296), 87 differential pathways in total across PTC patients and normal controls were identified. The top three ranked differential pathways were CREB phosphorylation, attachment of GPI anchor to urokinase plasminogen activator receptor (uPAR) and loss of function of SMAD2/3 in cancer. In conclusion, we successfully identified differential pathways (such as CREB phosphorylation, attachment of GPI anchor to uPAR and post-translational modification: synthesis of GPI-anchored proteins) for PTC using the proposed pathway co-expression method, and these pathways might be potential biomarkers for target therapy and detection of PTC.

Identification of Candida albicans by using different culture medias and its association in potentially malignant and malignant lesions

PubMed Central

Saigal, Sonal; Bhargava, Ankur; Mehra, S. K.; Dakwala, Falguni

2011-01-01

Background and Objective: The present study evaluates the association of Candida albicans with normal control group, potentially malignant and malignant lesions of oral cavity by using two different liquid culture media. Materials and Methods: Saliva was collected and biopsy was taken only from those clinically suspected potentially malignant and malignant lesions for histopathological diagnosis. Saliva samples were inoculated for fungal growth in Sabouraud's dextrose agar and culture-positive samples had undergone for Germ tube test. Germ tube-positive samples were further taken for quantification of chlamydospore production in liquid media at 8 and 16 hours. Results: In normal control groups no fungus growth was found; however, potentially malignant and malignant cases showed fungus growth, positive germ tube test and chlamydospore formation. The result also showed rapid and quantitatively more chlamydospore formation in corn meal broth + 5% milk in comparison to serum milk culture media. Conclusion: The oral mucosa is compromised in potentially malignant lesions, it can be argued that this species may be involved in carcinogenesis by elaborating the nitrosamine compounds which either act directly on oral mucosa or interact with other chemical carcinogens to activate specific proto-oncogenes and thereby initiate oral neoplasia. PMID:22090762

Cardiorespiratory performance and physical activity in normal weight and overweight Finnish adolescents from 2003 to 2010.

PubMed

Palomäki, Sanna; Heikinaro-Johansson, Pilvikki; Huotari, Pertti

2015-01-01

We investigated changes in cardiorespiratory performance, BMI and leisure-time physical activity among Finnish adolescents from 2003 to 2010. In addition, we compared cardiorespiratory performance levels between normal weight and overweight adolescents, grouped according to their physical activity. Participants were a national representative samples of 15-16-year-old adolescents in their final (ninth) year of comprehensive school in 2003 (n = 2258) and in 2010 (n = 1301). They performed an endurance shuttle run test and reported their height and weight and leisure time physical activity on a questionnaire. Results showed no significant secular changes in cardiorespiratory performance from 2003 to 2010. The mean BMI increased in boys. Leisure-time physical activity increased among normal weight girls. Adolescents of normal weight had better cardiorespiratory performance than those classified as overweight at both assessment points. BMI-adjusted physical activity was a significant determinant for cardiorespiratory performance among overweight adolescents, and very active overweight adolescents had similar cardiorespiratory performance levels as moderately active adolescents of normal weight. The results of the present study support the idea that the physical activity has the great importance for the cardiorespiratory performance in adolescents. Overweight adolescents, in particular, benefit from higher levels of physical activity.

Abnormalities in the cellular phase of blood fibrinolytic activity in systemic lupus erythematosus and in venous thromboembolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moroz, L.A.; MacLean, L.D.; Langleben, D.

1986-09-15

Fibrinolytic activities of whole blood and plasma were determined by /sup 125/I-fibrin radiometric assay in 16 normal subjects, and in 11 patients with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 23 with venous thromboembolic disease, and 20 patients awaiting elective surgery. Mean whole blood and plasma activities for patients with PSS, and for those awaiting elective surgery, were similar to normal values, as was the mean plasma activity in patients with SLE. However, mean whole blood activity in SLE was significantly decreased compared with normals (p less than 0.05), with mean plasma activity accounting for 44% ofmore » mean whole blood activity (compared with 17% in normal subjects), representing a 67% decrease in mean calculated cellular phase activity in SLE, when compared with normals. Since the numbers of cells (neutrophils, monocytes) possibly involved in cellular activity were not decreased, the findings suggest a functional defect in fibrinolytic activity of one or more blood cell types in SLE. An additional finding was the participation of the cellular phase as well as the well-known plasma phase of blood in the fibrinolytic response to thromboembolism.« less

76 FR 30969 - Importer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-27

... treatment of wounds which contain trace amounts of the controlled substances normally found in poppy straw... company's background and history. Therefore, pursuant to 21 U.S.C. 952(a) and 958(a), and in accordance...

Industrial Microorganisms.

ERIC Educational Resources Information Center

Phaff, Herman J.

1981-01-01

Describes industrially important yeasts, molds, bacteria, and actinomycetes. Discussed in detail are microbial products, such as primary metabolites, secondary metabolites, enzymes, and capsular polysaccharides. Traces the historical background of human cell culture, mentioning recombinant DNA research and hybridization of normal mammalian cells…

Engineering epithelial-stromal interactions in vitro for toxicology assessment

EPA Science Inventory

Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo t...

The aeromedical significance of sickle-cell trait : a review.

DOT National Transportation Integrated Search

1976-01-01

This report present some of the technical background necessary for understanding the aeromedical importance of sickle-cell disease and the sickle-trait carrier, whose erythrocytes contain mixtures of hemoglobin S and normal hemoglobin A. This carrier...

A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas

PubMed Central

Radovich, Milan; Solzak, Jeffrey P; Hancock, Bradley A; Conces, Madison L; Atale, Rutuja; Porter, Ryan F; Zhu, Jin; Glasscock, Jarret; Kesler, Kenneth A; Badve, Sunil S; Schneider, Bryan P; Loehrer, Patrick J

2016-01-01

Background: Thymomas are one of the most rarely diagnosed malignancies. To better understand its biology and to identify therapeutic targets, we performed next-generation RNA sequencing. Methods: The RNA was sequenced from 13 thymic malignancies and 3 normal thymus glands. Validation of microRNA expression was performed on a separate set of 35 thymic malignancies. For cell-based studies, a thymoma cell line was used. Results: Hierarchical clustering revealed 100% concordance between gene expression clusters and WHO subtype. A substantial differentiator was a large microRNA cluster on chr19q13.42 that was significantly overexpressed in all A and AB tumours and whose expression was virtually absent in the other thymomas and normal tissues. Overexpression of this microRNA cluster activates the PI3K/AKT/mTOR pathway. Treatment of a thymoma AB cell line with a panel of PI3K/AKT/mTOR inhibitors resulted in marked reduction of cell viability. Conclusions: A large microRNA cluster on chr19q13.42 is a transcriptional hallmark of type A and AB thymomas. Furthermore, this cluster activates the PI3K pathway, suggesting the possible exploration of PI3K inhibitors in patients with these subtypes of tumour. This work has led to the initiation of a phase II clinical trial of PI3K inhibition in relapsed or refractory thymomas (http://clinicaltrials.gov/ct2/show/NCT02220855). PMID:26766736

Elastic intramedullary nailing and DBM-Bone marrow injection for the treatment of simple bone cysts

PubMed Central

Kanellopoulos, Anastasios D; Mavrogenis, Andreas F; Papagelopoulos, Panayiotis J; Soucacos, Panayotis N

2007-01-01

Background Simple or unicameral bone cysts are common benign fluid-filled lesions usually located at the long bones of children before skeletal maturity. Methods We performed demineralized bone matrix and iliac crest bone marrow injection combined with elastic intramedullary nailing for the treatment of simple bone cysts in long bones of 9 children with a mean age of 12.6 years (range, 4 to 15 years). Results Two of the 9 patients presented with a pathological fracture. Three patients had been referred after the failure of previous treatments. Four patients had large lesions with impending pathological fractures that interfered with daily living activities. We employed a ratio to ascertain the severity of the lesion. The extent of the lesion on the longitudinal axis was divided with the normal expected diameter of the long bone at the site of the lesion. The mean follow-up was 77 months (range, 5 to 8 years). All patients were pain free and had full range of motion of the adjacent joints at 6 weeks postoperatively. Review radiographs showed that all 7 cysts had consolidated completely (Neer stage I) and 2 cysts had consolidated partially (Neer stage II). Until the latest examination there was no evidence of fracture or re-fracture. Conclusion Elastic intramedullary nailing has the twofold benefits of continuous cyst decompression, and early immediate stability to the involved bone segment, which permits early mobilization and return to the normal activities of the pre-teen patients. PMID:17916249

Influence of Blood Lipids on Global Coagulation Test Results

PubMed Central

Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon

2015-01-01

Background High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). Methods PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). Results The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. Conclusion High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels. PMID:25553275

Human H-reflexes are smaller in difficult beam walking than in normal treadmill walking.

PubMed

Llewellyn, M; Yang, J F; Prochazka, A

1990-01-01

Hoffman (H) reflexes were elicited from the soleus (SOL) muscle while subjects walked on a treadmill and on a narrow beam (3.5 cm wide, raised 34 cm from the floor). The speed of walking on the treadmill was selected for each subject to match the background activation level of their SOL muscle during beam walking. The normal reciprocal activation pattern of the tibialis anterior and SOL muscles in treadmill walking was replaced by a pattern dominated by co-contraction on the beam. In addition, the step cycle duration was more variable and the time spent in the swing phase was reduced on the beam. The H-reflexes were highly modulated in both tasks, the amplitude being high in the stance phase and low in the swing phase. The H-reflex amplitude was on average 40% lower during beam walking than treadmill walking. The relationship between the H-reflex amplitude and the SOL EMG level was quantified by a regression line relating the two variables. The slope of this line was on average 41% lower in beam walking than treadmill walking. The lower H-reflex gain observed in this study and the high level of fusimotor drive observed in cats performing similar tasks suggest that the two mechanisms which control the excitability of this reflex pathway (i.e. fusimotor action and control of transmission at the muscle spindle to moto-neuron synapse) may be controlled independently.

A WUSCHEL-Independent Stem Cell Specification Pathway Is Repressed by PHB, PHV and CNA in Arabidopsis.

PubMed

Lee, Chunghee; Clark, Steven E

2015-01-01

The homeostatic maintenance of stem cells that carry out continuous organogenesis at the shoot meristem is crucial for plant development. Key known factors act to signal between the stem cells and an underlying group of cells thought to act as the stem cell niche. In Arabidopsis thaliana the homeodomain transcription factor WUSCHEL (WUS) is essential for stem cell initiation and maintenance at shoot and flower meristems. Recent data suggest that the WUS protein may move from the niche cells directly into the stem cells to maintain stem cell identity. Here we provide evidence for a second, previously unknown, pathway for stem cell specification at shoot and flower meristems that bypasses the requirement for WUS. We demonstrate that this novel stem cell specification pathway is normally repressed by the activity of the HD-zip III transcription factors PHABULOSA (PHB), PHAVOLUTA (PHV) and CORONA (CNA). When de-repressed, this second stem cell pathway leads to an accumulation of stem cells and an enlargement of the stem cell niche. When de-repressed in a wus mutant background, this second stem cell pathway leads to functional meristems with largely normal cell layering and meristem morphology, activation of WUS cis regulatory elements, and extensive, but not indeterminate, organogenesis. Thus, WUS is largely dispensable for stem cell specification and meristem function, suggesting a set of key stem cell specification factors, competitively regulated by WUS and PHB/PHV/CNA, remain unidentified.

A WUSCHEL-Independent Stem Cell Specification Pathway Is Repressed by PHB, PHV and CNA in Arabidopsis

PubMed Central

Lee, Chunghee; Clark, Steven E.

2015-01-01

The homeostatic maintenance of stem cells that carry out continuous organogenesis at the shoot meristem is crucial for plant development. Key known factors act to signal between the stem cells and an underlying group of cells thought to act as the stem cell niche. In Arabidopsis thaliana the homeodomain transcription factor WUSCHEL (WUS) is essential for stem cell initiation and maintenance at shoot and flower meristems. Recent data suggest that the WUS protein may move from the niche cells directly into the stem cells to maintain stem cell identity. Here we provide evidence for a second, previously unknown, pathway for stem cell specification at shoot and flower meristems that bypasses the requirement for WUS. We demonstrate that this novel stem cell specification pathway is normally repressed by the activity of the HD-zip III transcription factors PHABULOSA (PHB), PHAVOLUTA (PHV) and CORONA (CNA). When de-repressed, this second stem cell pathway leads to an accumulation of stem cells and an enlargement of the stem cell niche. When de-repressed in a wus mutant background, this second stem cell pathway leads to functional meristems with largely normal cell layering and meristem morphology, activation of WUS cis regulatory elements, and extensive, but not indeterminate, organogenesis. Thus, WUS is largely dispensable for stem cell specification and meristem function, suggesting a set of key stem cell specification factors, competitively regulated by WUS and PHB/PHV/CNA, remain unidentified. PMID:26011610

A Soxhlet Extract of Gongronema latifolium Retains Moderate Blood Glucose Lowering Effect and Produces Structural Recovery in the Pancreas of STZ-Induced Diabetic Rats

PubMed Central

Al-Hindi, Bassel; Yusoff, Nor A.; Atangwho, Item J.; Ahmad, Mariam; Asmawi, Mohd Z.; Yam, Mun F.

2016-01-01

Background: Gongronema latifolium Benth. (GL) possesses considerable glucose lowering effects able to be utilized on a large-scale. This paper investigates the effects of a Soxhlet extract on hyperglycemia, Langerhans islets and glucose uptake by abdominal muscles. Methods: Ethanol and a Soxhlet apparatus were used to obtain GL ethanolic Soxhlet extract (GLES). It was then administered to randomly-segregated male Sprague-Dawley, normal and STZ-induced diabetic rats, using oral gavage to evaluate blood glucose levels (BGLs), serum lipid profile, insulin levels and the pancreas post-treatment. Results: GLES significantly (p < 0.05) decreased BGLs of normal rats in glucose tolerance testing at a dose of 2 g/kg b.w. but failed to do so in diabetic rats undergoing acute 7-h treatment. Given twice-daily, 1 g/kg b.w. of GLES moderately controlled diabetic BGLs starting from day 10. After 14 days of treatment, 1 g/kg and 0.5 g/kg b.w. of GLES caused 44% and 50% respective increases in the average area of Langerhans islets compared to DC. Using isolated rat abdominal muscle, GLES was found to be a mild insulin-sensitizer. GC-MS analysis revealed the presence of the known glucose-lowering phytosterol, Sitostenone. Conclusion: Despite retaining moderate antidiabetic activity, Soxhlet extraction of Gongronema latifolium probably leads to the destruction of active heat-liable compounds. PMID:29083373

Background norepinephrine primes astrocytic calcium responses to subsequent norepinephrine stimuli in the cerebral cortex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nuriya, Mutsuo; Keio Advanced Research Center for Water Biology and Medicine, Keio University, Shinjuku, Tokyo, 160-8582; Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, Kanagawa, 240-8501

Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This primingmore » effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex. - Highlights: • Background NE augments the responsiveness of astrocytes to subsequent NE stimulation. • The priming effect is independent of neuronal activity and mediated by βadrenoceptor. • Background subthreshold NE may play gliomodulatory roles in the cerebral cortex.« less

Differential regulation of cell functions by CSD peptide subdomains

PubMed Central

2013-01-01

Background In fibrotic lung diseases, expression of caveolin-1 is decreased in fibroblasts and monocytes. The effects of this deficiency are reversed by treating cells or animals with the caveolin-1 scaffolding domain peptide (CSD, amino acids 82–101 of caveolin-1) which compensates for the lack of caveolin-1. Here we compare the function of CSD subdomains (Cav-A, Cav-B, Cav-C, Cav-AB, and Cav-BC) and mutated versions of CSD (F92A and T90A/T91A/F92A). Methods Migration toward the chemokine CXCL12 and the associated expression of F-actin, CXCR4, and pSmad 2/3 were studied in monocytes from healthy donors and SSc patients. Fibrocyte differentiation was studied using PBMC from healthy donors and SSc patients. Collagen I secretion and signaling were studied in fibroblasts derived from the lung tissue of healthy subjects and SSc patients. Results Cav-BC and CSD at concentrations as low as 0.01 μM inhibited the hypermigration of SSc monocytes and TGFβ-activated Normal monocytes and the differentiation into fibrocytes of SSc and Normal monocytes. While CSD also inhibited the migration of poorly migrating Normal monocytes, Cav-A (and other subdomains to a lesser extent) promoted the migration of Normal monocytes while inhibiting the hypermigration of TGFβ-activated Normal monocytes. The effects of versions of CSD on migration may be mediated in part via their effects on CXCR4, F-actin, and pSmad 2/3 expression. Cav-BC was as effective as CSD in inhibiting fibroblast collagen I and ASMA expression and MEK/ERK signaling. Cav-C and Cav-AB also inhibited collagen I expression, but in many cases did not affect ASMA or MEK/ERK. Cav-A increased collagen I expression in scleroderma lung fibroblasts. Full effects on fibroblasts of versions of CSD required 5 μM peptide. Conclusions Cav-BC retains most of the anti-fibrotic functions of CSD; Cav-A exhibits certain pro-fibrotic functions. Results obtained with subdomains and mutated versions of CSD further suggest that the critical functional residues in CSD depend on the cell type and readout being studied. Monocytes may be more sensitive to versions of CSD than fibroblasts and endothelial cells because the baseline level of caveolin-1 in monocytes is much lower than in these other cell types. PMID:24011378

Generation of Rising-tone Chorus in a Two-dimensional Mirror Field by Using the General Curvilinear PIC Code

NASA Astrophysics Data System (ADS)

Ke, Y.; Gao, X.; Lu, Q.; Wang, X.; Wang, S.

2017-12-01

Recently, the generation of rising-tone chorus has been implemented with one-dimensional (1-D) particle-in-cell (PIC) simulations in an inhomogeneous background magnetic field, where both the propagation of waves and motion of electrons are simply forced to be parallel to the background magnetic field. We have developed a two-dimensional(2-D) general curvilinear PIC simulation code, and successfully reproduced rising-tone chorus waves excited from an anisotropic electron distribution in a 2-D mirror field. Our simulation results show that whistler waves are mainly generated around the magnetic equator, and continuously gain growth during their propagation toward higher-latitude regions. The rising-tone chorus waves are formed off the magnetic equator, which propagate quasi-parallel to the background magnetic field with the finite wave normal angle. Due to the propagating effect, the wave normal angle of chorus waves is increasing during their propagation toward higher-latitude regions along an enough curved field line. The chirping rate of chorus waves are found to be larger along a field line more close to the middle field line in the mirror field.

Generation of rising-tone chorus in a two-dimensional mirror field by using the general curvilinear PIC code

NASA Astrophysics Data System (ADS)

Ke, Yangguang; Gao, Xinliang; Lu, Quanming; Wang, Xueyi; Wang, Shui

2017-08-01

Recently, the generation of rising-tone chorus has been implemented with one-dimensional (1-D) particle-in-cell (PIC) simulations in an inhomogeneous background magnetic field, where both the propagation of waves and motion of electrons are simply forced to be parallel to the background magnetic field. In this paper, we have developed a two-dimensional (2-D) general curvilinear PIC simulation code and successfully reproduced rising-tone chorus waves excited from an anisotropic electron distribution in a 2-D mirror field. Our simulation results show that whistler waves are mainly generated around the magnetic equator and continuously gain growth during their propagation toward higher-latitude regions. The rising-tone chorus waves are observed off the magnetic equator, which propagate quasi-parallel to the background magnetic field with the wave normal angle smaller than 25°. Due to the propagating effect, the wave normal angle of chorus waves is increasing during their propagation toward higher-latitude regions along an enough curved field line. The chirping rate of chorus waves is found to be larger along a field line with a smaller curvature.

The effect of voice quality and competing speakers in a passage comprehension task: performance in relation to cognitive functioning in children with normal hearing.

PubMed

von Lochow, Heike; Lyberg-Åhlander, Viveka; Sahlén, Birgitta; Kastberg, Tobias; Brännström, K Jonas

2018-04-01

This study explores the effect of voice quality and competing speaker/-s on children's performance in a passage comprehension task. Furthermore, it explores the interaction between passage comprehension and cognitive functioning. Forty-nine children (27 girls and 22 boys) with normal hearing (aged 7-12 years) participated. Passage comprehension was tested in six different listening conditions; a typical voice (non-dysphonic voice) in quiet, a typical voice with one competing speaker, a typical voice with four competing speakers, a dysphonic voice in quiet, a dysphonic voice with one competing speaker, and a dysphonic voice with four competing speakers. The children's working memory capacity and executive functioning were also assessed. The findings indicate no direct effect of voice quality on the children's performance, but a significant effect of background listening condition. Interaction effects were seen between voice quality, background listening condition, and executive functioning. The children's susceptibility to the effect of the dysphonic voice and the background listening conditions are related to the individual's executive functions. The findings have several implications for design of interventions in language learning environments such as classrooms.

The intestinal absorption of dietary cholesterol by hypercholesterolemic (type II) and normocholesterolemic humans.

PubMed

Connor, W E; Lin, D S

1974-04-01

The incomplete absorption of dietary cholesterol may represent an adaptive intestinal barrier that prevents hypercholesterolemia. To explore this mechanism, we compared cholesterol absorption in 15 normocholesterolemic and 6 hypercholesterolemic (type II) subjects fed background cholesterol-free formula diets with 40% of calories as fat. Each test meal consisted of a breakfast into which was incorporated scrambled egg yolk containing 300-500 mg of cholesterol and [4-(14)C]cholesterol (3-22 muCi), either naturally incorporated into the yolk cholesterol by previous isotope injection into the laying hen or added in peanut oil to the yolk of the test breakfast. In some instances [1alpha-(3)H]cholesterol was the radioactive marker. The radioactivity of the fecal neutral sterol fraction was determined in daily stool samples for the next 7 days to provide an estimate of unabsorbed dietary cholesterol. The amount of absorbed and reexcreted labeled cholesterol proved negligible. Most unabsorbed dietary cholesterol appeared in the stool on the second or third day after the meal, and 95% or more was recovered in the stool by 6 days. Plasma specific activity curves were usually maximal at 48 h. Normal subjects absorbed 44.5+/-9.3 (SD) of the administered cholesterol (range 25.9-60.3). Hypercholesterolemics absorbed the same percentage of cholesterol as normals: 47.6+/-12.6% (range 29.3-67.3). Absorption was similar whether the radiolabeled cholesterol was added to egg yolk or naturally incorporated in it (42.1+/-9.3 vs. 48.9+/-9.8%). Six normal subjects were fed a cholesterol-free formula for 4 wk, and then different amounts of cholesterol (110-610 mg/day) were added for another 4 wk. At the end of each period, single test meals containing either 110, 310, or 610 mg of cholesterol and [1alpha-(3)H]cholesterol were administered. Cholesterol absorption was 42.3+/-6.0% and 45.4+/-8.3% for the two dietary periods, respectively. The absolute cholesterol absorption was linearly related to the amount of cholesterol in the test meal, and absorption was not affected by background diets high or low in cholesterol content.

Fibroblast Activation Protein (FAP) Is Essential for the Migration of Bone Marrow Mesenchymal Stem Cells through RhoA Activation

PubMed Central

Chung, Kuei-Min; Hsu, Shu-Ching; Chu, Yue-Ru; Lin, Mei-Yao; Jiaang, Weir-Tong; Chen, Ruey-Hwa; Chen, Xin

2014-01-01

Background The ability of human bone marrow mesenchymal stem cells (BM-MSCs) to migrate and localize specifically to injured tissues is central in developing therapeutic strategies for tissue repair and regeneration. Fibroblast activation protein (FAP) is a cell surface serine protease expressed at sites of tissue remodeling during embryonic development. It is also expressed in BM-MSCs, but not in normal tissues or cells. The function of FAP in BM-MSCs is not known. Principal Findings We found that depletion of FAP proteins significantly inhibited the migration of BM-MSCs in a transwell chemotaxis assay. Such impaired migration ability of BM-MSCs could be rescued by re-expressing FAP in these cells. We then demonstrated that depletion of FAP activated intracellular RhoA GTPase. Consistently, inhibition of RhoA activity using a RhoA inhibitor rescued its migration ability. Inhibition of FAP activity with an FAP-specific inhibitor did not affect the activation of RhoA or the migration of BM-MSCs. Furthermore, the inflammatory cytokines interleukin-1beta (IL-1β) and transforming growth factor-beta (TGF-β) upregulated FAP expression, which coincided with better BM-MSC migration. Conclusions Our results indicate FAP plays an important role in the migration of BM-MSCs through modulation of RhoA GTPase activity. The peptidase activity of FAP is not essential for such migration. Cytokines IL-1β and TGF-β upregulate the expression level of FAP and thus enhance BM-MSC migration. PMID:24551161

Prevalence and socio-demographic correlates of the compliance with the physical activity guidelines in children and adolescents in Germany.

PubMed

Jekauc, Darko; Reimers, Anne K; Wagner, Matthias O; Woll, Alexander

2012-08-30

Regular physical activity (PA) is a prerequisite for normal growth and maturation, health, and fitness of children and adolescents. Because of the growing evidence of the health benefits of regular PA, several national and international public health organisations have established PA guidelines. The purpose of this study was to assess the percentage of children and adolescents in Germany who meet the PA guideline of 60 minutes of moderate-to-vigorous PA each day and to evaluate socio-demographic correlates of compliance with the PA guideline. The sample consists of 4,529 children and adolescents aged between 4 and 17 years who lived and were registered in the Federal Republic of Germany between 2003 and 2006. The compliance with the PA guideline was assessed using a widely accepted screening measure. Socioeconomic status, immigration background and residential area were assessed using a parent questionnaire. Overall, 13.1% of girls and 17.4% of boys complied with the national guideline of 60 minutes of moderate-to-vigorous PA daily. While compliance was significantly lower in older participants of both gender groups, the steepest decrease in compliance was observed for age groups around the transition time from primary to secondary school. Logistic regression revealed that socioeconomic status and a migration background were significant predictors for compliance in girls and residential area for compliance in boys. Programs and policy action addressing the problem of decreasing compliance with PA guideline with increasing age are warranted. The transition from primary school to secondary school seems to be a critical stage in life with respect to PA behaviour. Therefore, specific interventions should aim at restructuring and reorganising their daily and physical activities during this transition.

Physical activity during pregnancy in obese and normal-weight women as assessed by pedometer.

PubMed

Renault, Kristina; Nørgaard, Kirsten; Andreasen, Kirsten Riis; Secher, Niels Jørgen; Nilas, Lisbeth

2010-07-01

To compare physical activity as assessed by a pedometer in obese and normal-weight pregnant women at different gestational ages. To evaluate the use of a pedometer in pregnancy. Cross-sectional study. Department of obstetrics and gynecology in a university hospital in Copenhagen. 338 pregnant women, 175 normal-weight women with body mass index (BMI) 20-25 kg/m(2) and 163 obese women with BMI > or = 30 kg/m(2). Physical activity was assessed by a pedometer (Yamax Digiwalker SW-700/701) on seven consecutive days in six different groups: normal-weight or obese at gestational ages 11-13, 18-22, and 36-38, and expressed as median number of daily steps during a whole week, working days, and weekends. Relation between BMI and physical activity during pregnancy and compliance with wearing the pedometer. Noncompliance was more frequent in obese than in normal-weight women (19 vs. 10%, p < 0.001). Physical activity was lower in obese women at all gestational ages (6,482, 7,446, 4,626 steps/day in obese vs. 7,558, 8,865, 6,289 steps/day in normal-weight, p < 0.05-0.11). The greatest difference between obese and normal-weight women was seen during weekends. The level of physical activity was higher in both groups at mid-gestation than during earlier and later gestational ages. Physical activity in pregnant women can be assessed by the pedometer and the method was well accepted by the women; however, the compliance was lower in the obese. The level of physical activity differs between different gestational groups and is lower in obese than in normal-weight women, especially during leisure time.

Comparison of CyTOF assays across sites: Results of a six-center pilot study.

PubMed

Leipold, Michael D; Obermoser, Gerlinde; Fenwick, Craig; Kleinstuber, Katja; Rashidi, Narges; McNevin, John P; Nau, Allison N; Wagar, Lisa E; Rozot, Virginie; Davis, Mark M; DeRosa, Stephen; Pantaleo, Giuseppe; Scriba, Thomas J; Walker, Bruce D; Olsen, Lars R; Maecker, Holden T

2018-02-01

For more than five years, high-dimensional mass cytometry has been employed to study immunology. However, these studies have typically been performed in one laboratory on one or few instruments. We present the results of a six-center study using healthy control human peripheral blood mononuclear cells (PBMCs) and commercially available reagents to test the intra-site and inter-site variation of mass cytometers and operators. We used prestained controls generated by the primary center as a reference to compare against samples stained at each individual center. Data were analyzed at the primary center, including investigating the effects of two normalization methods. All six sites performed similarly, with CVs for both Frequency of Parent and median signal intensity (MSI) values<30%. Increased background was seen when using the premixed antibody cocktail aliquots at each site, suggesting that cocktails are best made fresh. Both normalization methods tested performed adequately for normalizing MSI values between centers. Clustering algorithms revealed slight differences between the prestained and the sites-stained samples, due mostly to the increased background of a few antibodies. Therefore, we believe that multicenter mass cytometry assays are feasible. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Effects of normalization on quantitative traits in association test

PubMed Central

2009-01-01

Background Quantitative trait loci analysis assumes that the trait is normally distributed. In reality, this is often not observed and one strategy is to transform the trait. However, it is not clear how much normality is required and which transformation works best in association studies. Results We performed simulations on four types of common quantitative traits to evaluate the effects of normalization using the logarithm, Box-Cox, and rank-based transformations. The impact of sample size and genetic effects on normalization is also investigated. Our results show that rank-based transformation gives generally the best and consistent performance in identifying the causal polymorphism and ranking it highly in association tests, with a slight increase in false positive rate. Conclusion For small sample size or genetic effects, the improvement in sensitivity for rank transformation outweighs the slight increase in false positive rate. However, for large sample size and genetic effects, normalization may not be necessary since the increase in sensitivity is relatively modest. PMID:20003414

The D153del Mutation in GNB3 Gene Causes Tissue Specific Signalling Patterns and an Abnormal Renal Morphology in Rge Chickens

PubMed Central

Tummala, Hemanth; Fleming, Stewart; Hocking, Paul M.; Wehner, Daniel; Naseem, Zahid; Ali, Manir; Inglehearn, Christopher F.; Zhelev, Nikolai; Lester, Douglas H.

2011-01-01

Background The GNB3 gene is expressed in cone but not rod photoreceptors of vertebrates, where it acts as the β transducin subunit in the colour visual transduction process. A naturally occurring mutation ‘D153del’ in the GNB3 gene causes the recessively inherited blinding phenotype retinopathy globe enlarged (rge) disease in chickens. GNB3 is however also expressed in most other vertebrate tissues suggesting that the D153del mutation may exert pathological effects that outlie from eye. Principal Findings Recombinant studies in COS-7 cells that were transfected with normal and mutant recombinant GNB3 constructs and subjected to cycloheximide chase showed that the mutant GNB3d protein had a much shorter half life compared to normal GNB3. GNB3 codes for the Gβ3 protein subunit that, together with different Gγ and Gα subunits, activates and regulates phosphorylation cascades in different tissues. As expected, the relative levels of cGMP and cAMP secondary messengers and their activated kinases such as MAPK, AKT and GRK2 were also found to be altered significantly in a tissue specific manner in rge chickens. Histochemical analysis on kidney tissue sections, from rge homozygous affected chickens, showed the chickens had enlargement of the glomerular capsule, causing glomerulomegaly and tubulointerstitial inflammation whereas other tissues (brain, heart, liver, pancreas) were unaffected. Significance These findings confirm that the D153del mutation in GNB3 gene targets GNB3 protein to early degradation. Lack of GNB3 signalling causes reduced phosphorylation activity of ERK2 and AKT leading to severe pathological phenotypes such as blindness and renal abnormalities in rge chickens. PMID:21887213

Complete regression of human malignant mesothelioma xenografts following local injection of midkine promoter-driven oncolytic adenovirus

PubMed Central

Kubo, Shuji; Kawasaki, Yoshiko; Yamaoka, Norie; Tagawa, Masatoshi; Kasahara, Noriyuki; Terada, Nobuyuki; Okamura, Haruki

2010-01-01

Background Malignant mesothelioma is a highly aggressive tumor with poor prognosis. Conventional therapies for mesothelioma are generally non-curative, and new treatment paradigms are urgently needed. We hypothesized that the tumor-specific midkine (Mdk) promoter could confer transcriptional targeting to oncolytic adenoviruses for effective treatment of malignant mesothelioma. Methods We analyzed Mdk expression by quantitative RT-PCR in six human mesothelioma cell lines, and tested Mdk promoter activity by luciferase reporter assay. Based on these data, we constructed a replication-selective oncolytic adenovirus, designated AdMdk-E1-iresTK, which contains an Mdk promoter-driven adenoviral E1 gene and HSV-thymidine kinase (TK) suicide gene, and CMV promoter-driven green fluorescent protein (GFP) marker gene. Selectivity of viral replication and cytolysis were characterized in normal vs. mesothelioma cells in vitro, and intratumoral spread and antitumor efficacy were investigated in vivo. Results Mdk promoter activity was restricted in normal cells, but highly activated in mesothelioma cell lines. AdMdk-E1-iresTK was seen to efficiently replicate, produce viral progeny, and spread in multiple mesothelioma cell lines. Lytic spread of AdMdk-E1-iresTK mediated efficient killing of these mesothelioma cells, and its in vitro cytocidal effect was significantly enhanced by treatment with the prodrug, ganciclovir. Intratumoral injection of AdMdk-E1-iresTK caused complete regression of MESO4 and MSTO human mesothelioma xenografts in athymic mice. In vivo fluorescence imaging demonstrated intratumoral spread of AdMdk-E1-iresTK-derived signals, which vanished after tumor eradication. Conclusions These data indicate that transcriptional targeting of viral replication by the Mdk promoter represents a promising general strategy for oncolytic virotherapy of cancers with upregulated Mdk expression, including malignant mesothelioma. PMID:20635326

Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation

PubMed Central

Lee, Jong-Ho; Kim, Jin Young

2014-01-01

Background This study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF) during adolescence on the adverse behavioral outcome of neonatal maternal separation. Methods Male Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS) or left undisturbed (nonhandled, NH). Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF). Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay. Results Daily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only) compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it. Conclusion Prolonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA) axis. PMID:25031890

A Systematic Review of Electromyography Studies in Normal Shoulders to Inform Postoperative Rehabilitation Following Rotator Cuff Repair.

PubMed

Edwards, Peter K; Ebert, Jay R; Littlewood, Chris; Ackland, Tim; Wang, Allan

2017-12-01

Study Design Systematic review. Background Electromyography (EMG) has previously been used to guide postoperative rehabilitation progression following rotator cuff repair to prevent deleterious loading of early surgical repair. Objective To review the current literature investigating EMG during rehabilitation exercises in normal shoulders, and to identify exercises that meet a cut point of 15% maximal voluntary isometric contraction (MVIC) or less and are unlikely to result in excessive loading in the early postoperative stages. Methods An electronic search of MEDLINE via Ovid, Embase, CINAHL, SPORTDiscus, PubMed, and the Cochrane Library for all years up to June 2016 was performed. Studies were selected in relation to predefined selection criteria. Pooled mean MVICs were reported and classified as low (0%-15% MVIC), low to moderate (16%-20% MVIC), moderate (21%-40% MVIC), high (41%-60% MVIC), and very high (greater than 60% MVIC). Results A search identified 2159 studies. After applying the selection criteria, 20 studies were included for quality assessment, data extraction, and data synthesis. In total, 43 exercises spanning passive range of motion, active-assisted range of motion, and strengthening exercises were evaluated. Out of 13 active-assisted exercises, 9 were identified as suitable (15% MVIC or less) to load the supraspinatus and 10 as suitable to load the infraspinatus early after surgery. All exercises were placed in a theoretical-continuum model, by which general recommendations could be made for prescription in patients post rotator cuff repair. Conclusion This review identified passive and active-assisted exercises that may be appropriate in the early stages after rotator cuff repair. J Orthop Sports Phys Ther 2017;47(12):931-944. Epub 13 Jul 2017. doi:10.2519/jospt.2017.7271.

Regulation of Deoxycholate Induction of CXCL8 by the Adenomatous Polyposis Coli Gene in Colorectal Cancer

PubMed Central

Rial, Nathaniel S; Lazennec, Gwendal; Prasad, Anil R; Krouse, Robert S; Lance, Peter; Gerner, Eugene W

2009-01-01

Elevated deoxycholic acid (DCA), mutations in the adenomatous polyposis coli (APC) gene and chronic inflammation are associated with increased risk of colorectal cancer (CRC). APC status was manipulated to determine whether DCA mediates inflammatory molecules in normal or initiated colonic mucosa. DCA increased steady state mRNA and protein levels of CXCL8 in cells which do not express wild type APC. Steady state CXCL8 mRNA and protein were suppressed when cells with conditional expression of wild type APC were exposed to DCA. Immunostaining did not detect CXCL8 in normal human colonic mucosa. CXCL8 was expressed in adenomatous polyps and adenocarcinomas. CXCL8 expression correlated with nuclear β-catenin localization in epithelial cells of adenomas, but was associated with endothelial cells and neutrophils in the adenocarcinomas. DCA-mediated CXCL8 promoter-reporter activity was elevated in a mutant APC background. Wild type APC suppressed this effect. Mutation of activator protein-1 (AP-1) or nuclear factor kappa B (NF-κB) sites suppressed the activation of the CXCL8 promoter-reporter by DCA. Chromatin immunoprecipitation (ChIP) revealed that AP-1 and NF-κB binding to the 5′-promoter of CXCL8 was induced by DCA. The β-catenin transcription factor was bound to the 5′-promoter of CXCL8 in the absence or presence of DCA. Phenotypic assays determined that DCA-mediated invasion was blocked by antibody directed against CXCL8 or wild type-APC. CXCL8 exposure lead to matrix metalloproteinase-2 (MMP-2) production and increased invasion on laminin coated filters. These data suggest that DCA-mediated CXCL8 occurs in initiated colonic epithelium and neutralizing CXCL8 could reduce the invasive potential of tumors. PMID:19173296

Retinoid Signaling in Pancreatic Cancer, Injury and Regeneration

PubMed Central

Colvin, Emily K.; Susanto, Johana M.; Kench, James G.; Ong, Vivienna N.; Mawson, Amanda; Pinese, Mark; Chang, David K.; Rooman, Ilse; O'Toole, Sandra A.; Segara, Davendra; Musgrove, Elizabeth A.; Sutherland, Robert L.; Apte, Minoti V.; Scarlett, Christopher J.; Biankin, Andrew V.

2011-01-01

Background Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC). These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC. Methodology/Principal Findings We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1), a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A). However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies. Conclusions/Significance In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1. PMID:22220202

Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs

PubMed Central

Butt, Adeel Masood; Mohd Amin, Mohd Cairul Iqbal; Katas, Haliza

2015-01-01

Background Doxorubicin (DOX), an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407) and vitamin E TPGS (D-α-tocopheryl polyethylene glycol succinate, TPGS) are widely used polymers as drug delivery carriers and excipients for enhancing the drug retention times and stability. TPGS reduces multidrug resistance, induces apoptosis, and shows selective anticancer activity against tumor cells. Keeping in view the problems, we designed a mixed micelle system encapsulating DOX comprising TPGS for its selective anticancer activity and P407 conjugated with folic acid (FA) for folate-mediated receptor targeting to cancer cells. Methods FA-functionalized P407 was prepared by carbodiimide crosslinker chemistry. P407-TPGS/FA-P407-TPGS-mixed micelles were prepared by thin-film hydration method. Cytotoxicity of blank micelles, DOX, and DOX-loaded micelles was determined by alamarBlue® assay. Results The size of micelles was less than 200 nm with encapsulation efficiency of 85% and 73% for P407-TPGS and FA-P407-TPGS micelles, respectively. Intracellular trafficking study using nile red-loaded micelles indicated improved drug uptake and perinuclear drug localization. The micelles show minimal toxicity to normal human cell line WRL-68, enhanced cellular uptake of DOX, reduced drug efflux, increased DOX–DNA binding in SKOV3 and DOX-resistant SKOV3 human ovarian carcinoma cell lines, and enhanced in vitro cytotoxicity as compared to free DOX. Conclusion FA-P407-TPGS-DOX micelles show potential as a targeted nano-drug delivery system for DOX due to their multiple synergistic factors of selective anticancer activity, inhibition of multidrug resistance, and folate-mediated selective uptake. PMID:25709451

Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy

PubMed Central

2013-01-01

Background Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. Methods CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Results Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. Conclusions After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation. PMID:23664008

Excessive Vitamin E Intake Does Not Cause Bone Loss in Male or Ovariectomized Female Mice Fed Normal or High-Fat Diets.

PubMed

Ikegami, Hiroko; Kawawa, Rie; Ichi, Ikuyo; Ishikawa, Tomoko; Koike, Taisuke; Aoki, Yoshinori; Fujiwara, Yoko

2017-10-01

Background: Animal studies on the effects of vitamin E on bone health have yielded conflicting and inconclusive results, and to our knowledge, no studies have addressed the effect of vitamin E on bone in animals consuming a high-fat diet (HFD). Objective: This study aimed to evaluate the effect of excessive vitamin E on bone metabolism in normal male mice and ovariectomized female mice fed a normal diet (ND) or HFD. Methods: In the first 2 experiments, 7-wk-old male mice were fed an ND (16% energy from fat) containing 75 (control), 0 (vitamin E-free), or 1000 (high vitamin E) mg vitamin E/kg (experiment 1) or an HFD (46% energy from fat) containing 0, 200, 500, or 1000 mg vitamin E/kg (experiment 2) for 18 wk. In the third experiment, 7-wk-old sham-operated or ovariectomized female mice were fed the ND (75 mg vitamin E/kg) or HFD containing 0 or 1000 mg vitamin E/kg for 8 wk. At the end of the feeding period, blood and femurs were collected to measure bone turnover markers and analyze histology and microcomputed tomography. Results: In experiments 1 and 2, vitamin E intake had no effect on plasma alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activity, or bone formation, resorption, or volume in femurs in mice fed the ND or HFDs. In experiment 3, bone volume was significantly reduced (85%) in ovariectomized mice compared with that in sham-operated mice ( P < 0.05), but it did not differ among mice fed the 3 diets. Plasma ALP and TRAP activities and bone formation and resorption in femur were similar among ovariectomized mice fed the HFD containing 0 or 1000 mg vitamin E/kg. Conclusions: The results suggest that excess vitamin E intake does not cause bone loss in normal male mice or in ovariectomized or sham-operated female mice, regardless of dietary fat content. © 2017 American Society for Nutrition.

Quantitation of mRNAs for α 1-acid glycoprotein and for serum albumin in livers of normal, stressed, fasted, and refed rats. [ 125I or 131I radioimmunoassay for protein products of specific mRNA activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, Linda Jean

1978-01-01

A new procedure for determining the relative levels of a specific mRNA species was developed and applied to mRNA for rat serum albumin (RSA) and α 1-AGP) in rat liver. The method is a radioimmunoassay ( 125In or 131I) for the completed protein, but which also detects antigenic determinants in nascent polypeptide chains on plysomes synthesizing the specific protein. Results show that 24 hs after stressing the rat by turpentine injection the total number of polysomes per mg DNA has increased by 20 to 25%; however, the number of RSA synthesizing polysomes per mg DNA has decreased slightly. In ratsmore » fasted for 6 days, the number of RSA synthesizing polysomes per mg polysomal RNA is only slightly below normal, but the total number of RSA synthesizing polysomes per mg DNA has decreased by 40%. Again, it is seen that RSA mRNA levels do not decrease as sharply as the rate of RSA synthesis. Twelve hours after refeeding the rats, the number of RSA synthesizing polysomes begins to increase, reaching a peak two to three times normal levels 24 to 48 hours after commencement of refeeding. During the first 24 hs after turpentine injection, there is a linear increase in the number of α 1-AGP synthesizing polysomes. The increase is smaller during the next 24 hs and there is a small decrease between 48 and 72 hs. The serum concentrations of α 1-AGP following turpentine treatment reflect these changes in polysome levels. It was not possible to compare the number of α 1-AGP synthesizing polysomes in livers of normal, fasted, and refed rats because the levels detected were only slightly higher than those seen in rat and rat kidney polysome controls. This background activity must be eliminated before the technique can be applied to quantitating mRNA for proteins synthesized in very small quantities. This technique offers several advantages over other procedures commonly used to quantitate mRNA. (ERB)« less

Differential Activities of the Two Closely Related Withanolides, Withaferin A and Withanone: Bioinformatics and Experimental Evidences

PubMed Central

Manjunath, Kavyashree; Uthayakumar, M.; Kanaujia, Shankar P.; Kaul, Sunil C.; Sekar, Kanagaraj; Wadhwa, Renu

2012-01-01

Background and Purpose Withanolides are naturally occurring chemical compounds. They are secondary metabolites produced via oxidation of steroids and structurally consist of a steroid-backbone bound to a lactone or its derivatives. They are known to protect plants against herbivores and have medicinal value including anti-inflammation, anti-cancer, adaptogenic and anti-oxidant effects. Withaferin A (Wi-A) and Withanone (Wi-N) are two structurally similar withanolides isolated from Withania somnifera, also known as Ashwagandha in Indian Ayurvedic medicine. Ashwagandha alcoholic leaf extract (i-Extract), rich in Wi-N, was shown to kill cancer cells selectively. Furthermore, the two closely related purified phytochemicals, Wi-A and Wi-N, showed differential activity in normal and cancer human cells in vitro and in vivo. We had earlier identified several genes involved in cytotoxicity of i-Extract in human cancer cells by loss-of-function assays using either siRNA or randomized ribozyme library. Methodology/Principal Findings In the present study, we have employed bioinformatics tools on four genes, i.e., mortalin, p53, p21 and Nrf2, identified by loss-of-function screenings. We examined the docking efficacy of Wi-N and Wi-A to each of the four targets and found that the two closely related phytochemicals have differential binding properties to the selected cellular targets that can potentially instigate differential molecular effects. We validated these findings by undertaking parallel experiments on specific gene responses to either Wi-N or Wi-A in human normal and cancer cells. We demonstrate that Wi-A that binds strongly to the selected targets acts as a strong cytotoxic agent both for normal and cancer cells. Wi-N, on the other hand, has a weak binding to the targets; it showed milder cytotoxicity towards cancer cells and was safe for normal cells. The present molecular docking analyses and experimental evidence revealed important insights to the use of Wi-A and Wi-N for cancer treatment and development of new anti-cancer phytochemical cocktails. PMID:22973447

Increasing Endocannabinoid Levels in the Ventral Pallidum Restore Aberrant Dopamine Neuron Activity in the Subchronic PCP Rodent Model of Schizophrenia

PubMed Central

Chen, Li; Lodge, Daniel J

2015-01-01

Background: Schizophrenia is a debilitating disorder that affects 1% of the US population. While the exogenous administration of cannabinoids such as tetrahydrocannabinol is reported to exacerbate psychosis in schizophrenia patients, augmenting the levels of endogenous cannabinoids has gained attention as a possible alternative therapy to schizophrenia due to clinical and preclinical observations. Thus, patients with schizophrenia demonstrate an inverse relationship between psychotic symptoms and levels of the endocannabinoid anandamide. In addition, increasing endocannabinoid levels (by blockade of enzymatic degradation) has been reported to attenuate social withdrawal in a preclinical model of schizophrenia. Here we examine the effects of increasing endogenous cannabinoids on dopamine neuron activity in the sub-chronic phencyclidine (PCP) model. Aberrant dopamine system function is thought to underlie the positive symptoms of schizophrenia. Methods: Using in vivo extracellular recordings in chloral hydrate–anesthetized rats, we now demonstrate an increase in dopamine neuron population activity in PCP-treated rats. Results: Interestingly, endocannabinoid upregulation, induced by URB-597, was able to normalize this aberrant dopamine neuron activity. Furthermore, we provide evidence that the ventral pallidum is the site where URB-597 acts to restore ventral tegmental area activity. Conclusions: Taken together, we provide preclinical evidence that augmenting endogenous cannabinoids may be an effective therapy for schizophrenia, acting in part to restore ventral pallidal activity. PMID:25539511

ELECTROMYOGRAPHIC ASSESSMENT OF MUSCLE ACTIVITY BETWEEN GENDERS DURING UNILATERAL WEIGHT‐BEARING TASKS USING ADJUSTED DISTANCES

PubMed Central

Wilhelm, Jacqueline; Eisel, Patricia; Wiesner, Jessica; Rachow, Megan; Hatteberg, Lindsay

2012-01-01

Purpose/Background: Researchers have observed differences in muscle activity patterns between males and females during functional exercises. The research methods employed have used various step heights and lunge distances to assess functional exercise making gender comparisons difficult. The purpose of this study was to examine core and lower extremity muscle activity between genders during single‐limb exercises using adjusted distances and step heights based on a percentage of the participant's height. Methods: Twenty men and 20 women who were recreationally active and healthy participated in the study. Two‐dimensional video and surface electromyography (SEMG) were used to assess performance during three exercise maneuvers (step down, forward lunge, and side‐step lunge). Eight muscles were assessed using SEMG (rectus abdominus, external oblique, erector spinae, rectus femoris, tensor fascia latae, gluteus medius, gluteus maximus, biceps femoris). Maximal voluntary isometric contractions (MVIC) were used for each muscle and expressed as %MVIC to normalize SEMG to account for body mass differences. Exercises were randomized and distances were normalized to the participant's lower limb length. Descriptive statistics, mixed‐model ANOVA, and ICCs with 95% confidence intervals were calculated. Results: Males were taller, heavier, and had longer leg length when compared to the females. No differences in %MVIC activity were found between genders by task across the eight muscles. For both males and females, the step down task resulted in higher %MVIC for gluteus maximus compared to lunge, (p=0.002). Step down exercise produced higher %MVIC for gluteus medius than lunge (p=0.002) and side step (p=0.006). ICC3,3 ranged from moderate to high (0.74 to 0.97) for the three tasks. Conclusions: Muscle activation among the eight muscles was similar between females and males during the lunge, side‐step, and step down tasks, with distances adjusted to leg length. Both males and females elicited higher muscle activity for gluteus maximus and gluteus medius as compared to the trunk, hip flexors, or hamstring muscles. However these values were well below the recruitment levels necessary for strengthening in both genders. Level of evidence: 4 PMID:23316423

Myocardial Adeno-Associated Virus Serotype 6–βARKct Gene Therapy Improves Cardiac Function and Normalizes the Neurohormonal Axis in Chronic Heart Failure

PubMed Central

Rengo, Giuseppe; Lymperopoulos, Anastasios; Zincarelli, Carmela; Donniacuo, Maria; Soltys, Stephen; Rabinowitz, Joseph E.; Koch, Walter J.

2009-01-01

Background The upregulation of G protein–coupled receptor kinase 2 in failing myocardium appears to contribute to dysfunctional β-adrenergic receptor (βAR) signaling and cardiac function. The peptide βARKct, which can inhibit the activation of G protein–coupled receptor kinase 2 and improve βAR signaling, has been shown in transgenic models and short-term gene transfer experiments to rescue heart failure (HF). This study was designed to evaluate long-term βARKct expression in HF with the use of stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6). Methods and Results In HF rats, we delivered βARKct or green fluorescent protein as a control via AAV6-mediated direct intramyocardial injection. We also treated groups with concurrent administration of the β-blocker metoprolol. We found robust and long-term transgene expression in the left ventricle at least 12 weeks after delivery. βARKct significantly improved cardiac contractility and reversed left ventricular remodeling, which was accompanied by a normalization of the neurohormonal (catecholamines and aldosterone) status of the chronic HF animals, including normalization of cardiac βAR signaling. Addition of metoprolol neither enhanced nor decreased βARKct-mediated beneficial effects, although metoprolol alone, despite not improving contractility, prevented further deterioration of the left ventricle. Conclusions Long-term cardiac AAV6-βARKct gene therapy in HF results in sustained improvement of global cardiac function and reversal of remodeling at least in part as a result of a normalization of the neurohormonal signaling axis. In addition, βARKct alone improves outcomes more than a β-blocker alone, whereas both treatments are compatible. These findings show that βARKct gene therapy can be of long-term therapeutic value in HF. PMID:19103992

EGFR-directed Affibody for fluorescence-guided glioma surgery: time-dose analysis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ribeiro de Souza, Ana Luiza; Marra, Kayla; Gunn, Jason R.; Elliott, Jonathan T.; Samkoe, Kimberley S.; Paulsen, Keith D.; Draney, Daniel R.; Feldwisch, Joachim

2016-03-01

The key to fluorescence guided surgical oncology is the ability to create specific contrast between normal and glioma tissue. The blood brain barrier that limits the delivery of substances to the normal brain is broken in tumors, allowing accumulation of agents in the tumor interior. However, for a clinical success, imaging agents should be in the infiltrative edges to minimize the resection of normal brain while enable the removal of tumor. The aberrant overexpression and/or activation of EGFR is associated with many types of cancers, including glioblastoma and the injection of a fluorescent molecule targeted to these receptors would improve tumor contrast during fluorescence guided surgery. Affibody molecules have intentional medium affinity and high potential specificity, which are the desirable features of a good surgical imaging agent. The aim of this study was evaluate the brain/glioma uptake of ABY029 labeled with near-infrared dye IRDye800CW after intravenous injection. Rats were either inoculated with orthotopic implantations of U251 human glioma cell line or PBS (shams control) in the brain. The tumors were allowed to grow for 2-3 weeks before carrying out fluorescent tracer experiments. Fluorescent imaging of ex vivo brain slices from rats was acquired at different time points after infection of fluorescently labeled EGFR-specific affibody to verify which time provided maximal contrast tumor to normal brain. Although the tumor was most clearly visualized after 1h of IRDye800CW-labeled ABY029 injection, the tumor location could be identified from the background after 48h. These results suggest that the NIR-labeled affibody examined shows excellent potential to increase surgical visualization for confirmed EGFR positive tumors.

AKAP13 Rho-GEF and PKD-Binding Domain Deficient Mice Develop Normally but Have an Abnormal Response to β-Adrenergic-Induced Cardiac Hypertrophy

PubMed Central

Spindler, Matthew J.; Burmeister, Brian T.; Huang, Yu; Hsiao, Edward C.; Salomonis, Nathan; Scott, Mark J.; Srivastava, Deepak; Carnegie, Graeme K.; Conklin, Bruce R.

2013-01-01

Background A-kinase anchoring proteins (AKAPs) are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA) and D (PKD) and an active Rho-guanine nucleotide exchange factor (Rho-GEF) domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown. Methodology/Principal Findings To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction. Conclusions These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy. PMID:23658642

Effects of photooxidation on membrane integrity in Salix nigra seeds

PubMed Central

Roqueiro, Gonzalo; Facorro, Graciela B.; Huarte, Mónica G.; Rubín de Celis, Emilio; García, Fernando; Maldonado, Sara; Maroder, Horacio

2010-01-01

Background and Aims Salix nigra seeds are desiccation-tolerant, as are orthodox seeds, although in contrast to other orthodox seeds they lose viability in a few weeks at room temperature. They also differ in that the chloroplasts of the embryo tissues conserve their chlorophyll and endomembranes. The aim of this paper was to investigate the role of chlorophyll in seed deterioration. Methods Seeds were aged at different light intensities and atmospheric conditions. Mean germination time and normal and total germination were evaluated. The formation of free radicals was assessed using electronic spin resonance spectroscopy, and changes in the fatty acid composition from phospholipids, galactolipids and triglycerides using gas–liquid chromatography. Membrane integrity was studied with electronic spin resonance spin probe techniques, electrolyte leakage and transmission electron microscopy. Key Results Light and oxygen played an important role in free-radical generation, causing a decrease in normal germination and an increase in mean germination time. Both indices were associated with a decrease in polyunsaturated fatty acids derived from membrane lipids as phospholipids and galactolipids. The detection of damage in thylakoid membranes and an increase in plasmalemma permeability were consistent with the decrease in both types of lipids. Triglycerides remained unchanged. Light-induced damage began in outermost tissues and spread inwards, decreasing normal germination. Conclusions Salix nigra seeds were very susceptible to photooxidation. The thylakoid membranes appeared to be the first target of the photooxidative process since there were large decreases in galactolipids and both these lipids and the activated chlorophyll are contiguous in the structure of that membrane. Changes in normal germination and mean germination time could be explained by the deteriorative effects of oxidation. PMID:20338949

Does the Relief of Glucose Toxicity Act As a Mediator in Proliferative Actions of Vanadium on Pancreatic Islet Beta Cells in Streptozocin Diabetic Rats?

PubMed Central

Pirmoradi, Leila; Mohammadi, Mohammad Taghi; Safaei, Akbar; Mesbah, Fakhardin; Dehghani, Gholam Abbas

2014-01-01

Background: Data shows vanadium protects pancreatic beta cells (BC) from diabetic animals. Whether this effect is direct or through the relief of glucose toxicity is not clear. This study evaluated the potential effect of oral vanadyl sulfate (vanadium) on glycemic status and pancreatic BC of normal and diabetic rats. Methods: Rats were divided into five groups of normal and diabetic. Diabetes was induced with streptozocin (40 mg/kg, i.v.). Normal rats used water (CN) or vanadium (1 mg/ml VOSO4, VTN). Diabetic rats used water (CD), water plus daily neutral protamine Hagedorn insulin injection (80 U/kg, ITD) or vanadium (VTD). Blood samples were taken for blood glucose (BG, mg/dL) and insulin (ng/dL) measurements. After two months, the pancreata of sacrificed rats were prepared for islet staining. Results: Pre-treated normal BG was 88 ± 2, and diabetic BG was 395 ± 9. The final BG in CD, VTD, and ITD was 509 ± 22, 138 ± 14, and 141 ± 14, respectively. Insulin in VTN (0.75 ± 0.01) and VTD (0.78 ± 0.01) was similar, higher than CD (0.51 ± 0.07) but lower than CN (2.51 ± 0.02). VTN islets compared to CN had larger size and denser central core insulin immunoreactivity with plentiful BC. CD and ITD islets were atrophied and had scattered insulin immunoreactivity spots and low BC mass. VTD islets were almost similar to CN. Conclusion: Besides insulin-like activity, vanadium protected pancreatic islet BC, and the relief of glucose toxicity happening with vanadium had a little role in this action. PMID:24842144

Heavy Smoking Is More Strongly Associated with General Unhealthy Lifestyle than Obesity and Underweight

PubMed Central

Lohse, Tina; Rohrmann, Sabine; Bopp, Matthias; Faeh, David

2016-01-01

Background Smoking and obesity are major causes of non-communicable diseases. We investigated the associations of heavy smoking, obesity, and underweight with general lifestyle to infer which of these risk groups has the most unfavourable lifestyle. Methods We used data from the population-based cross-sectional Swiss Health Survey (5 rounds 1992–2012), comprising 85,575 individuals aged≥18 years. Height, weight, smoking, diet, alcohol intake and physical activity were self-reported. Multinomial logistic regression was performed to analyse differences in lifestyle between the combinations of body mass index (BMI) category and smoking status. Results Compared to normal-weight never smokers (reference), individuals who were normal-weight, obese, or underweight and smoked heavily at the same time had a poorer general lifestyle. The lifestyle of obese and underweight never smokers differed less from reference. Regardless of BMI category, in heavy smoking men and women the fruit and vegetable consumption was lower (e.g. obese heavy smoking men: relative risk ratio (RRR) 1.69 [95% confidence interval 1.30;2.21]) and high alcohol intake was more common (e.g. normal-weight heavy smoking women 5.51 [3.71;8.20]). In both sexes, physical inactivity was observed more often in heavy smokers and obese or underweight (e.g. underweight never smoking 1.29 [1.08;1.54] and heavy smoking women 2.02 [1.33;3.08]). A decrease of smoking prevalence was observed over time in normal-weight, but not in obese individuals. Conclusions Unhealthy general lifestyle was associated with both heavy smoking and BMI extremes, but we observed a stronger association for heavy smoking. Future smoking prevention measures should pay attention to improvement of general lifestyle and co-occurrence with obesity and underweight. PMID:26910775

What Goes Around Can Come Around: An Unexpected Deleterious Effect of Using Mouse Running Wheels for Environmental Enrichment

PubMed Central

Leduc, Renee Y M; Rauw, Gail; Baker, Glen B; McDermid, Heather E

2017-01-01

Environmental enrichment items such as running wheels can promote the wellbeing of laboratory mice. Growing evidence suggests that wheel running simulates exercise effects in many mouse models of human conditions, but this activity also might change other aspects of mouse behavior. In this case study, we show that the presence of running wheels leads to pronounced and permanent circling behavior with route-tracing in a proportion of the male mice of a genetically distinct cohort. The genetic background of this cohort includes a mutation in Arhgap19, but genetic crosses showed that an unknown second-site mutation likely caused the induced circling behavior. Behavioral tests for inner-ear function indicated a normal sense of gravity in the circling mice. However, the levels of dopamine, serotonin, and some dopamine metabolites were lower in the brains of circling male mice than in mice of the same genetic background that were weaned without wheels. Circling was seen in both singly and socially housed male mice. The additional stress of fighting may have exacerbated the predisposition to circling in the socially housed animals. Singly and socially housed male mice without wheels did not circle. Our current findings highlight the importance and possibly confounding nature of the environmental and genetic background in mouse behavioral studies, given that the circling behavior and alterations in dopamine and serotonin levels in this mouse cohort occurred only when the male mice were housed with running wheels. PMID:28315651

Relative arrival-time upper-mantle tomography and the elusive background mean

NASA Astrophysics Data System (ADS)

Bastow, Ian D.

2012-08-01

The interpretation of seismic tomographic images of upper-mantle seismic wave speed structure is often a matter of considerable debate because the observations can usually be explained by a range of hypotheses, including variable temperature, composition, anisotropy, and the presence of partial melt. An additional problem, often overlooked in tomographic studies using relative as opposed to absolute arrival-times, is the issue of the resulting velocity model's zero mean. In shield areas, for example, relative arrival-time analysis strips off a background mean velocity structure that is markedly fast compared to the global average. Conversely, in active areas, the background mean is often markedly slow compared to the global average. Appreciation of this issue is vital when interpreting seismic tomographic images: 'high' and 'low' velocity anomalies should not necessarily be interpreted, respectively, as 'fast' and 'slow' compared to 'normal mantle'. This issue has been discussed in the seismological literature in detail over the years, yet subsequent tomography studies have still fallen into the trap of mis-interpreting their velocity models. I highlight here some recent examples of this and provide a simple strategy to address the problem using constraints from a recent global tomographic model, and insights from catalogues of absolute traveltime anomalies. Consultation of such absolute measures of seismic wave speed should be routine during regional tomographic studies, if only for the benefit of the broader Earth Science community, who readily follow the red = hot and slow, blue = cold and fast rule of thumb when interpreting the images for themselves.

[EMG activities of the head, neck and upper trunk muscles with mandibular movements in healthy adults and mandibular asymmetry patients].

PubMed

Jiang, Ting; Zhang, Zhenkang; Yang, Zhaohui; Yi, Biao; Feng, Hailan; Wang, Xing

2002-03-25

To study the activities of head, neck and upper trunk muscles during mandibular movements in healthy adults and mandibular asymmetry patients. Electromyographic integrogram was used to record and analyze the electromyographic activities of the anterior temporal (Ta), posterior temporal (Tp), sternocleidomastoid (SCM), and trapezius (TRAP) muscles in rest position and during mandibular movement among 10 normal adults and 10 mandibular asymmetry patients. All the four muscles showed constant electromyographic activities when the mandible was in the rest position. The activities of Ta, Tp, and SCM muscles increased with protrusion of mandible, mouth opening, tapping, maximum clenching, and chewing. The activities of Ta and Tp muscles of the patients were 1.7 times greater than that of the normal adults during mandibular movement without occlusion, and were weaker by 50% during mandibular movement with occlusion. The difference between electromyographic activities during mandibular movement and in rest position was less among patients than among normal adults. The TRAP muscle of the patients showed constant electromyographic activities with the activity volume nearly 1.8 times that of the normal adults. The difference between the muscle and its namesake at the opposite side was greater among the patients (21%) than among the normal adults (8%). All the four muscles participate in the maintenance of rest position of mandible and the realization of mandibular movements. The coordination of muscular activities among mandibular asymmetry patients is poorer than that among normal adults.

Physical activity patterns in morbidly obese and normal-weight women.

PubMed

Kwon, Soyang; Mohammad, Jamal; Samuel, Isaac

2011-01-01

To compare physical activity patterns between morbidly obese and normal-weight women. Daily physical activity of 18 morbidly obese and 7 normal-weight women aged 30-58 years was measured for 2 days using the Intelligent Device for Energy Expenditure and Activity (IDEEA) device. The obese group spent about 2 hr/day less standing and 30 min/day less walking than did the normal-weight group. Time spent standing (standing time) was positively associated with time spent walking (walking time). Age- and walking time-adjusted standing time did not differ according to weight status. Promoting standing may be a strategy to increase walking.

75 FR 9613 - Importer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-03

... for the treatment of wounds which contain trace amounts of the controlled substance normally found in..., and a review of the company's background and history. Therefore, pursuant to 21 U.S.C. 952(a) and 958...

Tin Cans Revisited.

ERIC Educational Resources Information Center

Verderber, Nadine L.

1992-01-01

Presents the use of spreadsheets as an alternative method for precalculus students to solve maximum or minimum problems involving surface area and volume. Concludes that students with less technical backgrounds can solve problems normally requiring calculus and suggests sources for additional problems. (MDH)

Readability of self-illuminated signs in a smoke-obscured environment.

DOT National Transportation Integrated Search

1979-11-01

This study investigates the ability of people with normal distant visual acuity to identify self-illuminated emergency signs in a smoke-obscured environment. The results indicate that signs whose background luminance meets or exceeds the requirements...

Instrumented roll technology for the design space development of roller compaction process.

PubMed

Nesarikar, Vishwas V; Vatsaraj, Nipa; Patel, Chandrakant; Early, William; Pandey, Preetanshu; Sprockel, Omar; Gao, Zhihui; Jerzewski, Robert; Miller, Ronald; Levin, Michael

2012-04-15

Instrumented roll technology on Alexanderwerk WP120 roller compactor was developed and utilized successfully for the measurement of normal stress on ribbon during the process. The effects of process parameters such as roll speed (4-12 rpm), feed screw speed (19-53 rpm), and hydraulic roll pressure (40-70 bar) on normal stress and ribbon density were studied using placebo and active pre-blends. The placebo blend consisted of 1:1 ratio of microcrystalline cellulose PH102 and anhydrous lactose with sodium croscarmellose, colloidal silicon dioxide, and magnesium stearate. The active pre-blends were prepared using various combinations of one active ingredient (3-17%, w/w) and lubricant (0.1-0.9%, w/w) levels with remaining excipients same as placebo. Three force transducers (load cells) were installed linearly along the width of the roll, equidistant from each other with one transducer located in the center. Normal stress values recorded by side sensors and were lower than normal stress values recorded by middle sensor and showed greater variability than middle sensor. Normal stress was found to be directly proportional to hydraulic pressure and inversely to screw to roll speed ratio. For active pre-blends, normal stress was also a function of compressibility. For placebo pre-blends, ribbon density increased as normal stress increased. For active pre-blends, in addition to normal stress, ribbon density was also a function of gap. Models developed using placebo were found to predict ribbon densities of active blends with good accuracy and the prediction error decreased as the drug concentration of active blend decreased. Effective angle of internal friction and compressibility properties of active pre blend may be used as key indicators for predicting ribbon densities of active blend using placebo ribbon density model. Feasibility of on-line prediction of ribbon density during roller compaction was demonstrated using porosity-pressure data of pre-blend and normal stress measurements. Effect of vacuum to de-aerate pre blend prior to entering the nip zone was studied. Varying levels of vacuum for de-aeration of placebo pre blend did not affect the normal stress values. However, turning off vacuum completely caused an increase in normal stress with subsequent decrease in gap. Use of instrumented roll demonstrated potential to reduce the number of DOE runs by enhancing fundamental understanding of relationship between normal stress on ribbon and process parameters. Copyright © 2012 Elsevier B.V. All rights reserved.

Cerebral activation evoked by the mirror illusion of the hand in stroke patients compared to normal subjects.

PubMed

Wang, Jing; Fritzsch, Claire; Bernarding, Johannes; Krause, Thomas; Mauritz, Karl-Heinz; Brunetti, Maddalena; Dohle, Christian

2013-01-01

Mirror therapy (MT) was found to improve motor function after stroke, but its neural mechanisms remain unclear, especially in single stroke patients. The following imaging study was designed to compare brain activation patterns evoked by the mirror illusion in single stroke patients with normal subjects. Fifteen normal volunteers and five stroke patients with severe arm paresis were recruited. Cerebral activations during movement mirroring by means of a video chain were recorded with functional magnetic resonance imaging (fMRI). Single-subject analysis was performed using SPM 8. For normal subjects, ten and thirteen subjects displayed lateralized cerebral activations evoked by the mirror illusion while moving their right and left hand respectively. The magnitude of this effect in the precuneus contralateral to the seen hand was not dependent on movement speed or subjective experience. Negative correlation of activation strength with age was found for the right hand only. The activation pattern in stroke patients is comparable to that of normal subjects and present in four out of five patients. In summary, the mirror illusion can elicit cerebral activation contralateral to the perceived hand in the majority of single normal subjects, but not in all of them. This is similar even in stroke patients with severe hemiparesis.

Elevated Acoustic Startle Responses in Humans: Relationship to Reduced Loudness Discomfort Level, but not Self-Report of Hyperacusis.

PubMed

Knudson, Inge M; Melcher, Jennifer R

2016-06-01

Increases in the acoustic startle response (ASR) of animals have been reported following experimental manipulations to induce tinnitus, an auditory disorder defined by phantom perception of sound. The increases in ASR have been proposed to signify the development of hyperacusis, a clinical condition defined by intolerance of normally tolerable sound levels. To test this proposal, the present study compared ASR amplitude to measures of sound-level tolerance (SLT) in humans, the only species in which SLT can be directly assessed. Participants had clinically normal/near-normal hearing thresholds, were free of psychotropic medications, and comprised people with tinnitus and without. ASR was measured as eyeblink-related electromyographic activity in response to a noise pulse presented at a range of levels and in two background conditions (noise and quiet). SLT was measured as loudness discomfort level (LDL), the lowest level of sound deemed uncomfortable, and via a questionnaire on the loudness of sounds in everyday life. Regardless of tinnitus status, ASR amplitude at a given stimulus level increased with decreasing LDL, but showed no relationship to SLT self-reported via the questionnaire. These relationships (or lack thereof) could not be attributed to hearing threshold, age, anxiety, or depression. The results imply that increases in ASR in the animal work signify decreases in LDL specifically and may not correspond to the development of hyperacusis as would be self-reported by a clinic patient.

An overview of systematic reviews of normal labor and delivery management

PubMed Central

Iravani, Mina; Janghorbani, Mohsen; Zarean, Elahe; Bahrami, Masoud

2015-01-01

Background: Despite the scientific and medical advances for management of complicated health issues, the current maternity care setting has increased risks for healthy women and their babies. The aim of this study was to conduct an overview of published systematic reviews on the interventions used most commonly for management of normal labor and delivery in the first stage of labor. Materials and Methods: The online databases through March 2013, limited to systematic reviews of clinical trials were searched. An updated search was performed in April 2014. Two reviewers independently assessed data inclusion, extraction, and quality of methodology. Results: Twenty-three reviews (16 Cochrane, 7 non-Cochrane), relating to the most common care practices for management of normal labor and delivery in the first stage of labor, were included. Evidence does not support routine enemas, routine perineal shaving, continuous electronic fetal heart rate monitoring, routine early amniotomy, and restriction of fluids and food during labor. Evidence supports continuity of midwifery care and support, encouragement to non-supine position, and freedom in movement throughout labor. There is insufficient evidence to support routine administration of intravenous fluids and antispasmodics during labor. More evidence is needed regarding delayed admission until active labor and use of partograph. Conclusions: Evidence-based maternity care emphasizes on the practices that increase safety for mother and baby. If policymakers and healthcare providers wish to promote obstetric care quality successfully, it is important that they implement evidence-based clinical practices in routine midwifery care. PMID:26120327

Bhlhb5 is Required for the Subtype Development of Retinal Amacrine and Bipolar Cells in Mice

PubMed Central

Huang, Liang; Hu, Fang; Feng, Liang; Luo, Xiong-Jian; Liang, Guoqing; Zeng, Xiang-Yun; Yi, Jing-Lin; Gan, Lin

2014-01-01

Background BHLHB5, an OLIG-related basic helix-loop-helix transcription factor, is required for the development of a subset of gamma-amino butyric acid–releasing (GABAergic) amacrine cells and OFF-cone bipolar (CB) cells in mouse retinas. In order to determine BHLHB5’s functional mechanism in retinogenesis, we used the Cre-loxP recombination system to genetically trace the lineage of BHLHB5+ cells in normal and Bhlhb5-null retinas. The Bhlhb5-Cre knock-in allele was used to activate the constitutive expression of a GFP reporter in the Bhlhb5-expressing cells, and the cell fates of Bhlhb5-lineage cells were identified by using specific cell markers and were compared between normal and Bhlhb5-null retinas. Results In addition to GABAergic amacrine and OFF-CB cells, Bhlhb5 lineage cells give rise to ganglion, glycinergic amacrine, rod bipolar, ON-bipolar, and rod photoreceptor cells during normal retinal development. Targeted deletion of Bhlhb5 resulted in the loss of GABAergic amacrine, glycinergic amacrine, dopaminergic amacrine, and Type 2 OFF-CB cells. Furthermore, in the absence of BHLHB5, a portion of Bhlhb5 lineage cells switch their fate and differentiate into cholinergic amacrine cells. Conclusions Our data reveal a broad expression pattern of Bhlhb5 throughout retinogenesis and demonstrate the cell-autonomous as well as non-cell-autonomous role of Bhlhb5 in the specification of amacrine and bipolar subtypes. PMID:24123365

Murine colon proteome and characterization of the protein pathways

PubMed Central

2012-01-01

Background Most of the current proteomic researches focus on proteome alteration due to pathological disorders (i.e.: colorectal cancer) rather than normal healthy state when mentioning colon. As a result, there are lacks of information regarding normal whole tissue- colon proteome. Results We report here a detailed murine (mouse) whole tissue- colon protein reference dataset composed of 1237 confident protein (FDR < 2) with comprehensive insight on its peptide properties, cellular and subcellular localization, functional network GO annotation analysis, and its relative abundances. The presented dataset includes wide spectra of pI and Mw ranged from 3–12 and 4–600 KDa, respectively. Gravy index scoring predicted 19.5% membranous and 80.5% globularly located proteins. GO hierarchies and functional network analysis illustrated proteins function together with their relevance and implication of several candidates in malignancy such as Mitogen- activated protein kinase (Mapk8, 9) in colorectal cancer, Fibroblast growth factor receptor (Fgfr 2), Glutathione S-transferase (Gstp1) in prostate cancer, and Cell division control protein (Cdc42), Ras-related protein (Rac1,2) in pancreatic cancer. Protein abundances calculated with 3 different algorithms (NSAF, PAF and emPAI) provide a relative quantification under normal condition as guidance. Conclusions This highly confidence colon proteome catalogue will not only serve as a useful reference for further experiments characterizing differentially expressed proteins induced from diseased conditions, but also will aid in better understanding the ontology and functional absorptive mechanism of the colon as well. PMID:22929016

The potential application of a transcriptionally regulated oncolytic herpes simplex virus for human cancer therapy

PubMed Central

Miao, L; Fraefel, C; Sia, K C; Newman, J P; Mohamed-Bashir, S A; Ng, W H; Lam, P Y P

2014-01-01

Background: Emerging studies have shown the potential benefit of arming oncolytic viruses with therapeutic genes. However, most of these therapeutic genes are placed under the regulation of ubiquitous viral promoters. Our goal is to generate a safer yet potent oncolytic herpes simplex virus type-1 (HSV-1) for cancer therapy. Methods: Using bacterial artificial chromosome (BAC) recombineering, a cell cycle-regulatable luciferase transgene cassette was replaced with the infected cell protein 6 (ICP6) coding region (encoded for UL39 or large subunit of ribonucleotide reductase) of the HSV-1 genome. These recombinant viruses, YE-PC8, were further tested for its proliferation-dependent luciferase gene expression. Results: The ability of YE-PC8 to confer proliferation-dependent transgene expression was demonstrated by injecting similar amount of viruses into the tumour-bearing region of the brain and the contralateral normal brain parenchyma of the same mouse. The results showed enhanced levels of luciferase activities in the tumour region but not in the normal brain parenchyma. Similar findings were observed in YE-PC8-infected short-term human brain patient-derived glioma cells compared with normal human astrocytes. intratumoural injection of YE-PC8 viruses resulted in 77% and 80% of tumour regression in human glioma and human hepatocellular carcinoma xenografts, respectively. Conclusion: YE-PC8 viruses confer tumour selectivity in proliferating cells and may be developed further as a feasible approach to treat human cancers. PMID:24196790

Antimicrobial effects of chlorhexidine, matrica drop mouthwash (chamomile extract), and normal saline on hospitalized patients with endotracheal tubes

PubMed Central

Azimi, Maryam; Jouybari, Leila; Moghadam, Shahram; Ghaemi, Ezatolah; Behnampoor, Naser; Sanagoo, Akram; Hesam, Moslem

2016-01-01

Background: The functions and use of mouthwashes are variable depending on their type. Oral care in patients with endotracheal tubes is important to prevent side effects such as pneumonia. The aim of this study was to determine the antimicrobial effects of chlorhexidine, drop of Matrica mouthwash (chamomile extract), and normal saline on hospitalized patients with endotracheal tube in an intensive care unit (ICU). Materials and Methods: In this clinical trial, 39 patients admitted to the ICU were selected by convenience sampling, were matched based on age and sex, and randomly assigned to three groups (chlorhexidine, Matrica, saline). Mouth washing was performed every 8 to 48 hours. The samples were taken at time zero (before the intervention) and 48 hours after the intervention for bacterial culture. Antibacterial activity of each mouthwash on microorganisms was measured based on the growth of Staphylococcus aureus, Pneumococcal, Enterococcus, Pseudomonas, and Escherichia coli. The obtained data were then analyzed using Chi-square and Fisher's exact tests with the Statistical Package for the Social Sciences Package version 18. Results: Chlorhexidine mouthwash was more effective in preventing colonization of bacteria in the mouth (point probability = 0.06) in comparison with chamomile and saline mouthwashes. Nevertheless, none of the tested mouthwashes were able to remove pathogens, including Staphylococcus aureus, Pseudomonas, Klebsiella, and Acinetobacter. Conclusions: 0.2% chlorhexidine mouthwash has a significant effect on the bacterial colonization rate in comparison with Matrica and normal saline mouthwashes in ICU hospitalized patients with endotracheal tube. PMID:27904627

Reconstitution of the ERG Gene Expression Network Reveals New Biomarkers and Therapeutic Targets in ERG Positive Prostate Tumors

PubMed Central

Dubovenko, Alexey; Serebryiskaya, Tatiana; Nikolsky, Yuri; Nikolskaya, Tatiana; Perlina, Ally; JeBailey, Lellean; Bureeva, Svetlana; Katta, Shilpa; Srivastava, Shiv; Dobi, Albert; Khasanova, Tatiana

2015-01-01

Background: Despite a growing number of studies evaluating cancer of prostate (CaP) specific gene alterations, oncogenic activation of the ETS Related Gene (ERG) by gene fusions remains the most validated cancer gene alteration in CaP. Prevalent gene fusions have been described between the ERG gene and promoter upstream sequences of androgen-inducible genes, predominantly TMPRSS2 (transmembrane protease serine 2). Despite the extensive evaluations of ERG genomic rearrangements, fusion transcripts and the ERG oncoprotein, the prognostic value of ERG remains to be better understood. Using gene expression dataset from matched prostate tumor and normal epithelial cells from an 80 GeneChip experiment examining 40 tumors and their matching normal pairs in 40 patients with known ERG status, we conducted a cancer signaling-focused functional analysis of prostatic carcinoma representing moderate and aggressive cancers stratified by ERG expression. Results: In the present study of matched pairs of laser capture microdissected normal epithelial cells and well-to-moderately differentiated tumor epithelial cells with known ERG gene expression status from 20 patients with localized prostate cancer, we have discovered novel ERG associated biochemical networks. Conclusions: Using causal network reconstruction methods, we have identified three major signaling pathways related to MAPK/PI3K cascade that may indeed contribute synergistically to the ERG dependent tumor development. Moreover, the key components of these pathways have potential as biomarkers and therapeutic target for ERG positive prostate tumors. PMID:26000039

Inner ear dysfunction in caspase-3 deficient mice

PubMed Central

2011-01-01

Background Caspase-3 is one of the most downstream enzymes activated in the apoptotic pathway. In caspase-3 deficient mice, loss of cochlear hair cells and spiral ganglion cells coincide closely with hearing loss. In contrast with the auditory system, details of the vestibular phenotype have not been characterized. Here we report the vestibular phenotype and inner ear anatomy in the caspase-3 deficient (Casp3-/-) mouse strain. Results Average ABR thresholds of Casp3-/- mice were significantly elevated (P < 0.05) compared to Casp3+/- mice and Casp3+/+ mice at 3 months of age. In DPOAE testing, distortion product 2F1-F2 was significantly decreased (P < 0.05) in Casp3-/- mice, whereas Casp3+/- and Casp3+/+ mice showed normal and comparable values to each other. Casp3-/- mice were hyperactive and exhibited circling behavior when excited. In lateral canal VOR testing, Casp3-/- mice had minimal response to any of the stimuli tested, whereas Casp3+/- mice had an intermediate response compared to Casp3+/+ mice. Inner ear anatomical and histological analysis revealed gross hypomorphism of the vestibular organs, in which the main site was the anterior semicircular canal. Hair cell numbers in the anterior- and lateral crista, and utricle were significantly smaller in Casp3-/- mice whereas the Casp3+/- and Casp3+/+ mice had normal hair cell numbers. Conclusions These results indicate that caspase-3 is essential for correct functioning of the cochlea as well as normal development and function of the vestibule. PMID:21988729

Impact of serum-derived bovine immunoglobulin/protein isolate therapy on irritable bowel syndrome and inflammatory bowel disease: a survey of patient perspective

PubMed Central

Shaw, Audrey L; Tomanelli, Adam; Bradshaw, Timothy P; Petschow, Bryon W; Burnett, Bruce P

2017-01-01

Background Patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD) commonly experience diarrhea, abdominal pain, bloating, and urgency. These symptoms significantly compromise the patient’s quality of life (QoL) by limiting participation in normal daily activities and adversely affect work productivity and performance. Purpose The aim of this study was to understand from the patient’s perspective how oral serum-derived bovine immunoglobulin/protein isolate (SBI) impacts bowel habits, management of condition, and basic QoL. Methods A 1-page questionnaire was distributed randomly to >14,000 patients who were prescribed SBI (EnteraGam®) for relevant intended uses. The survey was designed to collect data related to the influence of IBS or IBD on daily life activities and the impact of SBI usage on daily stool frequency, management of their condition, and QoL. Patient-reported responses were analyzed using a paired t-test to compare mean change in daily stool output and descriptive statistics for continuous variables. Results A total of 1,377 patients returned the surveys. Results from 595 surveys were analyzed with a focus on patients with IBS or IBD who had provided numeric responses regarding daily stool frequency. Respondents with IBS who reported having a normal stool frequency (≤4 stools per day) increased from 35% prior to using SBI to 91% while using SBI. A similar change toward normal stool frequency was reported by IBD respondents. Mean daily stool numbers decreased for respondents in the combined IBS and IBD groups (P=0.0001) from 6.5±4.3 before SBI to 2.6±1.9 following SBI use. The majority of respondents agreed strongly or very strongly that SBI helped them manage their condition (66.9%) and helped them return to the activities they enjoyed (59.1%). Conclusion Results from this patient survey suggest that SBI use can lead to clinically relevant decreases in daily stool frequency in patients with IBS or IBD along with improvements in the overall management of their condition and aspects of QoL. PMID:28615929

Monitoring of treatment with vitamin K antagonists: recombinant thromboplastins are more sensitive to factor VII than tissue-extract thromboplastins.

PubMed

Biedermann, J S; van den Besselaar, A M H P; de Maat, M P M; Leebeek, F W G; Kruip, M J H A

2017-03-01

Essentials Differences in sensitivity to factor VII (FVII) have been suggested between thromboplastins. FVII-induced International Normalized Ratio (INR) changes differ between commercial reagents. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Thromboplastin choice may affect FVII-mediated INR stability. Background Differences regarding sensitivity to factor VII have been suggested for recombinant human and tissue-extract thromboplastins used for International Normalized Ratio (INR) measurement, but the evidence is scarce. Differences in FVII sensitivity are clinically relevant, as they can affect INR stability during treatment with vitamin K antagonists (VKAs). Objectives To determine whether commercial thromboplastins react differently to changes in FVII. Methods We studied the effect of addition of FVII on the INR in plasma by using three tissue-extract (Neoplastin C1+, Hepato Quick, and Thromborel S) and three recombinant human (Recombiplastin 2G, Innovin, and CoaguChek XS) thromboplastins. Three different concentrations of purified human FVII (0.006, 0.012 and 0.062 μg mL -1 plasma), or buffer, were added to five certified pooled plasmas of patients using VKAs (INR of 1.5-3.5). Changes in FVII activity were measured with two bioassays (Neoplastin and Recombiplastin), and relative INR changes were compared between reagents. Results After addition of 0.062 μg mL -1 FVII, FVII activity in the pooled plasmas increased by approximately 20% (Neoplastin) or 32% (Recombiplastin) relative to the activity in pooled normal plasma. All thromboplastins showed dose-dependent INR decreases. The relative INR change in the pooled plasmas significantly differed between the six thromboplastins. No differences were observed among recombinant or tissue-extract thromboplastins. Pooled results indicated that the FVII-induced INR change was greater for recombinant than for tissue-extract thromboplastins. Conclusions Differences regarding FVII sensitivity exist between various thromboplastins used for VKA monitoring. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Therefore, thromboplastin choice may affect FVII-mediated INR stability. © 2017 International Society on Thrombosis and Haemostasis.

Systolic ventricular filling.

PubMed

Torrent-Guasp, Francisco; Kocica, Mladen J; Corno, Antonio; Komeda, Masashi; Cox, James; Flotats, A; Ballester-Rodes, Manel; Carreras-Costa, Francesc

2004-03-01

The evidence of the ventricular myocardial band (VMB) has revealed unavoidable coherence and mutual coupling of form and function in the ventricular myocardium, making it possible to understand the principles governing electrical, mechanical and energetical events within the human heart. From the earliest Erasistratus' observations, principal mechanisms responsible for the ventricular filling have still remained obscured. Contemporary experimental and clinical investigations unequivocally support the attitude that only powerful suction force, developed by the normal ventricles, would be able to produce an efficient filling of the ventricular cavities. The true origin and the precise time frame for generating such force are still controversial. Elastic recoil and muscular contraction were the most commonly mentioned, but yet, still not clearly explained mechanisms involved in the ventricular suction. Classical concepts about timing of successive mechanical events during the cardiac cycle, also do not offer understandable insight into the mechanism of the ventricular filling. The net result is the current state of insufficient knowledge of systolic and particularly diastolic function of normal and diseased heart. Here we summarize experimental evidence and theoretical backgrounds, which could be useful in understanding the phenomenon of the ventricular filling. Anatomy of the VMB, and recent proofs for its segmental electrical and mechanical activation, undoubtedly indicates that ventricular filling is the consequence of an active muscular contraction. Contraction of the ascendent segment of the VMB, with simultaneous shortening and rectifying of its fibers, produces the paradoxical increase of the ventricular volume and lengthening of its long axis. Specific spatial arrangement of the ascendent segment fibers, their interaction with adjacent descendent segment fibers, elastic elements and intra-cavitary blood volume (hemoskeleton), explain the physical principles involved in this action. This contraction occurs during the last part of classical systole and the first part of diastole. Therefore, the most important part of ventricular diastole (i.e. the rapid filling phase), in which it receives >70% of the stroke volume, belongs to the active muscular contraction of the ascendent segment. We hope that these facts will give rise to new understanding of the principal mechanisms involved in normal and abnormal diastolic heart function.

Intensive language training enhances brain plasticity in chronic aphasia

PubMed Central

Meinzer, Marcus; Elbert, Thomas; Wienbruch, Christian; Djundja, Daniela; Barthel, Gabriela; Rockstroh, Brigitte

2004-01-01

Background Focal clusters of slow wave activity in the delta frequency range (1–4 Hz), as measured by magnetencephalography (MEG), are usually located in the vicinity of structural damage in the brain. Such oscillations are usually considered pathological and indicative of areas incapable of normal functioning owing to deafferentation from relevant input sources. In the present study we investigated the change in Delta Dipole Density in 28 patients with chronic aphasia (>12 months post onset) following cerebrovascular stroke of the left hemisphere before and after intensive speech and language therapy (3 hours/day over 2 weeks). Results Neuropsychologically assessed language functions improved significantly after training. Perilesional delta activity decreased after therapy in 16 of the 28 patients, while an increase was evident in 12 patients. The magnitude of change of delta activity in these areas correlated with the amount of change in language functions as measured by standardized language tests. Conclusions These results emphasize the significance of perilesional areas in the rehabilitation of aphasia even years after the stroke, and might reflect reorganisation of the language network that provides the basis for improved language functions after intensive training. PMID:15331014

Altered Neural Correlate of the Self-Agency Experience in First-Episode Schizophrenia-Spectrum Patients: An fMRI Study

PubMed Central

Spaniel, Filip; Tintera, Jaroslav; Rydlo, Jan; Ibrahim, Ibrahim; Kasparek, Tomas; Horacek, Jiri; Zaytseva, Yuliya; Matejka, Martin; Fialova, Marketa; Slovakova, Andrea; Mikolas, Pavol; Melicher, Tomas; Görnerova, Natalie; Höschl, Cyril; Hajek, Tomas

2016-01-01

Background: The phenomenology of the clinical symptoms indicates that disturbance of the sense of self be a core marker of schizophrenia. Aims: To compare neural activity related to the self/other-agency judgment in patients with first-episode schizophrenia-spectrum disorders (FES, n = 35) and healthy controls (HC, n = 35). Method: A functional magnetic resonance imaging (fMRI) using motor task with temporal distortion of the visual feedback was employed. A task-related functional connectivity was analyzed with the use of independent component analysis (ICA). Results: (1) During self-agency experience, FES showed a deficit in cortical activation in medial frontal gyrus (BA 10) and posterior cingulate gyrus, (BA 31; P < .05, Family-Wise Error [FWE] corrected). (2) Pooled-sample task-related ICA revealed that the self/other-agency judgment was dependent upon anti-correlated default mode and central-executive networks (DMN/CEN) dynamic switching. This antagonistic mechanism was substantially impaired in FES during the task. Discussion: During self-agency experience, FES demonstrate deficit in engagement of cortical midline structures along with substantial attenuation of anti-correlated DMN/CEN activity underlying normal self/other-agency discriminative processes. PMID:26685867

Impact of Active Control on Passive Safety Response Characteristics of Sodium-cooled Fast Reactors: I - Theoretical background

DOE Office of Scientific and Technical Information (OSTI.GOV)

Passerini, Stefano; Ponciroli, Roberto; Vilim, Richard B.

Here, the interaction of the active control system with passive safety behavior is investigated for sodium-cooled fast reactors. A claim often made of advanced reactors is that they are passively safe against unprotected upset events. In practice, such upset events are not analyzed in the context of the plant control system, but rather the analyses are performed without considering the normally programmed response of the control system (open-loop approach). This represents an oversimplification of the safety case. The issue of passive safety override arises since the control system commands actuators whose motions have safety consequences. Depending on the upset involvingmore » the control system ( operator error, active control system failure, or inadvertent control system override), an actuator does not necessarily go in the same direction as needed for safety. So neglecting to account for control system action during an unprotected upset is nonconservative from a safety standpoint. It is important then, during the design of the plant, to consider the potential for the control system to work against the inherent and safe regulating effects of purposefully engineered temperature feedbacks.« less

[Dietary interventions and social care for treating obesity in children].

PubMed

Wiegand, S; Bau, A-M; Babitsch, B

2011-05-01

The prevalence of obesity and associated comorbidities among children and adolescents has risen worldwide throughout the past 3 decades. To break this trend, population-based activities in health promotion/prevention and health care are necessary. Studies showed that long-term eating behavior improvement with the cooperation of the patient's family together with child-friendly organization support both individual therapeutic improvements as well as a relevant reduction of obesity prevalence. A significant BMI reduction can be achieved with a normal varied diet, whose energetic value is 300-400 kcal/day below the patient's daily energetic needs, due to the lower consumption of fat and sugar. This requires, however, that the entire family be willing to change their unhealthy eating behaviors (e.g., soft drinks and fast food) and to introduce regular meals into their daily routine. Sensibly, most therapies combine diet therapy with increased physical activity and parental training. Controlled media consumption, active leisure-time behavior, and a structured daily routine are further conditions for successful weight reduction. The high-risk groups for pediatric obesity, i.e., families with migration background and/or low socioeconomic status, have been poorly reached by established programs.

Impact of Active Control on Passive Safety Response Characteristics of Sodium-cooled Fast Reactors: I - Theoretical background

DOE PAGES

Passerini, Stefano; Ponciroli, Roberto; Vilim, Richard B.

2017-06-21

Here, the interaction of the active control system with passive safety behavior is investigated for sodium-cooled fast reactors. A claim often made of advanced reactors is that they are passively safe against unprotected upset events. In practice, such upset events are not analyzed in the context of the plant control system, but rather the analyses are performed without considering the normally programmed response of the control system (open-loop approach). This represents an oversimplification of the safety case. The issue of passive safety override arises since the control system commands actuators whose motions have safety consequences. Depending on the upset involvingmore » the control system ( operator error, active control system failure, or inadvertent control system override), an actuator does not necessarily go in the same direction as needed for safety. So neglecting to account for control system action during an unprotected upset is nonconservative from a safety standpoint. It is important then, during the design of the plant, to consider the potential for the control system to work against the inherent and safe regulating effects of purposefully engineered temperature feedbacks.« less

Status of metal levels and their potential sources of contamination in Southeast Asian rivers.

PubMed

Chanpiwat, Penradee; Sthiannopkao, Suthipong

2014-01-01

To assess the concentration and status of metal contaminants in four major Southeast Asian river systems, water were collected from the Tonle Sap-Bassac Rivers (Cambodia), Citarum River (Indonesia), lower Chao Phraya River (Thailand), and Saigon River (Vietnam) in both dry and wet seasons. The target elements were Be, Al, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Ag, Cd, Ba, Tl, and Pb and the concentrations exceeded the background metal concentrations by 1- to 88-fold. This distinctly indicates enrichment by human urban area activities. The results of a normalization technique used to distinguish natural from enriched metal concentrations confirmed contamination by Al, Cd, Co, Mn, Ni, Pb, and Zn. Cluster analysis revealed the probable source of metals contamination in most sampling sites on all rivers studied to be anthropogenic, including industrial, commercial, and residential activities. Stable lead isotopes analyses applied to track the sources and pathways of anthropogenic lead furthermore confirmed that anthropogenic sources of metal contaminated these rivers. Discharges of wastewater from both industrial and household activities were major contributors of Pb into the rivers. Non-point sources, especially road runoff and street dust, also contributed contamination from Pb and other metals.

What are the implications of rapid global warming for landslide-triggered turbidity current activity?

NASA Astrophysics Data System (ADS)

Clare, Michael; Peter, Talling; James, Hunt

2014-05-01

A geologically short-lived (~170kyr) episode of global warming occurred at ~55Ma, termed the Initial Eocene Thermal Maximum (IETM). Global temperatures rose by up to 8oC over only ~10kyr and a massive perturbation of the global carbon cycle occurred; creating a negative carbon isotopic (~-4% δ13C) excursion in sedimentary records. This interval has relevance to study of future climate change and its influence on geohazards including submarine landslides and turbidity currents. We analyse the recurrence frequency of turbidity currents, potentially initiated from large-volume slope failures. The study focuses on two sedimentary intervals that straddle the IETM and we discuss implications for turbidity current triggering. We present the results of statistical analyses (regression, generalised linear model, and proportional hazards model) for extensive turbidite records from an outcrop at Zumaia in NE Spain (N=285; 54.0 to 56.5 Ma) and based on ODP site 1068 on the Iberian Margin (N=1571; 48.2 to 67.6 Ma). The sedimentary sequences provide clear differentiation between hemipelagic and turbiditic mud with only negligible evidence of erosion. We infer dates for turbidites by converting hemipelagic bed thicknesses to time using interval-averaged accumulation rates. Multi-proxy dating techniques provide good age constraint. The background trend for the Zumaia record shows a near-exponential distribution of turbidite recurrence intervals, while the Iberian Margin shows a log-normal response. This is interpreted to be related to regional time-independence (exponential) and the effects of additive processes (log-normal). We discuss how a log-normal response may actually be generated over geological timescales from multiple shorter periods of random turbidite recurrence. The IETM interval shows a dramatic departure from both these background trends, however. This is marked by prolonged hiatuses (0.1 and 0.6 Myr duration) in turbidity current activity in contrast to the arithmetic mean recurrence, λ, for the full records (λ=0.007 and 0.0125 Myr). This period of inactivity is coincident with a dramatic carbon isotopic excursion (i.e. warmest part of the IETM) and heavily skews statistical analyses for both records. Dramatic global warming appears to exert a strong control on inhibiting turbidity current activity; whereas the effects of sea level change are not shown to be statistically significant. Rapid global warming is often implicated as a potential landslide trigger, due to dissociation of gas hydrates in response to elevated ocean temperatures. Other studies have suggested that intense global warming may actually be attributed to the atmospheric release of gas hydrates following catastrophic failure of large parts of a continental slope. Either way, a greater intensity of landslide and resultant turbidity current activity would be expected during the IETM; however, our findings are to the contrary. We offer some explanations in relation to potential triggers. Our work suggests that previous rapid global warming at the IETM did not trigger more frequent turbidity currents. This has direct relevance to future assessments relating to landslide-triggered tsunami hazard, and breakage of subsea cables by turbidity currents.

MMP-2 as an early synovial biomarker for cranial cruciate ligament disease in dogs.

PubMed

Boland, L; Danger, R; Cabon, Q; Rabillard, M; Brouard, S; Bouvy, B; Gauthier, O

2014-01-01

To measure the activity of matrix metalloproteinases (MMP)-2 and -9 in synovial fluid from the stifle joints of dogs with cranial cruciate ligament (CrCL) rupture and to compare that to values from contralateral stifle joints and dogs with clinically normal stifle joints. Additionally, the C-reactive protein (CRP) levels were also measured. Fourteen large breed dogs with unilateral CrCL rupture and 11 large breed normal dogs were included in this prospective clinical study. Synovial fluid was collected from CrCL-ruptured stifle joints, contralateral clinically normal stifle joints of the same dogs, and stifle joints of normal dogs. Serum was also collected. Synovial fluid activities of MMP-2 and MMP-9 and serum CRP level were measured. The MMP-2 activity in synovial fluid was significantly higher in CrCL-ruptured joints compared to contralateral joints and to stifles from normal dogs. There was no significant difference in activity of MMP-2 in contralateral joints of CrCL-ruptured dogs compared to normal dogs. Both serum CRP level and MMP-9 activity did not differ significantly between the studied conditions. It was confirmed that MMP-2 activity is significantly related to CrCL rupture, but there was a failure to demonstrate any significant increase in the contralateral joints compared to the stifle joints of normal dogs. The MMP-2 involvement in progressing CrCL disease still has to be defined.

Estimating background-subtracted fluorescence transients in calcium imaging experiments: a quantitative approach.

PubMed

Joucla, Sébastien; Franconville, Romain; Pippow, Andreas; Kloppenburg, Peter; Pouzat, Christophe

2013-08-01

Calcium imaging has become a routine technique in neuroscience for subcellular to network level investigations. The fast progresses in the development of new indicators and imaging techniques call for dedicated reliable analysis methods. In particular, efficient and quantitative background fluorescence subtraction routines would be beneficial to most of the calcium imaging research field. A background-subtracted fluorescence transients estimation method that does not require any independent background measurement is therefore developed. This method is based on a fluorescence model fitted to single-trial data using a classical nonlinear regression approach. The model includes an appropriate probabilistic description of the acquisition system's noise leading to accurate confidence intervals on all quantities of interest (background fluorescence, normalized background-subtracted fluorescence time course) when background fluorescence is homogeneous. An automatic procedure detecting background inhomogeneities inside the region of interest is also developed and is shown to be efficient on simulated data. The implementation and performances of the proposed method on experimental recordings from the mouse hypothalamus are presented in details. This method, which applies to both single-cell and bulk-stained tissues recordings, should help improving the statistical comparison of fluorescence calcium signals between experiments and studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Differential activation of catalase expression and activity by PPAR agonists: Implications for astrocyte protection in anti-glioma therapy☆

PubMed Central

Khoo, Nicholas K.H.; Hebbar, Sachin; Zhao, Weiling; Moore, Steven A.; Domann, Frederick E.; Robbins, Mike E.

2013-01-01

Glioma survival is dismal, in part, due to an imbalance in antioxidant expression and activity. Peroxisome proliferator-activated receptor (PPAR) agonists have antineoplastic properties which present new redox-dependent targets for glioma anticancer therapies. Herein, we demonstrate that treatment of primary cultures of normal rat astrocytes with PPAR agonists increased the expression of catalase mRNA protein, and enzymatic activity. In contrast, these same agonists had no effect on catalase expression and activity in malignant rat glioma cells. The increase in steady-state catalase mRNA observed in normal rat astrocytes was due, in part, to de novo mRNA synthesis as opposed to increased catalase mRNA stability. Moreover, pioglitazone-mediated induction of catalase activity in normal rat astrocytes was completely blocked by transfection with a PPARγ-dominant negative plasmid. These data suggest that defects in PPAR-mediated signaling and gene expression may represent a block to normal catalase expression and induction in malignant glioma. The ability of PPAR agonists to differentially increase catalase expression and activity in normal astrocytes but not glioma cells suggests that these compounds might represent novel adjuvant therapeutic agents for the treatment of gliomas. PMID:24024139

[Psychosomatic approach to encopresis].

PubMed

Boige, N; Missonnier, S; Bellaïche, M; Foucaud, P

1999-12-01

Encopresis most often results from functional constipation and a behaviour disorder characterised by retention of faeces. Rarely it is a passive or active expulsion of normal faeces. It indicates a failure in the education of sphincter control, often with a preferential development of autoerotic versus relational investments. A depressive component is frequent. We propose a bidisciplinary approach with a somatic and psychological evaluation of the encopretic child from the first visit. The physical examination assesses constipation and stercoral stasis. Associated psychopathological symptoms or a pathogenic psychosocial situation must be sought. The therapeutic means must be directed towards the different etiologic features. Explanations of the physiopathology of the symptom and discussion with the child and the parents on the origin of the dysfunction must be accomplished first. A medical treatment of the constipation is generally indicated. Psychotherapy is initiated according to the background and associated psychopathological symptoms.

The Chandra Deep Field-North Survey and the cosmic X-ray background.

PubMed

Brandt, W Nielsen; Alexander, David M; Bauer, Franz E; Hornschemeier, Ann E

2002-09-15

Chandra has performed a 1.4 Ms survey centred on the Hubble Deep Field-North (HDF-N), probing the X-ray Universe 55-550 times deeper than was possible with pre-Chandra missions. We describe the detected point and extended X-ray sources and discuss their overall multi-wavelength (optical, infrared, submillimetre and radio) properties. Special attention is paid to the HDF-N X-ray sources, luminous infrared starburst galaxies, optically faint X-ray sources and high-to-extreme redshift active galactic nuclei. We also describe how stacking analyses have been used to probe the average X-ray-emission properties of normal and starburst galaxies at cosmologically interesting distances. Finally, we discuss plans to extend the survey and argue that a 5-10 Ms Chandra survey would lay key groundwork for future missions such as XEUS and Generation-X.

Early bronchopulmonary involvement in Crohn disease: a case report

PubMed Central

Valletta, Enrico; Bertini, Marina; Sette, Luciano; Braggion, Cesare; Pradal, Ugo; Zannoni, Marina

2001-01-01

Background Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease. Case presentation A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation. Conclusions Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD. PMID:11734067

Individual Differences in Typical Reappraisal Use Predict Amygdala and Prefrontal Responses

PubMed Central

Drabant, Emily M.; McRae, Kateri; Manuck, Stephen B.; Hariri, Ahmad R.; Gross, James J.

2010-01-01

Background Participants who are instructed to use reappraisal to downregulate negative emotion show decreased amygdala responses and increased prefrontal responses. However, it is not known whether individual differences in the tendency to use reappraisal manifests in similar neural responses when individuals are spontaneously confronted with negative situations. Such spontaneous emotion regulation might play an important role in normal and pathological responses to the emotional challenges of everyday life. Methods Fifty-six healthy women completed a blood oxygenation-level dependent functional magnetic resonance imaging challenge paradigm involving the perceptual processing of emotionally negative facial expressions. Participants also completed measures of typical emotion regulation use, trait anxiety, and neuroticism. Results Greater use of reappraisal in everyday life was related to decreased amygdala activity and increased prefrontal and parietal activity during the processing of negative emotional facial expressions. These associations were not attributable to variation in trait anxiety, neuroticism, or the use of another common form of emotion regulation, namely suppression. Conclusions These findings suggest that, like instructed reappraisal, individual differences in reappraisal use are associated with decreased activation in ventral emotion generative regions and increased activation in prefrontal control regions in response to negative stimuli. Such individual differences in emotion regulation might predict successful coping with emotional challenges as well as the onset of affective disorders. PMID:18930182

77 FR 10508 - Agency Information Collection Activities; Proposed Collection; Comment Request; Background Checks...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... Activities; Proposed Collection; Comment Request; Background Checks for Contractor Employees (Renewal) AGENCY... the electronic docket, go to www.regulations.gov . Title: Background Checks for Contractor Employees... consolidated in 40 CFR part 9. Abstract: The EPA uses contractors to perform services throughout the nation...

Activation of Background Knowledge for Inference Making: Effects on Reading Comprehension

ERIC Educational Resources Information Center

Elbro, Carsten; Buch-Iversen, Ida

2013-01-01

Failure to "activate" relevant, existing background knowledge may be a cause of poor reading comprehension. This failure may cause particular problems with inferences that depend heavily on prior knowledge. Conversely, teaching how to use background knowledge in the context of gap-filling inferences could improve reading comprehension in…

The Faster, Better, Cheaper Approach to Space Missions: An Engineering Management Assessment

NASA Technical Reports Server (NTRS)

Hamaker, Joe

2000-01-01

This paper describes, in viewgraph form, the faster, better, cheaper approach to space missions. The topics include: 1) What drives "Faster, Better, Cheaper"? 2) Why Space Programs are Costly; 3) Background; 4) Aerospace Project Management (Old Culture); 5) Aerospace Project Management (New Culture); 6) Scope of Analysis Limited to Engineering Management Culture; 7) Qualitative Analysis; 8) Some Basic Principles of the New Culture; 9) Cause and Effect; 10) "New Ways of Doing Business" Survey Results; 11) Quantitative Analysis; 12) Recent Space System Cost Trends; 13) Spacecraft Dry Weight Trend; 14) Complexity Factor Trends; 15) Cost Normalization; 16) Cost Normalization Algorithm; 17) Unnormalized Cost vs. Normalized Cost; and 18) Concluding Observations.

Background considerations in the analysis of PIXE spectra by Artificial Neural Systems.

NASA Astrophysics Data System (ADS)

Correa, R.; Morales, J. R.; Requena, I.; Miranda, J.; Barrera, V. A.

2016-05-01

In order to study the importance of background in PIXE spectra to determine elemental concentrations in atmospheric aerosols using artificial neural systems ANS, two independently trained ANS were constructed, one which considered as input the net number of counts in the peak, and another which included the background. In the training and validation phases thirty eight spectra of aerosols collected in Santiago, Chile, were used. In both cases the elemental concentration values were similar. This fact was due to the intrinsic characteristic of ANS operating with normalized values of the net and total number of counts under the peaks, something that was verified in the analysis of 172 spectra obtained from aerosols collected in Mexico city. Therefore, networks operating under the mode which include background can reduce time and cost when dealing with large number of samples.

Characterization of background concentrations of contaminants using a mixture of normal distributions.

PubMed

Qian, Song S; Lyons, Regan E

2006-10-01

We present a Bayesian approach for characterizing background contaminant concentration distributions using data from sites that may have been contaminated. Our method, focused on estimation, resolves several technical problems of the existing methods sanctioned by the U.S. Environmental Protection Agency (USEPA) (a hypothesis testing based method), resulting in a simple and quick procedure for estimating background contaminant concentrations. The proposed Bayesian method is applied to two data sets from a federal facility regulated under the Resource Conservation and Restoration Act. The results are compared to background distributions identified using existing methods recommended by the USEPA. The two data sets represent low and moderate levels of censorship in the data. Although an unbiased estimator is elusive, we show that the proposed Bayesian estimation method will have a smaller bias than the EPA recommended method.

78 FR 63242 - Proposed Template Safe Harbor Agreement for the Solano County Water Agency in Yolo and Solano...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-23

... to view the document at the above address during normal business hours (see ADDRESSES). Background... listed species to their property, to increase the numbers or distribution of listed species already on...

78 FR 69131 - Importer of Controlled Substances; Notice of Registration; Catalent CTS, LLC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-18

... treatment of wounds which contains trace amounts of the controlled substances normally found in poppy straw... company's background and history. Therefore, pursuant to 21 U.S.C. 952(a) and 958(a), and in accordance...

Polarimetric Thermal Imaging

DTIC Science & Technology

2007-03-01

front of a large area blackbody as background. The viewing angle , defined as the angle between surface normal and camera line of sight, was varied by...and polarization angle were derived from the Stokes parameters. The dependence of these polarization characteristics on viewing angle was investigated

Responses of a constructed plant community to simulated glyphosate and dicamba drift

EPA Science Inventory

Background/Questions/Methods As part of its regulation of pesticides, the US Environmental Protection Agency must consider environmental risks, including impacts to nontarget plants exposed to pesticide drift. Normally these risk assessments consider impacts to individual spec...

An Apparatus for Photochemical Studies.

ERIC Educational Resources Information Center

Winter, M. J.; Winter, P. V.

1984-01-01

Describes an apparatus developed for photochemical studies, particularly those involving the fluorescence of halogenated acetones. The apparatus is constructed from equipment normally found in a moderately sized physical chemical laboratory. Also provides background information on some aspects of the photophysics of halogenated propanones. (JN)

THE INFECTIVITY OF CRYPTOSPORIDIUM PARVUM IN HEALTHY VOLUNTEERS

EPA Science Inventory

Background. Small numbers of Cryptosporidium parvum oocysts can contaminate even treated drinking water, and ingestion of oocysts can cause diarrheal disease in normal as well as immunocompromised hosts. Since the number of organisms necessary to cause infection in humans is unkn...

Masticatory Muscle Sleep Background EMG Activity is Elevated in Myofascial TMD Patients

PubMed Central

Raphael, Karen G.; Janal, Malvin N.; Sirois, David A.; Dubrovsky, Boris; Wigren, Pia E.; Klausner, Jack J.; Krieger, Ana C.; Lavigne, Gilles J.

2013-01-01

Despite theoretical speculation and strong clinical belief, recent research using laboratory polysomnographic (PSG) recording has provided new evidence that frequency of sleep bruxism (SB) masseter muscle events, including grinding or clenching of the teeth during sleep, is not increased for women with chronic myofascial temporomandibular disorder (TMD). The current case-control study compares a large sample of women suffering from chronic myofascial TMD (n=124) with a demographically matched control group without TMD (n=46) on sleep background electromyography (EMG) during a laboratory PSG study. Background EMG activity was measured as EMG root mean square (RMS) from the right masseter muscle after lights out. Sleep background EMG activity was defined as EMG RMS remaining after activity attributable to SB, other orofacial activity, other oromotor activity and movement artifacts were removed. Results indicated that median background EMG during these non SB-event periods was significantly higher (p<.01) for women with myofascial TMD (median=3.31 μV and mean=4.98 μV) than for control women (median=2.83 μV and mean=3.88 μV) with median activity in 72% of cases exceeding control activity. Moreover, for TMD cases, background EMG was positively associated and SB event-related EMG was negatively associated with pain intensity ratings (0–10 numerical scale) on post sleep waking. These data provide the foundation for a new focus on small, but persistent, elevations in sleep EMG activity over the course of the night as a mechanism of pain induction or maintenance. PMID:24237356

Activated Prothrombin Complex Concentrate Versus 4-Factor Prothrombin Complex Concentrate for Vitamin K-Antagonist Reversal.

PubMed

Rowe, A Shaun; Dietrich, Scott K; Phillips, John W; Foster, Kaci E; Canter, Joshua R

2018-06-01

To compare the international normalized ratio normalization efficacy of activated prothrombin complex concentrates and 4-factor prothrombin complex concentrates and to evaluate the thrombotic complications in patients treated with these products for warfarin-associated hemorrhage. Retrospective, Multicenter Cohort. Large, Community, Teaching Hospital. Patients greater than 18 years old and received either activated prothrombin complex concentrate or 4-factor prothrombin complex concentrate for the treatment of warfarin-associated hemorrhage. We excluded those patients who received either agent for an indication other than warfarin-associated hemorrhage, pregnant, had a baseline international normalized ratio of less than 2, received a massive transfusion as defined by hospital protocol, received plasma for treatment of warfarin-associated hemorrhage, or were treated for an acute warfarin ingestion. Patients in the activated prothrombin complex concentrate group (enrolled from one hospital) with an international normalized ratio of less than 5 received 500 IU and those with an international normalized ratio greater than 5 received 1,000 IU. Patients in the 4-factor prothrombin complex concentrate (enrolled from a separate hospital) group received the Food and Drug Administration approved dosing algorithm. A total of 158 patients were included in the final analysis (activated prothrombin complex concentrate = 118; 4-factor prothrombin complex concentrate = 40). Those in the 4-factor prothrombin complex concentrate group had a higher pretreatment international normalized ratio (2.7 ± 1.8 vs 3.5 ± 2.9; p = 0.0164). However, the posttreatment international normalized ratio was similar between the groups. In addition, even when controlling for differences in the pretreatment international normalized ratio, there was no difference in the ability to achieve a posttreatment international normalized ratio of less than 1.4 (odds ratio, 0.753 [95% CI, 0.637-0.890]; p = 0.0009). Those in the activated prothrombin complex concentrate group did have higher odds of achieving a posttreatment international normalized ratio of less than 1.2 (odds ratio, 3.23 [95% CI, 1.34-7.81]; p = 0.0088). There was only one posttreatment thrombotic complication reported. A low, fixed dose of activated prothrombin complex concentrate was as effective as standard dose 4-factor prothrombin complex concentrate for normalization of international normalized ratio. In addition, we did not see an increase in thrombotic events.

CO2 lidar backscatter experiment

NASA Technical Reports Server (NTRS)

Jarzembski, Maurice A.; Rothermel, Jeffry; Bowdle, David A.; Srivastava, Vandana; Cutten, Dean; Mccaul, Eugene W., Jr.

1993-01-01

The Aerosol/Lidar Science Group of the Remote Sensing Branch engages in experimental and theoretical studies of atmospheric aerosol scattering and atmospheric dynamics, emphasizing Doppler lidar as a primary tool. Activities include field and laboratory measurement and analysis efforts by in-house personnel, coordinated with similar efforts by university and government institutional researchers. The primary focus of activities related to understanding aerosol scattering is the GLObal Backscatter Experiment (GLOBE) program. GLOBE was initiated by NASA in 1986 to support the engineering design, performance simulation, and science planning for the prospective NASA Laser Atmospheric Wind Sounder (LAWS). The most important GLOBE scientific result has been identified of a background aerosol mode with a surprisingly uniform backscatter mixing ratio (backscatter normalized by air density) throughout a deep tropospheric layer. The backscatter magnitude of the background mode evident from the MSFC CW lidar measurements is remarkably similar to that evident from ground-based backscatter profile climatologies obtained by JPL in Pasadena CA, NOAA/WPL in Boulder CO, and by the Royal Signals and Radar Establishment in the United Kingdom. Similar values for the background mode have been inferred from the conversion of in situ aerosol microphysical measurements to backscatter using Mie theory. Little seasonal or hemispheric variation is evident in the survey mission data, as opposed to large variation for clouds, aerosol plums, and the marine boundary layer. Additional features include: localized aerosol residues from dissipated clouds, occasional regions having mass concentrations of nanograms per cubic meter and very low backscatter, and aerosol plumes extending thousands of kilometers and several kilometers deep. Preliminary comparison with meteorological observations thus far indicate correlation between backscatter and water vapor under high humidity conditions. Limited intercomparisons with the Stratospheric Aerosol and Gas Experiment (SAGE) limb extinction sounder shows differences in the troposphere, however, it should be noted that in general SAGE measurements have not yet been validated in the troposphere.

Associations of Baroreflex Sensitivity, Heart Rate Variability, and Initial Orthostatic Hypotension with Prenatal and Recent Postnatal Methylmercury Exposure in the Seychelles Child Development Study at Age 19 Years

PubMed Central

Périard, Daniel; Beqiraj, Bujar; Hayoz, Daniel; Viswanathan, Bharathi; Evans, Katie; Thurston, Sally W.; Davidson, Philip W.; Myers, Gary J.; Bovet, Pascal

2015-01-01

Background: A few studies have suggested an association between prenatal exposure to methylmercury and decreased heart rate variability (HRV) related to autonomic heart function, but no study has examined this association using baroreflex sensitivity (BRS). In this study we assessed the distribution of BRS and immediate orthostatic hypotension (IOH) in young Seychellois adults and their associations with exposure to prenatal and recent postnatal methylmercury. Methods: Subjects in theSeychelles Child Development Study (SCDS) main cohort were evaluated at age 19 years. Non-invasive beat-to-beat blood pressure (BP) monitoring (Finapres, Ohmeda) was performed at rest and during active standing in 95 consecutive subjects. Recent postnatal mercury exposure was measured in subjects’ hair at the age of 19 years and prenatal exposure in maternal hair grown during pregnancy. BRS was estimated by sequence analysis to identify spontaneous ascending and descending BP ramps. HRV was estimated by the following markers: PNN50 (relative numbers of normal-to-normal intervals which are shorter by more than 50 ms than the immediately following normal-to-normal intervals); rMSSD (root mean of the squared sum of successive interval differences); LF/HF (low frequency/high frequency component ratio); ratio of the mean expiratory/inspiratory RR intervals (EI ratio); and the ratio between the longest RR interval 30 s after active standing and the shortest RR interval at 15 s (Max30/Min15). IOH was estimated by the deepest BP fall within the first 15 s after active standing up. Results: Prenatal MeHg exposures were similar in boys and girls (6.7 ± 4.3, 6.7 ± 3.8 ng/g) but recent postnatal mercury levels were higher in males than females (11.2 ± 5.8 vs 7.9 ± 4.3 ng/g, p = 0.003). Markers of autonomic heart rate control were within the normal range (BRS: 24.8 ± 7 ms/mm Hg, PNN50: 24.9 ± 6.8%, rMSSD: 68 ± 22, LF/HF: 0.61 ± 0.28) in both sexes. After standing, 51.4% of subjects had a transient systolic BP drop >40 mm Hg, but only 5.3% reported dizziness or had syncope. Prenatal and recent postnatal MeHg levels, overall, were not associated with BRS, E/I ratio, PNN50, rMSSD, LF/HF ratio, Max30/Min15 ratio, and IOH. Conclusions: This study provides no support for the hypothesis that prenatal or recent postnatal MeHg exposure from fish consumption is associated with impaired autonomic heart rate control. PMID:25807149

Evaluation of hypoglycemic and anti-hyperglycemic potential of Tridax procumbens (Linn.)

PubMed Central

2009-01-01

Background Diabetes is a metabolic disorder affecting carbohydrate, fat and protein metabolism. Tridax procumbens Linn. (Family-Asteraceae; common name-Dhaman grass) is common herb found in India. Traditionally, the tribal inhabitants of Udaipur district in Rajasthan (India) uses the leaf powder (along with other herb) orally to treat diabetes. There is a need to evaluate extracts of this plant in order to provide scientific proof for it's application in traditional medicine system. Methods Extraction of whole plant of T. procumbens using 50%methanol. The extract was tested for acute and sub-chronic anti-hyperglycemic activity in alloxan induced diabetic rats and for acute toxicity test among normal rats. Observations on body weight as well as on the oral glucose tolerance levels were also recorded. Results Oral administration of acute and sub chronic doses (250 and 500 mg/kg b.wt.) of T. procumbens extract showed a significant (p < 0.05) reduction in fasting blood glucose levels in diabetic rats, however the decline in blood sugar levels in normal rats was not observed. In acute study the maximum percent blood glucose reduction (68.26% at 250 mg/kg and 71.03% at 500 mg/kg body weight) in diabetic rats was observed at 6 h. The anti-hyperglycemic effects were not dependent of dose and the OGTT and Body weight supported the antihyperglycemic action of the drug. The results of anti-diabetic effect of T. procumbens were compared with the reference standard drug Glibenclamide (10 mg/kg b.wt.). Conclusion These test results support traditional medicinal use of, T. procumbens for the treatment of diabetes mellitus with corrections in body weight and oral glucose tolerance and no visible signs or symptoms of toxicity in normal rats indicating a high margin of safety. These results warrant follow-up through bioassay-directed isolation of the active principles. PMID:19943967

MicroRNA-145 Inhibits Cell Migration and Invasion and Regulates Epithelial-Mesenchymal Transition (EMT) by Targeting Connective Tissue Growth Factor (CTGF) in Esophageal Squamous Cell Carcinoma.

PubMed

Han, Qiang; Zhang, Hua-Yong; Zhong, Bei-Long; Wang, Xiao-Jing; Zhang, Bing; Chen, Hua

2016-10-23

BACKGROUND This study investigated the mechanism of miR-145 in targeting connective tissue growth factor (CTGF), which affects the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of ESCC cells. MATERIAL AND METHODS A total of 50 ESCC tissues and their corresponding normal adjacent esophageal tissue samples were collected. Then, miR-145 expression in both ESCC clinical specimens and cell lines was detected using quantitative real-time PCR. CTGF protein was detected using immunohistochemistry. Dual luciferase reporter gene assay was employed to assess the effect of miR-145 on the 3'UTR luciferase activity of CTGF. Eca109 cells were transfected with miR-145 mimics and CTGF siRNA, respectively, and changes in cellular proliferation, migration, and invasion were detected via MTT assay, wound-healing assay, and Transwell assay, respectively. Western blotting assay was used to detect the expression of marker genes related to EMT. RESULTS MiR-145 was significantly down-regulated in ESCC tissues and cell lines compared with normal tissues and cell lines (P<0.05). We found significantly more positively expressed CTGF protein in ESCC tissues was than in normal adjacent esophageal tissues (P<0.01). Dual luciferase reporter gene assay showed that miR-145 can specifically bind with the 3'UTR of CTGF and significantly inhibit the luciferase activity by 55% (P<0.01). Up-regulation of miR-145 or down-regulation of CTGF can suppress the proliferation, migration, invasion, and EMT process of ESCC cells. CONCLUSIONS MiR-145 was significantly down-regulated in ESCC tissues and cell lines, while the protein expression of CTGF exhibited the opposite trend. MiR-145 inhibited the proliferation, migration, invasiveness, and the EMT process of ESCC cells through targeted regulation of CTGF expression.

Associations between food insecurity and healthy behaviors among Korean adults

PubMed Central

Chun, In-Ae; Park, Jong; Ro, Hee-Kyung; Han, Mi-Ah

2015-01-01

BACKGROUND/OBJECTIVES Food insecurity has been suggested as being negatively associated with healthy behaviors and health status. This study was performed to identify the associations between food insecurity and healthy behaviors among Korean adults. SUBJECTS/METHODS The data used were the 2011 Community Health Survey, cross-sectional representative samples of 253 communities in Korea. Food insecurity was defined as when participants reported that their family sometimes or often did not get enough food to eat in the past year. Healthy behaviors were considered as non-smoking, non-high risk drinking, participation in physical activities, eating a regular breakfast, and maintaining a normal weight. Multiple logistic regression and multinomial logistic regression analyses were used to identify the association between food insecurity and healthy behaviors. RESULTS The prevalence of food insecurity was 4.4% (men 3.9%, women 4.9%). Men with food insecurity had lower odds ratios (ORs) for non-smoking, 0.75 (95% CI: 0.68-0.82), participation in physical activities, 0.82 (95% CI: 0.76-0.90), and eating a regular breakfast, 0.66 (95% CI: 0.59-0.74), whereas they had a higher OR for maintaining a normal weight, 1.19 (95% CI: 1.09-1.30), than men with food security. Women with food insecurity had lower ORs for non-smoking, 0.77 (95% CI: 0.66-0.89), and eating a regular breakfast, 0.79 (95% CI: 0.72-0.88). For men, ORs for obesity were 0.78 (95% CI: 0.70-0.87) for overweight and 0.56 (95% CI: 0.39-0.82) for mild obesity. For women, the OR for moderate obesity was 2.04 (95% CI: 1.14-3.63) as compared with normal weight. CONCLUSIONS Food insecurity has a different impact on healthy behaviors. Provision of coping strategies for food insecurity might be critical to improve healthy behaviors among the population. PMID:26244083

Long-Term Effects of Highly Active Antiretroviral Therapy on CD4+ Cell Evolution among Children and Adolescents Infected with HIV: 5 Years and Counting

PubMed Central

Patel, Kunjal; Hernán, Miguel A.; Williams, Paige L.; Seeger, John D.; McIntosh, Kenneth; Van Dyke, Russell B.; Seage, George R.

2011-01-01

Background Lower percentages of CD4+ T lymphocytes are associated with adverse clinical outcomes among children and adolescents infected with human immunodeficiency virus (HIV). CD4+ lymphocyte percentage generally increases with receipt of highly active antiretroviral therapy (HAART), but long-term follow-up is required to assess whether these increases in CD4+ cell percentage are maintained and whether they lead to normal CD4+ cell percentages in children with severe immunosuppression. Methods The study population included 1236 children and adolescents perinatally infected with HIV who were enrolled in a US-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C) and who were not receiving HAART at study initiation. We estimated the effects of HAART, HAART with protease inhibitors, and HAART with nonnucleoside reverse-transcriptase inhibitors on CD4+ cell percentage, using marginal structural models to account for confounding by severity. Results Initiation of any type of HAART increased CD4+ cell percentage by 2.34% (95% confidence interval, 1.35%–3.33%) in the first year, relative to noninitiation of HAART. The substantial increases in CD4+ cell percentage observed after the first year of experience with these combination therapies were followed by relatively smaller increases that continued for 5 years after initiation. Although larger increases in CD4+ cell percentage were observed among children with a greater degree of immunosuppression at baseline, the mean CD4+ cell percentage after 5 years of HAART did not reach normal levels. Conclusions Our study supports the initiation of HAART in children before severe immunosuppression occurs for long-term maintenance of normal CD4+ cell percentages. This beneficial result must be weighed against the evidence of potential adverse events associated with the prolonged use of such therapy. PMID:18426371

The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abbasi, Rashda; Efferth, Thomas; Kuhmann, Christine

2012-03-15

Targeting synthetic lethality in DNA repair pathways has become a promising anti-cancer strategy. However little is known about such interactions with regard to the nucleotide excision repair (NER) pathway. Therefore, cell lines with a defect in the NER genes ERCC6 or XPC and their normal counterparts were screened with 53 chemically defined phytochemicals isolated from plants used in traditional Chinese medicine for differential cytotoxic effects. The screening revealed 12 drugs that killed NER-deficient cells more efficiently than proficient cells. Five drugs were further analyzed for IC{sub 50} values, effects on cell cycle distribution, and induction of DNA damage. Ascaridol wasmore » the most effective compound with a difference of > 1000-fold in resistance between normal and NER-deficient cells (IC{sub 50} values for cells with deficiency in ERCC6: 0.15 μM, XPC: 0.18 μM, and normal cells: > 180 μM). NER-deficiency combined with ascaridol treatment led to G2/M-phase arrest, an increased percentage of subG1 cells, and a substantially higher DNA damage induction. These results were confirmed in a second set of NER-deficient and -proficient cell lines with isogenic background. Finally, ascaridol was characterized for its ability to generate oxidative DNA damage. The drug led to a dose-dependent increase in intracellular levels of reactive oxygen species at cytotoxic concentrations, but only NER-deficient cells showed a strongly induced amount of 8-oxodG sites. In summary, ascaridol is a cytotoxic and DNA-damaging compound which generates intracellular reactive oxidative intermediates and which selectively affects NER-deficient cells. This could provide a new therapeutic option to treat cancer cells with mutations in NER genes. -- Highlights: ► Thousand-fold higher Ascaridol activity in NER-deficient versus proficient cells. ► Impaired repair of Ascaridol-induced oxidative DNA damage in NER-deficient cells. ► Selective activity of Ascaridol opens new therapy options in NER-deficient tumors.« less

Background radioactivity in sediments near Los Alamos, New Mexico.

PubMed

McLin, Stephen G

2004-07-26

River and reservoir sediments have been collected annually by Los Alamos National Laboratory since 1974 and 1979, respectively. These background samples are collected from five river stations and four reservoirs located throughout northern New Mexico and southern Colorado. Analyses include 3H, 90Sr, 137Cs, total U, 238Pu, 239,240Pu, 241Am, gross alpha, gross beta, and gross gamma radioactivity. Surprisingly, there are no federal or state regulatory standards in the USA that specify how to compute background radioactivity values on sediments. Hence, the sample median (or 0.50 quantile) is proposed for this background because it reflects central data tendency and is distribution-free. Estimates for the upper limit of background radioactivity on river and reservoir sediments are made for sampled analytes using the 0.95 quantile (two-tail). These analyses also show that seven of ten analytes from reservoir sediments are normally distributed, or are normally distributed after a logarithmic or square root transformation. However, only three of ten analytes from river sediments are similarly distributed. In addition, isotope ratios for 137Cs/238Pu, 137Cs/239,240Pu, and 239,240Pu/238Pu from reservoir sediments are independent of clay content, total organic carbon/specific surface area (TOC/SSA) and cation exchange capacity/specific surface area (CEC/SSA) ratios. These TOC/SSA and CEC/SSA ratios reflect sediment organic carbon and surface charge densities that are associated with radionuclide absorption, adsorption, and ion exchange reactions on clay mineral structures. These latter ratio values greatly exceed the availability of background radionuclides in the environment, and insure that measured background levels are a maximum. Since finer-grained reservoir sediments contain larger clay-sized fractions compared to coarser river sediments, they show higher background levels for most analytes. Furthermore, radioactivity values on reservoir sediments have remained relatively constant since the early 1980s. These results suggest that clay contents in terrestrial sediments are often more important at concentrating background radionuclides than many other environmental factors, including geology, climate and vegetation. Hence, reservoirs and floodplains represent ideal radionuclide sampling locations because fine-grained materials are more easily trapped here. Ultimately, most of these differences still reflect spatial and temporal variability originating from global atmospheric nuclear weapons testing and disintegration of nuclear-powered satellites upon atmospheric reentry. Copyright 2004 Elsevier B.V.

Serine 302 Phosphorylation of Mouse Insulin Receptor Substrate 1 (IRS1) Is Dispensable for Normal Insulin Signaling and Feedback Regulation by Hepatic S6 Kinase*

PubMed Central

Copps, Kyle D.; Hançer, Nancy J.; Qiu, Wei; White, Morris F.

2016-01-01

Constitutive activation of the mammalian target of rapamycin complex 1 and S6 kinase (mTORC1→ S6K) attenuates insulin-stimulated Akt activity in certain tumors in part through “feedback” phosphorylation of the upstream insulin receptor substrate 1 (IRS1). However, the significance of this mechanism for regulating insulin sensitivity in normal tissue remains unclear. We investigated the function of Ser-302 in mouse IRS1, the major site of its phosphorylation by S6K in vitro, through genetic knock-in of a serine-to-alanine mutation (A302). Although insulin rapidly stimulated feedback phosphorylation of Ser-302 in mouse liver and muscle, homozygous A302 mice (A/A) and their knock-in controls (S/S) exhibited similar glucose homeostasis and muscle insulin signaling. Furthermore, both A302 and control primary hepatocytes from which Irs2 was deleted showed marked inhibition of insulin-stimulated IRS1 tyrosine phosphorylation and PI3K binding after emetine treatment to raise intracellular amino acids and activate mTORC1 → S6K signaling. To specifically activate mTORC1 in mouse tissue, we deleted hepatic Tsc1 using Cre adenovirus. Although it moderately decreased IRS1/PI3K association and Akt phosphorylation in liver, Tsc1 deletion failed to cause glucose intolerance or promote hyperinsulinemia in mixed background A/A or S/S mice. Moreover, Tsc1 deletion failed to stimulate phospho-Ser-302 or other putative S6K sites within IRS1, whereas ribosomal S6 protein was constitutively phosphorylated. Following acute Tsc1 deletion from hepatocytes, Akt phosphorylation, but not IRS1/PI3K association, was rapidly restored by treatment with the mTORC1 inhibitor rapamycin. Thus, within the hepatic compartment, mTORC1 → S6K signaling regulates Akt largely through IRS-independent means with little effect upon physiologic insulin sensitivity. PMID:26846849

Imaging of adrenal incidentalomas with PET using (11)C-metomidate and (18)F-FDG.

PubMed

Minn, Heikki; Salonen, Anna; Friberg, Johan; Roivainen, Anne; Viljanen, Tapio; Långsjö, Jaakko; Salmi, Jorma; Välimäki, Matti; Någren, Kjell; Nuutila, Pirjo

2004-06-01

Our aim was to evaluate the use of PET with (11)C-metomidate and (18)F-FDG for the diagnosis of adrenal incidentalomas. Twenty-one patients underwent hormonal screening before dynamic imaging of the upper abdomen with (11)C-metomidate, and for 19 of these 21 patients, static (18)F-FDG imaging followed. Uptake of (11)C-metomidate and (18)F-FDG in incidentalomas was quantified and correlated with the hormonal work-up and the mass size on CT (median, 2.5 cm; range, 2-10 cm). The final diagnoses were hormonally active adenoma (n = 7), nonsecretory adenoma (n = 5), adrenocortical carcinoma (n = 1), pheochromocytoma (n = 2), benign noncortical tumor (n = 2), normal adrenal (n = 1), and malignant noncortical tumor (n = 3). Diagnosis was established at surgery (n = 9), percutaneous biopsy (n = 4), or follow-up (n = 8). The highest uptake of (11)C-metomidate, expressed as standardized uptake value (SUV), was found in adrenocortical carcinoma (SUV = 28.0), followed by active adenomas (median SUV = 12.7), nonsecretory adenomas (median SUV = 12.2), and noncortical tumors (median SUV = 5.7). Patients with adenomas had significantly higher tumor-to-normal-adrenal (11)C-metomidate SUV ratios than did patients with noncortical tumors. (18)F-FDG detected 2 of 3 noncortical malignancies but failed to detect adrenal metastases from renal cell carcinoma. All inactive and most active adenomas were difficult to detect with (18)F-FDG against background activity, whereas both pheochromocytomas and adrenocortical carcinoma showed slightly increased uptake of (18)F-FDG. There was no correlation between uptake of (11)C-metomidate or (18)F-FDG and mass size. (11)C-Metomidate is a promising PET tracer to identify incidentalomas of adrenocortical origin. (18)F-FDG should be reserved for patients with a moderate to high likelihood of neoplastic disease.

Low-intensity and moderate exercise training improves autonomic nervous system activity imbalanced by postnatal early overfeeding in rats

PubMed Central

2014-01-01

Background Postnatal early overfeeding and physical inactivity are serious risk factors for obesity. Physical activity enhances energy expenditure and consumes fat stocks, thereby decreasing body weight (bw). This study aimed to examine whether low-intensity and moderate exercise training in different post-weaning stages of life is capable of modulating the autonomic nervous system (ANS) activity and inhibiting perinatal overfeeding-induced obesity in rats. Methods The obesity-promoting regimen was begun two days after birth when the litter size was adjusted to 3 pups (small litter, SL) or to 9 pups (normal litter, NL). The rats were organized into exercised groups as follows: from weaning until 90-day-old, from weaning until 50-day-old, or from 60- until 90-days-old. All experimental procedures were performed just one day after the exercise training protocol. Results The SL-no-exercised (SL-N-EXE) group exhibited excess weight and increased fat accumulation. We also observed fasting hyperglycemia and glucose intolerance in these rats. In addition, the SL-N-EXE group exhibited an increase in the vagus nerve firing rate, whereas the firing of the greater splanchnic nerve was not altered. Independent of the timing of exercise and the age of the rats, exercise training was able to significantly blocks obesity onset in the SL rats; even SL animals whose exercise training was stopped at the end of puberty, exhibited resistance to obesity progression. Fasting glycemia was maintained normal in all SL rats that underwent the exercise training, independent of the period. These results demonstrate that moderate exercise, regardless of the time of onset, is capable on improve the vagus nerves imbalanced tonus and blocks the onset of early overfeeding-induced obesity. Conclusions Low-intensity and moderate exercise training can promote the maintenance of glucose homeostasis, reduces the large fat pad stores associated to improvement of the ANS activity in adult rats that were obesity-programmed by early overfeeding. PMID:24914402

Composition and cytotoxic activity of essential oils from Xylopia aethiopica (Dunal) A. Rich, Xylopia parviflora (A. Rich) Benth.) and Monodora myristica (Gaertn) growing in Chad and Cameroon

PubMed Central

2014-01-01

Background Cancer has become a global public health problem and the search for new control measures is urgent. Investigation of plant products such as essential oils from Monodora myristica, Xylopia aethiopica and Xylopia parviflora might lead to new anticancer therapy. In this study, we have investigated the antineoplastic activity of essential oils from fruits of these plants growing in Chad and Cameroon. Methods The essential oils obtained by hydrodistillation of fruits of Monodora myristica, Xylopia aethiopica and Xylopia parviflora collected in Chad and Cameroon were analyzed by GC-FID and GC-MS and investigated for their antiproliferative activity against the breast cancer cell line (MCF7). Results Overall, monoterpenes were mostly found in the six essential oils. Oils from X. aethiopica and X. parviflora from Chad and Cameroon mainly contain β-pinene at 24.6%, 28.2%, 35.7% and 32.9% respectively. Monodora myristica oils from both origins contain mainly α-phellandrene at 52.7% and 67.1% respectively. The plant origin did not significantly influence the chemical composition of oils. The six essential oils exerted cytotoxic activity against cancer (MCF-7) and normal cell lines (ARPE-19), with more pronounced effect on neoplastic cells in the majority of cases. The highest selectivity was obtained with the essential oils of X. parviflora from Chad and Cameroon (5.87 and 5.54) which were more cytotoxic against MCF-7 than against normal cell line (ARPE-19) with IC50 values of 0.155 μL/mL and 0.166 μL/mL respectively. Conclusions Essential oils from fruits of Monodora myristica, Xylopia aethiopica and Xylopia parviflora have shown acceptable antineoplastic potency, and might be investigated further in this regard. PMID:24708588

Differential effects of selective frankincense (Ru Xiang) essential oil versus non-selective sandalwood (Tan Xiang) essential oil on cultured bladder cancer cells: a microarray and bioinformatics study

PubMed Central

2014-01-01

Background Frankincense (Boswellia carterii, known as Ru Xiang in Chinese) and sandalwood (Santalum album, known as Tan Xiang in Chinese) are cancer preventive and therapeutic agents in Chinese medicine. Their biologically active ingredients are usually extracted from frankincense by hydrodistillation and sandalwood by distillation. This study aims to investigate the anti-proliferative and pro-apoptotic activities of frankincense and sandalwood essential oils in cultured human bladder cancer cells. Methods The effects of frankincense (1,400–600 dilutions) (v/v) and sandalwood (16,000–7,000 dilutions) (v/v) essential oils on cell viability were studied in established human bladder cancer J82 cells and immortalized normal human bladder urothelial UROtsa cells using a colorimetric XTT cell viability assay. Genes that responded to essential oil treatments in human bladder cancer J82 cells were identified using the Illumina Expression BeadChip platform and analyzed for enriched functions and pathways. The chemical compositions of the essential oils were determined by gas chromatography–mass spectrometry. Results Human bladder cancer J82 cells were more sensitive to the pro-apoptotic effects of frankincense essential oil than the immortalized normal bladder UROtsa cells. In contrast, sandalwood essential oil exhibited a similar potency in suppressing the viability of both J82 and UROtsa cells. Although frankincense and sandalwood essential oils activated common pathways such as inflammatory interleukins (IL-6 signaling), each essential oil had a unique molecular action on the bladder cancer cells. Heat shock proteins and histone core proteins were activated by frankincense essential oil, whereas negative regulation of protein kinase activity and G protein-coupled receptors were activated by sandalwood essential oil treatment. Conclusion The effects of frankincense and sandalwood essential oils on J82 cells and UROtsa cells involved different mechanisms leading to cancer cell death. While frankincense essential oil elicited selective cancer cell death via NRF-2-mediated oxidative stress, sandalwood essential oil induced non-selective cell death via DNA damage and cell cycle arrest. PMID:25006348

Effect of Sex and Body Mass Index on Children's Physical Activity Intensity during Free Play at an Indoor Soft Play Center: An Exploratory Study.

PubMed

Jones, Michelle A

2017-09-12

Background : Indoor soft play can provide a safe but exciting physical activity opportunity regardless of environmental conditions. Relatively little is known about the quality or quantity of physical activity engaged in by children during indoor free soft play. The aim of this study was to evaluate the contribution indoor free soft play can make in enabling children to meet physical activity guidelines and to evaluate the effects of sex and body mass index category. Methods : Seventy-two boys and girls aged five to 10 years engaged in un-controlled indoor free soft play with a mean duration of 120.7 (27.1) min, during which physical activity was monitored using Actigraph accelerometers. Results : Children spent an average of 61.7 (24.2) min engaging in moderate to vigorous physical activity (MVPA) and 51.4% ( n = 37) achieved the recommended 60 min of MVPA through the single visit to the indoor soft play center. Boys (68.3 (25.7) min) engaged in significantly ( p < 0.05) more MVPA than girls (55.8 (21.4) min). Normal weight (65.7 (23.3) min) children engaged in significantly more MVPA than overweight children (48.0 (18.9) min). Conclusions : Attendance at a soft play indoor center has the potential to support children to engage in sufficient MVPA and overcome environmental factors that can restrict physical activity opportunities.

Effect of Sex and Body Mass Index on Children’s Physical Activity Intensity during Free Play at an Indoor Soft Play Center: An Exploratory Study

PubMed Central

2017-01-01

Background: Indoor soft play can provide a safe but exciting physical activity opportunity regardless of environmental conditions. Relatively little is known about the quality or quantity of physical activity engaged in by children during indoor free soft play. The aim of this study was to evaluate the contribution indoor free soft play can make in enabling children to meet physical activity guidelines and to evaluate the effects of sex and body mass index category. Methods: Seventy-two boys and girls aged five to 10 years engaged in un-controlled indoor free soft play with a mean duration of 120.7 (27.1) min, during which physical activity was monitored using Actigraph accelerometers. Results: Children spent an average of 61.7 (24.2) min engaging in moderate to vigorous physical activity (MVPA) and 51.4% (n = 37) achieved the recommended 60 min of MVPA through the single visit to the indoor soft play center. Boys (68.3 (25.7) min) engaged in significantly (p < 0.05) more MVPA than girls (55.8 (21.4) min). Normal weight (65.7 (23.3) min) children engaged in significantly more MVPA than overweight children (48.0 (18.9) min). Conclusions: Attendance at a soft play indoor center has the potential to support children to engage in sufficient MVPA and overcome environmental factors that can restrict physical activity opportunities. PMID:28895904

PIP3-independent activation of TorC2 and PKB at the cell’s leading edge mediates chemotaxis

PubMed Central

Kamimura, Yoichiro; Xiong, Yuan; Iglesias, Pablo A.; Hoeller, Oliver; Bolourani, Parvin; Devreotes, Peter N.

2008-01-01

Summary Background Studies show that high phosphotidylinositol 3,4,5 tris phosphate (PIP3) promotes cytoskeletal rearrangements and alters cell motility and chemotaxis, possibly through activation of PKBs. However, chemotaxis can still occur in the absence of PIP3 and the identities of the PIP3 independent pathways remain unknown. Results Here, we outline a PIP3-independent pathway linking temporal and spatial activation of PKBs by Tor complex 2 (TorC2) to the chemotactic response. Within seconds of stimulating Dictyostelium cells with chemoattractant, two PKB homologs, PKBA and PKBR1, mediate transient phosphorylation of at least eight proteins, including Talin, PI4P 5-kinase, two RasGefs, and a RhoGap. Surprisingly, all of the substrates are phosphorylated with normal kinetics in cells lacking PI 3-kinase activity. Cells deficient in TorC2 or PKB activity show reduced phosphorylation of the endogenous substrates and are impaired in chemotaxis. The PKBs are activated through phosphorylation of their hydrophobic motifs via TorC2 and subsequent phosphorylation of their activation loops. These chemoattractant-inducible events restricted to the cell’s leading edge even in the absence of PIP3. Activation of TorC2 depends on heterotrimeric G-protein function and intermediate G-proteins, including Ras GTPases. Conclusions The data lead to a model where cytosolic TorC2, encountering locally activated small G-protein(s) at the leading of the cell, becomes activated and phosphorylates PKBs. These in turn phosphorylate a series of signaling and cytoskeletal proteins, thereby regulating directed migration. PMID:18635356

Clinical value of gallium-67 scintigraphy in assessment of disease activity in Wegener's granulomatosis

PubMed Central

Slart, R; Jager, P; Poot, L; Piers, D; Cohen, T; Stegeman, C

2003-01-01

Background: Diagnosis of active pulmonary and paranasal involvement in patients with Wegener's granulomatosis (WG) can be difficult. The diagnostic value of gallium-67 scintigraphy in WG is unclear. Objective: To evaluate the added diagnostic value of gallium-67 scintigraphy in patients with WG with suspected granulomatous inflammation in the paranasal and chest regions. Methods: Retrospectively, the diagnostic contribution of chest and head planar gallium scans in 40 episodes of suspected vasculitis disease activity in 28 patients with WG was evaluated. Scans were grouped into normal or increased uptake for each region. Histological proof or response to treatment was the "gold standard" for the presence of WG activity. Results: WG activity was confirmed in 8 (20%) episodes, with pulmonary locations in three, paranasal in four, and both in one (n=7 patients); all these gallium scans showed increased gallium uptake (sensitivity 100%). Gallium scans were negative for the pulmonary area in 23/36 scans (specificity 64%), and negative for paranasal activity in 13/16 scans (specificity 81%) in episodes without WG activity. Positive predictive value of WG activity for lungs and paranasal region was 24% and 63%, respectively, negative predictive value was 100% for both regions. False positive findings were caused by bacterial or viral infections. Conclusion: Gallium scans are clinically helpful as a negative scan virtually excludes active WG. Gallium scintigraphy of chest and nasal region has a high sensitivity for the detection of disease activity in WG. However, because of positive scans in cases of bacterial or viral infections, specificity was lower. PMID:12810430

Does the fat-but-fit paradigm hold true for all-cause mortality when considering the duration of overweight/obesity? Analyzing the WATCH (Weight, Activity and Time Contributes to Health) paradigm.

PubMed

Dankel, Scott J; Loenneke, Jeremy P; Loprinzi, Paul D

2016-02-01

Physical activity has been shown to attenuate the association between overweight/obesity and mortality. Much less is known, however, on how the duration of overweight/obesity potentially alters this association, which was the purpose of this study. The 1999-2006 NHANES was used and 11,057 adults (ages 36-85) were evaluated. Eight mutually exclusive groups were created: (1) physically active, normal weight now and 10years ago; (2) physically inactive, normal weight now and 10years ago; (3) physically active, overweight/obese now but normal weight 10years ago; (4) physically inactive, normal weight now but overweight/obese 10years ago; (5) physically active, overweight/obese now but normal weight 10years ago; (6) physically inactive, overweight/obese now but normal weight 10years ago; (7) physically active, overweight/obese now and 10years ago; and (8) physically inactive, overweight/obese now and 10years ago. After adjustments, only those individuals that were inactive were at a significantly increased risk for all-cause mortality independent of overweight/obesity status (Groups 2, 4, 6, 8). In alignment with the Exercise is Medicine initiative®, our results provide support for clinicians to perform routine assessments of physical activity, and to further promote physical activity among all individuals regardless of body mass status. Copyright © 2015 Elsevier Inc. All rights reserved.

Enzymatic activity of a subtilisin homolog, Tk-SP, from Thermococcus kodakarensis in detergents and its ability to degrade the abnormal prion protein

PubMed Central

2013-01-01

Background Tk-SP is a member of subtilisin-like serine proteases from a hyperthermophilic archaeon Thermococcus kodakarensis. It has been known that the hyper-stable protease, Tk-SP, could exhibit enzymatic activity even at high temperature and in the presence of chemical denaturants. In this work, the enzymatic activity of Tk-SP was measured in the presence of detergents and EDTA. In addition, we focused to demonstrate that Tk-SP could degrade the abnormal prion protein (PrPSc), a protease-resistant isoform of normal prion protein (PrPC). Results Tk-SP was observed to maintain its proteolytic activity with nonionic surfactants and EDTA at 80°C. We optimized the condition in which Tk-SP functions efficiently, and demonstrated that the enzyme is highly stable in the presence of 0.05% (w/v) nonionic surfactants and 0.01% (w/v) EDTA, retaining up to 80% of its activity. Additionally, we also found that Tk-SP can degrade PrPSc to a level undetectable by western-blot analysis. Conclusions Our results indicate that Tk-SP has a great potential for technological applications, such as thermo-stable detergent additives. In addition, it is also suggested that Tk-SP-containing detergents can be developed to decrease the secondary infection risks of transmissible spongiform encephalopathies (TSE). PMID:23448268

Peripheral Blood Signatures of Lead Exposure

PubMed Central

LaBreche, Heather G.; Meadows, Sarah K.; Nevins, Joseph R.; Chute, John P.

2011-01-01

Background Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. Methodology/Principal Finding Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. Conclusions/Significance The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway. PMID:21829687

Protein expression, characterization and activity comparisons of wild type and mutant DUSP5 proteins

DOE PAGES

Nayak, Jaladhi; Gastonguay, Adam J.; Talipov, Marat R.; ...

2014-12-18

Background: The mitogen-activated protein kinases (MAPKs) pathway is critical for cellular signaling, and proteins such as phosphatases that regulate this pathway are important for normal tissue development. Based on our previous work on dual specificity phosphatase-5 (DUSP5), and its role in embryonic vascular development and disease, we hypothesized that mutations in DUSP5 will affect its function. Results: In this study, we tested this hypothesis by generating full-length glutathione-S-transferase-tagged DUSP5 and serine 147 proline mutant (S147P) proteins from bacteria. Light scattering analysis, circular dichroism, enzymatic assays and molecular modeling approaches have been performed to extensively characterize the protein form and function.more » We demonstrate that both proteins are active and, interestingly, the S147P protein is hypoactive as compared to the DUSP5 WT protein in two distinct biochemical substrate assays. Furthermore, due to the novel positioning of the S147P mutation, we utilize computational modeling to reconstruct full-length DUSP5 and S147P to predict a possible mechanism for the reduced activity of S147P. Conclusion: Taken together, this is the first evidence of the generation and characterization of an active, full-length, mutant DUSP5 protein which will facilitate future structure-function and drug development-based studies.« less

Evidence for a reduced heparin cofactor II biological activity in diabetes.

PubMed

Ceriello, A; Quatraro, A; Dello Russo, P; Marchi, E; Milani, M R; Giugliano, D

1990-01-01

A reduction of heparin cofactor II (HCII) biological activity, despite its normal plasma concentration, is reported in insulin-dependent diabetic patients. A good linear correlation between HCII activity and concentration is present in normal controls but not in diabetics. In these subjects HCII activity correlates inversely with fasting blood glucose and glycated proteins but not with Hb A1. These data demonstrate the presence of a depressed HCII activity in the presence of its normal plasma concentration in insulin-dependent diabetics and suggest a role for short-term metabolic control in conditioning this phenomenon.

Identification of α-Chimaerin as a Candidate Gene for Critical Period Neuronal Plasticity in Cat and Mouse Visual Cortex

PubMed Central

2011-01-01

Background In cat visual cortex, critical period neuronal plasticity is minimal until approximately 3 postnatal weeks, peaks at 5 weeks, gradually declines to low levels at 20 weeks, and disappears by 1 year of age. Dark rearing slows the entire time course of this critical period, such that at 5 weeks of age, normal cats are more plastic than dark reared cats, whereas at 20 weeks, dark reared cats are more plastic. Thus, a stringent criterion for identifying genes that are important for plasticity in visual cortex is that they show differences in expression between normal and dark reared that are of opposite direction in young versus older animals. Results The present study reports the identification by differential display PCR of a novel gene, α-chimaerin, as a candidate visual cortex critical period plasticity gene that showed bidirectional regulation of expression due to age and dark rearing. Northern blotting confirmed the bidirectional expression and 5'RACE sequencing identified the gene. There are two alternatively-spliced α-chimaerin isoforms: α1 and α2. Western blotting extended the evidence for bidirectional regulation of visual cortex α-chimaerin isoform expression to protein in cats and mice. α1- and α2-Chimaerin were elevated in dark reared compared to normal visual cortex at the peak of the normal critical period and in normal compared to dark reared visual cortex at the nadir of the normal critical period. Analysis of variance showed a significant interaction in both cats and mice for both α-chimaerin isoforms, indicating that the effect of dark rearing depended on age. This differential expression was not found in frontal cortex. Conclusions Chimaerins are RhoGTPase-activating proteins that are EphA4 effectors and have been implicated in a number of processes including growth cone collapse, axon guidance, dendritic spine development and the formation of corticospinal motor circuits. The present results identify α-chimaerin as a candidate molecule for a role in the postnatal critical period of visual cortical plasticity. PMID:21767388

The Neural Substrates for Letter String Readings in The Normal and Reverse Directions: An fMRI Study

NASA Astrophysics Data System (ADS)

Ge, Sheng; Saito, Takashi; Wu, Jing-Long; Ogasawara, Jun-Ichi; Yamauchi, Shuichi; Matsunaga, Naofumi; Iramina, Keiji

In order to investigate the difference in cortical activations between reading letter strings in the normal direction and the reverse direction, an fMRI study was conducted. In this study, the cortical activations elicited by Japanese letter string reading and Chinese letter string reading were investigated. The subjects performed the normal direction reading task (read letter strings from left to right), and the reverse direction reading task (read letter strings from right to left). According to the experimental results, the activated brain regions during the normal and the reverse direction reading tasks were compared. It was found that visuospatial transformation was involved in the reverse direction reading task, while this function was not significant during the normal direction reading task. Furthermore, we found that there was no significant difference in cortical activation between Japanese and Chinese letter string readings.

Up-regulation of microglial cathepsin C expression and activity in lipopolysaccharide-induced neuroinflammation

PubMed Central

2012-01-01

Background Cathepsin C (Cat C) functions as a central coordinator for activation of many serine proteases in inflammatory cells. It has been recognized that Cat C is responsible for neutrophil recruitment and production of chemokines and cytokines in many inflammatory diseases. However, Cat C expression and its functional role in the brain under normal conditions or in neuroinflammatory processes remain unclear. Our previous study showed that Cat C promoted the progress of brain demyelination in cuprizone-treated mice. The present study further investigated the Cat C expression and activity in lipopolysaccharide (LPS)-induced neuroinflammation in vivo and in vitro. Methods C57BL/6 J mice were intraperitoneally injected with either 0.9% saline or lipopolysaccharide (LPS, 5 mg/kg). Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to analyze microglial activation, TNF-α, IL-1β, IL-6, iNOS mRNAs expressions and cellular localization of Cat C in the brain. Nitrite assay was used to examine microglial activation in vitro; RT-PCR and ELISA were used to determine the expression and release of Cat C. Cat C activity was analyzed by cellular Cat C assay kit. Data were evaluated for statistical significance with paired t test. Results Cat C was predominantly expressed in hippocampal CA2 neurons in C57BL/6 J mice under normal conditions. Six hours after LPS injection, Cat C expression was detected in cerebral cortical neurons; whereas, twenty-four hours later, Cat C expression was captured in activated microglial cells throughout the entire brain. The duration of induced Cat C expression in neurons and in microglial cells was ten days and three days, respectively. In vitro, LPS, IL-1β and IL-6 treatments increased microglial Cat C expression in a dose-dependent manner and upregulated Cat C secretion and its activity. Conclusions Taken together, these data indicate that LPS and proinflammatory cytokines IL-1β, IL-6 induce the expression, release and upregulate enzymatic activity of Cat C in microglial cells. Further investigation is required to determine the functional role of Cat C in the progression of neuroinflammation, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future. PMID:22607609